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Haehn N, Huehn M, Ralser M, Ziles D, Marx G, Mossanen JC, Schaefer B, Beier JP, Breuer T, Deininger MM. Impact of dysglycemia during the ebb and flow phases of critically ill burn patients: An observational study. Burns 2025; 51:107454. [PMID: 40096768 DOI: 10.1016/j.burns.2025.107454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 01/15/2025] [Accepted: 03/08/2025] [Indexed: 03/19/2025]
Abstract
BACKGROUND Critically ill burn patients face severe metabolic stress, divided into early ebb and late flow phases, causing dysglycemia. While detrimental effects of hyper- and hypoglycemia in burn patients have been reported over the entire stay, its impact during the ebb and flow phases remains unexplored. This study is the first to investigate phase-separated dysglycemia for outcome prediction. METHODS This retrospective, single-center observational study examined burn ICU patients between 2009 and 2022. Non-severe (ABSI<7) and severe (ABSI≥7) burn patients were investigated separately. Furthermore, the effect of low (<50 %) versus high (≥50 %) dysglycemic rates (<70 or >140 mg/dL) was evaluated within the ebb and flow phases. Dysglycemia was calculated using the time-unified rate, an innovative method representing blood glucose over time. The primary outcome of this study was mortality. RESULTS This study included 67 non-severe and 101 severe burn patients. During the flow compared to the ebb phase, non-severe burn patients showed increased hyperglycemic rates (>140 mg/dL, p = 0.027) and mean blood glucose levels (p = 0.003), while severe burn patients showed increased glycemic variability (p < 0.001) and hypoglycemic rates (<70 mg/dL, p = 0.003). Non-severe burn patients with high dysglycemic rates showed increased length of ICU stay (ebb: p = 0.029, flow: p = 0.040) and pneumonia incidence (ebb: p = 0.005, flow: p = 0.002) compared to patients with low dysglycemic rates. High dysglycemic rate was associated with higher mortality in severe burn patients (ebb: p = 0.027, flow: p = 0.008). Multivariate logistic regression revealed that hyper- (OR: 1.034, 95 %-CI: [1.001-1.068], p = 0.045) and hypoglycemic rates (OR: 1.744, 95 %-CI: [1.180-2.577], p = 0.005) during the flow, but not the ebb phase, predicted mortality in severe burn patients. CONCLUSIONS This study suggests that increased dysglycemic rate plays a relevant role in both non-severe and severe burn patients, with a varying impact. Over time, the flow phase was characterized by higher glycemic variability as well as hyper- and hypoglycemic rates, with the latter two predicting mortality in severe burn patients. While larger cohorts are needed to confirm these findings, the data indicate that reducing the dysglycemic rate, particularly during the flow phase, could improve outcomes in critically ill burn patients.
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Affiliation(s)
- Nico Haehn
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Marius Huehn
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Magdalena Ralser
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Dmitrij Ziles
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Gernot Marx
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Jana Christina Mossanen
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Benedikt Schaefer
- Department of Plastic Surgery, Hand Surgery - Burn Center, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Justus Patrick Beier
- Department of Plastic Surgery, Hand Surgery - Burn Center, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Thomas Breuer
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
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Zia-Ul-Sabah, Alqahtani SAM, Wani JI, Aziz S, Durrani HK, Patel AA, Rangraze I, Mirdad RT, Alfayea MA, Shahrani S. Stress hyperglycaemia ratio is an independent predictor of in-hospital heart failure among patients with anterior ST-segment elevation myocardial infarction. BMC Cardiovasc Disord 2024; 24:751. [PMID: 39732650 DOI: 10.1186/s12872-024-04362-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 11/18/2024] [Indexed: 12/30/2024] Open
Abstract
BACKGROUND Stress hyperglycaemia ratio (SHR) has been reported to be independently and significantly associated with various adverse cardiovascular events as well as mortality. Moreover, in-hospital heart failure following acute myocardial infarction has been demonstrated to account for majority of all heart failure (HF) cases with anterior myocardial infarction showing higher rates of HF. However, the association between SHR and in-hospital HF following an anterior ST-elevation myocardial infarction (STEMI) has not been reported earlier. Therefore, the present study aimed at identifying the relationship between SHR and in-hospital HF post STEMI. METHODS In this retrospective study electronic health records of 512 patients who presented with anterior STEMI from 01 January 2022 to 31 January 2024 were analysed. Based on the development of in-hospital HF, the enrolled patients were stratified into two groups: Group I, comprising of 290 patients who developed in-hospital HF and Group II comprising of 222 patients who did not develop in-hospital HF. ROC and Multivariable logistic regression analyses were performed to assess the relationship between SHR and in-hospital HF. RESULTS The results revealed that SHR is a significant independent predictor of in-hospital HF (OR: 3.53; 95%CI: 2.02-6.15; p < 0.001). Apart from SHR, the results also identified age, nosocomial pneumonia, ventricular fibrillation, LVEF, and NT-pro-BNP levels as other independent predictors. ROC analysis showed that SHR independently had a moderate discriminative power with AUC: 0.683, 95% CI 0.605-0.762; p = 0.04, which was almost comparable to the combined predictive value of other independent risk factors (AUC: 0.726, 95% CI 0.677-0.784). Noticeably, combining SHR and other identified independent predictors demonstrated a significant predictive power (AUC: 0.813, 95% CI 0.757-0.881; p = 0.01). CONCLUSION SHR is an independent predictor for in-hospital HF in anterior wall STEMI patients.
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Affiliation(s)
- Zia-Ul-Sabah
- Department of Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia.
- Prince Faisal bin Khalid Cardiac Centre, Abha, Saudi Arabia.
| | | | - Javed Iqbal Wani
- Department of Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Shahid Aziz
- Department of Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Humayoun Khan Durrani
- Department of Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Ayyub Ali Patel
- Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Imran Rangraze
- Department of Internal Medicine, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, UAE
| | - Rasha Tarek Mirdad
- Department of Surgery, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Muad Ali Alfayea
- Department of Medicine, Aseer Central Hospital, Abha, Saudi Arabia
| | - Sara Shahrani
- Prince Faisal bin Khalid Cardiac Centre, Abha, Saudi Arabia
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Ma C, Jiang W, Li J, Sun W, Zhang J, Xu P, Guo Y, Ning N, Li J, Zhao B, Mao E, Gao C. Association of Stress Hyperglycemia Ratio and in-Hospital Mortality in Patients with Sepsis: A Two Center Retrospective Cohort Study. J Inflamm Res 2024; 17:7939-7950. [PMID: 39494208 PMCID: PMC11531714 DOI: 10.2147/jir.s476898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 10/18/2024] [Indexed: 11/05/2024] Open
Abstract
INTRODUCTION In critically ill patients, the stress hyperglycemia ratio (SHR) was significantly associated with mortality. However, the relationship between SHR and mortality in septic patients is still unclear.In this study, patients with sepsis from two Chinese academic centers were identified and divided into quartiles based on SHR levels. METHODS Multivariable regression analysis will be used to determine associations between SHR and clinical outcomes in sepsis patients.The Kaplan-Meier curve was used to predict mortality in various groups of septic patients. RESULTS A total of 1835 septic patients were included in the study.The in-hospital, 30-day, and 60-day mortality rates for all septic patients were 22.8%, 18.7%, and 21.7%, respectively. Increased SHR was significantly associated with hospital mortality in multivariate regression analysis.These results were further confirmed in the adjusted analysis, where the hospital mortality and the 60-day mortality of the highest SHR quartile were significantly increased compared to the lowest SHR quartile. However, the highest SHR quartile was not associated with 30-day mortality.In addition, the risk of in-hospital mortality, 30-day mortality and 60-day mortality showed a consistent upward trend with increasing SHR quartile. The survival curve showed that the worst prognosis was in the fourth SHR quartile. DISCUSSION In conclusion, SHR was significantly associated with hospital mortality in patients with sepsis. This finding indicates that the SHR may be useful in identifying septic patients at higher risk of hospital mortality.
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Affiliation(s)
- Chaoping Ma
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
| | - Weisong Jiang
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Juan Li
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
| | - Wenwu Sun
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Jiyuan Zhang
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
| | - Peixian Xu
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
| | - Yiran Guo
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
| | - Ning Ning
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Jiaoyan Li
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Bing Zhao
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Enqiang Mao
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China
| | - Chengjin Gao
- Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China
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Yu C, Yao W, Liu K, Tang D. Serum glucose mediated association of serum lactate with acute kidney injury among AIS patients. Clin Biochem 2024; 131-132:110816. [PMID: 39222865 DOI: 10.1016/j.clinbiochem.2024.110816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 08/29/2024] [Accepted: 08/30/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND The serum lactate level has been confirmed to be an independent risk factor for the occurrence of acute kidney injury (AKI) in many diseases. However, the correlation between serum lactate level and AKI in critical patients with acute ischemic stroke (AIS) has not been clear. Moreover, limited studies have examined the mediating effect of serum glucose on the association between serum lactate and AKI. METHODS We identified 1,435 AIS patients from the Medical Information Mart for Intensive Care (MIMIC-III) database and divided them into AKI or No-AKI groups. We used a propensity score matching method to reduce confounding factors. Linear regression, logistic regression, and restricted cubic splines (RCS) plots were used to evaluate relationships between serum lactate levels and AKI. Finally, the mediating role of serum glucose on the relationship between serum lactate and AKI was investigated utilizing the mediation analysis. RESULTS In the present study, a total of 634 critical patients aged ≥ 18 years with AIS were included after propensity score matching (1:1). We used RCS plotting to reveal a linear association between serum lactate levels and AKI (P for nonlinearity < 0.001). After full adjustment for potential confounders (Model 3), high lactate levels increased the risk of AKI (odds ratio, 2.216; 95 % confidence interval, 1.559-3.271; P-value < 0.001). Serum glucose explained 14.9 % of the association between serum lactate and AKI among critical patients with AIS (P-value < 0.001), 16.4 % among patients with AIS and diabetes mellitus (DM) (P-value = 0.24), and 19.5 % among patients with AIS and without DM (P-value < 0.001). CONCLUSION Serum lactate was independently associated with increased risk-adjusted AKI in critical patients with AIS. The increase in serum glucose may have mediated this effect, especially in patients without DM.
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Affiliation(s)
- Chunli Yu
- Department of Nephrology, Jinshan Branch of Shanghai Sixth People's Hospital, Shanghai, China
| | - Weiguo Yao
- Department of Nephrology, Jinshan Branch of Shanghai Sixth People's Hospital, Shanghai, China
| | - Kun Liu
- Department of Nephrology, Jinshan Branch of Shanghai Sixth People's Hospital, Shanghai, China
| | - Dingzhong Tang
- Department of Neurology, Jinshan Branch of Shanghai Sixth People's Hospital, Shanghai, China.
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Shi RR, He TQ, Lin MS, Xu J, Gu JH, Xu H. O-GlcNAcylation in ischemic diseases. Front Pharmacol 2024; 15:1377235. [PMID: 38783961 PMCID: PMC11113977 DOI: 10.3389/fphar.2024.1377235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 04/15/2024] [Indexed: 05/25/2024] Open
Abstract
Protein glycosylation is an extensively studied field, with the most studied forms being oxygen or nitrogen-linked N-acetylglucosamine (O-GlcNAc or N-GlcNAc) glycosylation. Particular residues on proteins are targeted by O-GlcNAcylation, which is among the most intricate post-translational modifications. Significantly contributing to an organism's proteome, it influences numerous factors affecting protein stability, function, and subcellular localization. It also modifies the cellular function of target proteins that have crucial responsibilities in controlling pathways related to the central nervous system, cardiovascular homeostasis, and other organ functions. Under conditions of acute stress, changes in the levels of O-GlcNAcylation of these proteins may have a defensive function. Nevertheless, deviant O-GlcNAcylation nullifies this safeguard and stimulates the advancement of several ailments, the prognosis of which relies on the cellular milieu. Hence, this review provides a concise overview of the function and comprehension of O-GlcNAcylation in ischemia diseases, aiming to facilitate the discovery of new therapeutic targets for efficient treatment, particularly in patients with diabetes.
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Affiliation(s)
- Rui-Rui Shi
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Tian-Qi He
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
- Department of Pharmacy, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Meng-Si Lin
- Prenatal Screening and Diagnosis Center, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Jian Xu
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
- Department of Pharmacy, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Jin-Hua Gu
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
- Department of Pharmacy, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Hui Xu
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
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Xue Q, Ji S, Xu H, Yu S. O-GlcNAcylation: a pro-survival response to acute stress in the cardiovascular and central nervous systems. Eur J Med Res 2024; 29:174. [PMID: 38491477 PMCID: PMC10943874 DOI: 10.1186/s40001-024-01773-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 03/06/2024] [Indexed: 03/18/2024] Open
Abstract
O-GlcNAcylation is a unique monosaccharide modification that is ubiquitously present in numerous nucleoplasmic and mitochondrial proteins. The hexosamine biosynthesis pathway (HBP), which is a key branch of glycolysis, provides the unique sugar donor UDP-GlcNAc for the O-GlcNAc modification. Thus, HBP/O-GlcNAcylation can act as a nutrient sensor to perceive changes in nutrient levels and trigger O-GlcNAc modifications of functional proteins in cellular (patho-)physiology, thereby regulating diverse metabolic processes. An imbalance in O-GlcNAcylation has been shown to be a pathogenic contributor to dysfunction in metabolic diseases, including type 2 diabetes, cancer, and neurodegeneration. However, under acute stress conditions, protein O-GlcNAc modification exhibits rapid and transient upregulation, which is strongly correlated with stress tolerance and cell survival. In this context, we discuss the metabolic, pharmacological and genetic modulation of HBP/O-GlcNAc modification in the biological system, the beneficial role of O-GlcNAcylation in regulating stress tolerance for cardioprotection, and neuroprotection, which is a novel and rapidly growing field. Current evidence suggests that transient activation of the O-GlcNAc modification represents a potent pro-survival signalling pathway and may provide a promising strategy for stress-related disorder therapy.
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Affiliation(s)
- Qiu Xue
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, 226001, China
- Department of General Surgery, Nantong Tumor Hospital, Nantong Fifth People's Hospital, Affiliated Tumor Hospital of Nantong University, 30 Tongyang North Road, Nantong, 226361, China
| | - Shengtao Ji
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, 226001, China
- Department of Neurology, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Road, Nantong, 226001, China
| | - Hui Xu
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, 226001, China
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity & Child Healthcare Hospital of Nantong University, 399 Century Avenue, Nantong, 226001, China
| | - Shu Yu
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 19 Qixiu Road, Nantong, 226001, China.
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Kundu S, Tabassum S, Kumar RA, Abel ED, Kumar R. Plasmonic Optical Fiber Based Continuous in-Vivo Glucose Monitoring for ICU/CCU Setup. IEEE Trans Nanobioscience 2024; 23:157-166. [PMID: 37549091 DOI: 10.1109/tnb.2023.3303345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/09/2023]
Abstract
This paper reports a sensor architecture for continuous monitoring of biomarkers directly in the blood, especially for ICU/CCU patients requiring critical care and rapid biomarker measurement. The sensor is based on a simple optical fiber that can be inserted through a catheter into the bloodstream, wherein gold nanoparticles are attached at its far distal end as a plasmonic material for highly sensitive opto-chemical sensing of target biomolecules (glucose in our application) via the excitation of surface plasmon polaritons. For specificity, the nanoparticles are functionalized with a specific receptor enzyme that enables the localized surface plasmon resonance (LSPR)-based targeted bio-sensing. Further, a micro dialysis probe is introduced in the proposed architecture, which facilitates continuous monitoring for an extended period without fouling the sensor surface with cells and blood debris present in whole blood, leading to prolonged enhanced sensitivity and limit of detection, relative to existing state-of-the-art continuous monitoring devices that can conduct direct measurements in blood. To establish this proof-of-concept, we tested the sensor device to monitor glucose in-vivo involving an animal model, where continuous monitoring was done directly in the circulation of living rats. The sensor's sensitivity to glucose was found to be 0.0354 a.u./mg.dl-1 with a detection limit of 50.89 mg/dl.
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Liao W, Chen Y, Gao Q, Gan R, Li M, Liu Z, Liang J, Cui H, Ren K, Liu Y, Wang Z, Jiang J, Wei Q. Impact of stress hyperglycemia ratio, derived from glycated albumin or hemoglobin A1c, on mortality among ST-segment elevation myocardial infarction patients. Cardiovasc Diabetol 2023; 22:334. [PMID: 38057783 PMCID: PMC10701979 DOI: 10.1186/s12933-023-02061-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 11/10/2023] [Indexed: 12/08/2023] Open
Abstract
BACKGROUND Stress hyperglycemia ratio (SHR), associated with adverse outcomes in patients with ST-segment elevation myocardial infarction (STEMI), has several definitions. This study aims to assess the prognostic value of SHR, derived from hemoglobin A1c (HbA1c) or glycated albumin (GA), to mortality. METHODS The study comprised 1,643 STEMI patients who underwent percutaneous coronary intervention (PCI) in two centers. SHR1 was calculated using fasting blood glucose (FBG)/GA, while SHR2 was calculated using the formula FBG/(1.59*HbA1c-2.59). The primary endpoints were in-hospital death and all-cause mortality, with a median follow-up duration of 1.56 years. RESULTS Higher SHR1 and SHR2 values are associated with increased risks of in-hospital death and all-cause mortality. Each standard deviation increase in SHR1 corresponded to a 39% and 22% escalation in in-hospital death and all-cause mortality, respectively. The respective increases for SHR2 were 51% and 26%. Further examinations validated these relationships as linear. Additionally, the areas under the curve (AUC) for in-hospital death were not significantly different between SHR1 and SHR2 (p > 0.05). Incorporating SHR1 or SHR2 into the base model significantly improved the discrimination and risk reclassification for in-hospital and all-cause mortality. A subgroup analysis revealed that the effects of SHR1 and SHR2 were more pronounced in patients with hypercholesteremia. CONCLUSION SHR1 and SHR2 have emerged as robust and independent prognostic markers for STEMI patients undergoing PCI. The SHR calculation based on either HbA1c or GA can provide additional predictive value for mortality beyond traditional risk factors, helping to identify high-risk STEMI patients.
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Affiliation(s)
- Wang Liao
- Department of Cardiology, First People's Hospital of Yulin, Yulin, China
| | - Yuwen Chen
- Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qiyue Gao
- Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Rongrong Gan
- Department of Cardiology, First People's Hospital of Yulin, Yulin, China
| | - Ming Li
- Department of Cardiology, First People's Hospital of Yulin, Yulin, China
| | - Zhenliang Liu
- Department of Cardiology, First People's Hospital of Yulin, Yulin, China
| | - Jiasheng Liang
- Department of Cardiology, First People's Hospital of Yulin, Yulin, China
| | - Henghua Cui
- Department of Cardiology, First People's Hospital of Yulin, Yulin, China
| | - Kaida Ren
- Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yabin Liu
- Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhengdong Wang
- Department of Cardiology, First People's Hospital of Yulin, Yulin, China.
| | - Jun Jiang
- Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
| | - Qucheng Wei
- Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Xia W, Li C, Kuang M, Wu Y, Xu L, Hu H. Predictive value of glycemic gap and stress glycemia ratio among critically ill patients with acute kidney injury: a retrospective analysis of the MIMIC-III database. BMC Nephrol 2023; 24:227. [PMID: 37528371 PMCID: PMC10394760 DOI: 10.1186/s12882-023-03278-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 07/21/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND AND AIMS Acute hyperglycemia has been identified as a risk factor for acute kidney injury occurrence and mortality in various diseases. The aim of the current study was to investigate the relationship between stress-induced hyperglycemia and adverse outcomes in critically ill patients with AKI. METHODS We extracted clinical data from Multiparameter Intelligent Monitoring in Intensive Care III version 1.4. Blood glucose and glycosylated hemoglobin during the first 24 h of ICU admission were used to calculate glycemic gap and stress hyperglycemia ratio (SHR). The outcomes included ICU mortality and need for renal replacement therapy. The association of the glycemic gap and SHR with outcomes were determined via logistic regression model and receiver-operating curves. The subgroup analysis of patients with and without diabetes was performed separately. RESULTS Higher glycemic gap and SHR were observed in patients who had increased need of RRT, higher mortality rates and longer ICU stay. Multivariate analysis demonstrated that higher glycemic gap (OR 1.01, 95%CI 1.00-1.02, P = 0.015), as well as SHR (OR 1.32; 95%CI 1.07-1.64, P = 0.009), were independently associated with ICU mortality after adjusting for potential covariates. In subgroup analysis, the association of glycemic gap and SHR were only significant in the non-diabetic population as for the outcome of ICU mortality (OR 2.25, 95%CI 1.64-3.08, P < 0.001 and OR 1.99; 95%CI 1.46-2.72, P < 0.001, respectively). CONCLUSIONS The glycemic gap and SHR might serve as a potential prognostic indicator of ICU mortality in critically ill patients with AKI, especially in the non-diabetic population.
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Affiliation(s)
- Wenkai Xia
- Department of Nephrology, Jiangyin People's Hospital Affiliated to Nantong University, 3 Yingrui Road, Jiangsu, 214400, Jiangyin, China
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Chenyu Li
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Meisi Kuang
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Yu Wu
- Department of Nephrology, Jiangyin People's Hospital Affiliated to Nantong University, 3 Yingrui Road, Jiangsu, 214400, Jiangyin, China
| | - Lingyu Xu
- Department of Nephrology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Hong Hu
- Department of Nephrology, Jiangyin People's Hospital Affiliated to Nantong University, 3 Yingrui Road, Jiangsu, 214400, Jiangyin, China.
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Impact of catheter ablation and subsequent recurrence of atrial fibrillation on glucose status in patients undergoing continuous glucose monitoring. Sci Rep 2023; 13:4299. [PMID: 36922617 PMCID: PMC10017667 DOI: 10.1038/s41598-023-31139-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 03/07/2023] [Indexed: 03/18/2023] Open
Abstract
Although glucose metabolism and atrial fibrillation (AF) have complex interrelationships, the impact of catheter ablation of AF on glucose status has not been well evaluated. Continuous glucose monitoring (CGM) with a FreeStyle Libre Pro (Abbott) was performed for 48 h pre-procedure, during the procedure, and for 72 h post-procedure in 58 non-diabetes mellitus (DM) patients with symptomatic AF and 20 patients with supraventricular or ventricular arrhythmias as a control group. All ablation procedures including pulmonary vein isolation were performed successfully. Glucose levels during procedures consistently increased in the AF and control groups (83.1 ± 16.1 to 110.0 ± 20.5 mg/dL and 83.3 ± 14.7 to 98.6 ± 16.3 mg/dL, respectively, P < 0.001 for both), and Δ glucose levels (max minus min/procedure) were greater in the AF group than control group (P < 0.001). There was a trend toward higher mean glucose levels at 72 h after the procedures compared with those before the procedures in both the AF and control groups (from 103.4 ± 15.6 to 106.1 ± 13.0 mg/dL, P = 0.063 and from 100.2 ± 17.1 to 102.9 ± 16.9 mg/dL, P = 0.052). An acute increase in glucose level at the time of early AF recurrence (N = 9, 15.5%) could be detected by simultaneous CGM and ECG monitoring (89.7 ± 18.0 to 108.3 ± 30.5 mg/dL, P = 0.001). In conclusion, although AF ablation caused a statistically significant increase in the glucose levels during the procedures, it did not result in a pathologically significant change after ablation in non-DM patients. Simultaneous post-procedure CGM and ECG monitoring alerted us to possible acute increases in glucose levels at the onset of AF recurrence.
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Srinivasan V. Glucose Metabolism and Stress Hyperglycemia in Critically Ill Children. Indian J Pediatr 2023; 90:272-279. [PMID: 36645581 DOI: 10.1007/s12098-022-04439-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 11/13/2022] [Indexed: 01/17/2023]
Abstract
Abnormalities in glucose metabolism and stress hyperglycemia (SH) are commonly seen in critically ill children. While SH may represent an adaptive stress response as a source of fuel for the body during the "fight or flight response" of critical illness, several studies have observed the association of SH with worse outcomes in different disease states. In addition to alterations in glucose metabolism and acquired insulin resistance from inflammation and organ dysfunction, specific intensive care unit (ICU) interventions can also affect glucose homeostasis and SH during critical illness. Common ICU interventions can mediate the development of SH in critical illness. The strategy of tight glucose control combined with intensive insulin therapy (TGC-IIT) has been well studied to improve outcomes in both adult and pediatric critical illness. Though early single-center studies of TGC-IIT observed benefits with better outcomes albeit with greater incidence of hypoglycemia, subsequent larger multicenter studies in both children and adults have not conclusively demonstrated benefits and have even observed harm. Several possible reasons for these contrasting results include differences in patient populations, glycemic control targets, and glucose control protocols including nutrition support, and variability in achieving these targets, measurement methods, and expertise in protocol implementation. Future studies may need to individualize management of SH in critically ill children with improved monitoring of indices of glycemia utilizing continuous sensors and closed-loop insulin administration.
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Affiliation(s)
- Vijay Srinivasan
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA. .,Departments of Anesthesiology, Critical Care and Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
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12
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Cheong HS, Chang Y, Kim Y, Joo EJ, Kwon MJ, Wild SH, Byrne CD, Ryu S. Glycaemic status, insulin resistance, and risk of infection-related mortality: a cohort study. Eur J Endocrinol 2023; 188:7033310. [PMID: 36757815 DOI: 10.1093/ejendo/lvad011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 12/11/2022] [Accepted: 01/24/2023] [Indexed: 02/10/2023]
Abstract
IMPORTANCE The impact of non-diabetic hyperglycaemia and insulin resistance on infection-related mortality risk remains unknown. OBJECTIVE We investigated the association of glycaemic status and insulin resistance with infection-related mortality in individuals with and without diabetes. DESIGN Cohort study based on Kangbuk Samsung Health Study and national death records. PARTICIPANTS About 666 888 Korean adults who underwent fasting blood measurements including glucose, glycated haemoglobin (HbA1c), and insulin during health-screening examinations were followed for up to 15.8 years. MAIN OUTCOME AND MEASURES Infection-related mortality, therefore we used Cox proportional hazards regression analyses to estimate hazard ratios (HRs) and 95% CIs for infection-related mortality. Vital status and infection-related mortality were ascertained through national death records. Variable categories were created based on established cut-offs for glucose and HbA1c levels and homeostatic model assessment of insulin resistance (HOMA-IR) quintiles. RESULTS During a median follow-up of 8.3 years, 313 infectious disease deaths were dentified. The associations of glucose and HbA1c levels with infection-related mortality were J-shaped (P for quadratic trend<.05). The multivariable-adjusted HR (95% CIs) for infection-related mortality comparing glucose levels <5, 5.6-6.9, and ≥7.0 mmol/L to 5.0-5.5 mmol/L (the reference) were 2.31 (1.47-3.64), 1.65 (1.05-2.60), and 3.41 (1.66-7.00), respectively. Among individuals without diabetes, the multivariable-adjusted HR for infection-related mortality for insulin resistance (HOMA-IR ≥75th centile versus <75th centile) was 1.55 (1.04-2.32). CONCLUSIONS AND RELEVANCE Both low and high glycaemic levels and insulin resistance were independently associated with increased infection-related mortality risk, indicating a possible role of abnormal glucose metabolism in increased infection-related mortality.
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Affiliation(s)
- Hae Suk Cheong
- Division of Infectious Diseases, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 03181
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 03181
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 04514
- Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea, 06355
| | - Yejin Kim
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 03181
| | - Eun-Jeong Joo
- Division of Infectious Diseases, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 03181
| | - Min-Jung Kwon
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 03181
| | - Sarah H Wild
- Usher Institute, University of Edinburgh, Edinburgh, United Kingdom, EH8 9AG
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, SO16 6YD
- National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom, SO16 6YD
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 03181
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 04514
- Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea, 06355
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Swieszkowski SP, Costa D, Aladio JM, Matsudo M, Pérez de la Hoz A, Castro M, González D, Brignoli A, Pons S, Scazziota A, Pérez de la Hoz R. Neurohumoral response and stress hyperglycemia in myocardial infarction. J Diabetes Complications 2022; 36:108339. [PMID: 36345108 DOI: 10.1016/j.jdiacomp.2022.108339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 08/30/2022] [Accepted: 10/22/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Hyperglycemia is associated with an increased risk for death in acute coronary syndromes. This could be related to underlying glucose metabolism abnormalities or be caused by a counter-regulatory stress response. However, there is a paucity of data on the relationship between stress hormones, hyperglycemia, and clinical outcomes in myocardial infarction. METHODS Single-center, prospective, observational study. Patients admitted to the coronary care unit with a diagnosis of myocardial infarction were included. On admission, blood samples were obtained to measure serum glucose, cortisol, and catecholamines. A second sample was obtained at 8 AM after 48 h from admission. RESULTS There was a mild and positive correlation between serum cortisol and glucose (Spearman's rho = 0.24, p = 0.005), and no significant correlation was found between glucose and catecholamines. A similar correlation between cortisol and glucose among diabetics and non-diabetics was observed. Significantly higher serum cortisol and glucose levels were present in patients who developed heart failure or died during hospitalization. The association between glycemia and mortality lost significance in multivariate analysis, with a significant interaction term with cortisol (p = 0.003). CONCLUSION Cortisol is a key responsible for stress hyperglycemia, and its deleterious effects on the cardiovascular system could be the cause for worst outcomes associated with hyperglycemia in ACS. Further research is warranted to ascertain this relationship and to investigate potential therapeutic targets.
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Affiliation(s)
| | - Diego Costa
- Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Argentina.
| | - José Martín Aladio
- Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Argentina
| | - Maia Matsudo
- Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Argentina
| | - Alejo Pérez de la Hoz
- Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Argentina
| | - Marcela Castro
- Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Argentina
| | - Diego González
- Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Argentina
| | - Alejandra Brignoli
- Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Argentina
| | - Silvina Pons
- Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Argentina
| | - Alejandra Scazziota
- Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Argentina
| | - Ricardo Pérez de la Hoz
- Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Argentina
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Albloui F, John J, Alghamdi O, Alseraye F, Alqahtani A, Tamimi W, Albloshi A, Aldakheel FM, Mateen A, Syed R. Effect of hematocrit, galactose and ascorbic acid on the blood glucose readings of three point-of-care glucometers. Scand J Clin Lab Invest 2022; 82:563-570. [PMID: 36332153 DOI: 10.1080/00365513.2022.2138779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Glucometers are commonly used in a variety of healthcare settings and use in critically ill patients should not be assumed without appropriate tool validation. The study objective was to evaluate the accuracy of three point-of-care glucometers (POCGs) to assess glucose concentration in human blood sample. The POCGs tested included three different instruments and utilized three factors (hematocrit [Hct], galactose and ascorbic acid) in glucose measurements to determine the glucometers' accuracy and compared to the reference laboratory biochemical analyzer (Cobs 8000, Roche, Basal, Switzerland). In this study, the Nova StatStrip glucometer showed no significant variation compared to the laboratory method at high glucose level with various Hct%. ACCU-Chek Inform II overestimated the glucose results at Hct 22% and underestimated at Hct 62%. The Freestyle glucometer showed lower glucose levels compared to the Cobas 8000 at Hct 62%. The ACCU-Check showed significant increase of blood glucose with low Hct% levels when compared to the laboratory method. The Freestyle showed a decreased level of glucose with high Hct 62% interference compared to the Cobas 8000. Galactose interference 100 and 200 mg/dL dramatically affected the accuracy of ACCU-Chek Inform II. Nevertheless, among all three POCGs in this study, the Nova StatStrip showed the most reliable and stable results for glucose level in the presence of interference. Especially, those in critical care units, whereas the Freestyle Precision Pro and ACCU-Chek Inform II were insufficiently accurate for critically ill patients.
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Affiliation(s)
- Fawaz Albloui
- Department of Pathology and Laboratory Medicine, Security Forces Hospital Program, Riyadh, Saudi Arabia
| | - James John
- Department of Medical Laboratory Technology, School of Allied Health Science, Sathyabama Institute of Science and Technology, Chennai, India
| | - Osama Alghamdi
- Department of Pathology and Laboratory Medicine, Security Forces Hospital Program, Riyadh, Saudi Arabia
| | - Faisal Alseraye
- Department of Pathology and Laboratory Medicine, Kind Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
| | - Abdullah Alqahtani
- Department of Pathology and Laboratory Medicine, Security Forces Hospital Program, Riyadh, Saudi Arabia
| | - Waleed Tamimi
- Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, National Guard Health Affairs, Riyadh,Saudi Arabia
| | - Abdullah Albloshi
- Department of Anatomy, College of Medicine, Al Baha University, Al Bahah, Saudi Arabia
| | - Fahad M Aldakheel
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Ayesha Mateen
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Rabbani Syed
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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15
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Wang JH, Li H, Yang HK, Chen RD, Yu JS. Relationship between the mean of 24-h venous blood glucose and in-hospital mortality among patients with subarachnoid hemorrhage: A matched cohort study. Front Neurol 2022; 13:904293. [PMID: 35983431 PMCID: PMC9379100 DOI: 10.3389/fneur.2022.904293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 07/07/2022] [Indexed: 11/15/2022] Open
Abstract
Objective The aim of this study was to explore the correlation between the mean of 24-h venous blood glucose (BG) and in-hospital mortality and all-cause mortality (ACM) in patients with subarachnoid hemorrhage (SAH). Methods Detailed clinical information was acquired from the Medical Information Mart for Intensive IV (MIMIC-IV) database. The best cutoff value of mean BG was calculated using the X-tile program. Univariate and multivariate logistic regressive analyses were utilized to analyze the prognosis significance of mean BG, and survival curves were drawn using the Kaplan-Meier (K-M) approach. To improve the reliability of results and balance the impact of underlying confounders, the 1:1 propensity score matching (PSM) approach was utilized. Results An overall of 1,230 subjects were selected herein. The optimal cutoff value of the mean BG for in-hospital mortality was 152.25. In addition, 367 pairs of score-matched subjects were acquired after PSM analysis, and nearly all variables' differences were balanced. K-M analysis showed that patients with mean BG ≥ 152.25 mg/dl had significantly higher in-hospital, 3-month, and 6-month mortalities compared with patients with mean BG < 152.25 mg/dl (p < 0.001). The multivariable logistic regressive analyses revealed that patients with mean BG ≥ 152.25 mg/dl had significantly increased in-hospital mortality compared with patients with mean BG < 152.25 mg/dl after the adjustment for possible confounders (OR = 1.994, 95% CI: 1.321–3.012, p = 0.001). Similar outcomes were discovered in the PSM cohort. Conclusion Our data suggested that mean BG was related to ACM of patients with SAH. More studies are needed to further analyze the role of the mean of 24-h venous BG in patients with SAH.
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Schmitz T, Freuer D, Harmel E, Heier M, Peters A, Linseisen J, Meisinger C. Prognostic value of stress hyperglycemia ratio on short- and long-term mortality after acute myocardial infarction. Acta Diabetol 2022; 59:1019-1029. [PMID: 35532812 PMCID: PMC9242951 DOI: 10.1007/s00592-022-01893-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 04/09/2022] [Indexed: 01/08/2023]
Abstract
AIMS Prior studies demonstrated an association between hospital admission blood glucose and mortality in acute myocardial infarction (AMI). Because stress hyperglycemia ratio (SHR) has been suggested as a more reliable marker of stress hyperglycemia this study investigated to what extent SHR in comparison with admission blood glucose is associated with short- and long-term mortality in diabetic and non-diabetic AMI patients. METHODS The analysis was based on 2,311 AMI patients aged 25-84 years from the population-based Myocardial Infarction Registry Augsburg (median follow-up time 6.5 years [IQR: 4.9-8.1]). The SHR was calculated as admission glucose (mg/dl)/(28.7 × HbA1c (%)-46.7). Using logistic and COX regression analyses the associations between SHR and admission glucose and mortality were investigated. RESULT Higher admission glucose and higher SHR were significantly and nonlinearly associated with higher 28-day mortality in AMI patients with and without diabetes. In patients without diabetes, the AUC for SHR was significantly lower than for admission glucose (SHR: 0.6912 [95%CI 0.6317-0.7496], admission glucose: 0.716 [95%CI 0.6572-0.7736], p-value: 0.0351). In patients with diabetes the AUCs were similar for SHR and admission glucose. Increasing admission glucose and SHR were significantly nonlinearly associated with higher 5-year all-cause mortality in AMI patients with diabetes but not in non-diabetic patients. AUC values indicated a comparable prediction of 5-year mortality for both measures in diabetic and non-diabetic patients. CONCLUSIONS Stress hyperglycemia in AMI patients plays a significant role mainly with regard to short-term prognosis, but barely so for long-term prognosis, underlining the assumption that it is a transient dynamic disorder that occurs to varying degrees during the acute event, thereby affecting prognosis.
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Affiliation(s)
- T Schmitz
- Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany.
| | - D Freuer
- Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - E Harmel
- Department of Cardiology, Respiratory Medicine and Intensive Care, University Hospital Augsburg, Augsburg, Germany
| | - M Heier
- KORA Study Centre, University Hospital of Augsburg, Augsburg, Germany
- Institute for Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany
| | - A Peters
- Institute for Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany
- Chair of Epidemiology, Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - J Linseisen
- Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
- Independent Research Group Clinical Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany
| | - C Meisinger
- Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
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Wu Z, Liu L, Wang W, Cui H, Zhang Y, Xu J, Zhang W, Zheng T, Yang J. Triglyceride-glucose index in the prediction of adverse cardiovascular events in patients with premature coronary artery disease: a retrospective cohort study. Cardiovasc Diabetol 2022; 21:142. [PMID: 35906587 PMCID: PMC9338459 DOI: 10.1186/s12933-022-01576-8] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 07/16/2022] [Indexed: 12/12/2022] Open
Abstract
Background Premature coronary artery disease (PCAD) has become more common in recent years and is often associated with poor outcomes. Triglyceride-glucose (TyG) index is a simple and reliable surrogate for insulin resistance (IR) and is an independent predictor of cardiovascular prognosis. However, the prognostic value of the TyG index in patients with PCAD remains uncertain. Thus, this study aimed to investigate the prognostic value and predictive performance of the TyG index in patients with PCAD. Methods A total of 526 young subjects (male < 45 years, female < 55 years) with angiographically proven CAD from January 2013 to December 2018 were included consecutively in this study. Their clinical and laboratory parameters were collected, and the TyG index was calculated as \documentclass[12pt]{minimal}
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\begin{document}$$\mathrm{Ln}[\mathrm{fasting triglyceride }(\mathrm{TG}) (\mathrm{mg}/\mathrm{dL})\times \mathrm{fasting plasma glucose }(\mathrm{FPG}) (\mathrm{mg}/\mathrm{dL})/2]$$\end{document}Ln[fastingtriglyceride(TG)(mg/dL)×fastingplasmaglucose(FPG)(mg/dL)/2]. The follow-up time after discharge was 40–112 months (median, 68 months; interquartile range, 49‒83 months). The primary endpoint was the occurrence of the major adverse cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction (MI), coronary artery revascularization, and non-fatal stroke. Results The TyG index was significantly associated with traditional cardiovascular risk factors and the Gensini score (GS). Kaplan–Meier survival (MACE-free) curves by tertiles of the TyG index showed statistically significant differences (log-rank test, p = 0.001). In the fully adjusted Cox regression model, the Hazard ratio (95% CI) of MACE was 2.17 (1.15–4.06) in tertile 3 and 1.45 (1.11–1.91) for per SD increase in the TyG index. Time-dependent ROC analyses of the TyG for prediction of MACE showed the area under the curves (AUC) reached 0.631 at 3 years, 0.643 at 6 years, and 0.710 at 9 years. Furthermore, adding TyG index to existing risk prediction model could improve outcome prediction [C-statistic increased from 0.715 to 0.719, p = 0.007; continuous net reclassification improvement (NRI) = 0.101, p = 0.362; integrated discrimination improvement (IDI) = 0.011, p = 0.017]. Conclusion The TyG index is an independent predictor of MACE in patients with PCAD, suggesting that the TyG index has important clinical implications for risk stratification and early intervention of PCAD. Supplementary Information The online version contains supplementary material available at 10.1186/s12933-022-01576-8.
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Affiliation(s)
- Zhenguo Wu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Li Liu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Weiwei Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Huiliang Cui
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Yerui Zhang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Jiechang Xu
- Department of Cardiology, Boshan District Hospital, Zibo, China
| | - Wencheng Zhang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Tengfei Zheng
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Jianmin Yang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.
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Vedantam D, Poman DS, Motwani L, Asif N, Patel A, Anne KK. Stress-Induced Hyperglycemia: Consequences and Management. Cureus 2022; 14:e26714. [PMID: 35959169 PMCID: PMC9360912 DOI: 10.7759/cureus.26714] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/10/2022] [Indexed: 01/08/2023] Open
Abstract
Hyperglycemia during stress is a common occurrence seen in patients admitted to the hospital. It is defined as a blood glucose level above 180mg/dl in patients without pre-existing diabetes. Stress-induced hyperglycemia (SIH) occurs due to an illness that leads to insulin resistance and decreased insulin secretion. Such a mechanism causes elevated blood glucose and produces a complex state to manage with external insulin. This article compiles various studies to explain the development and consequences of SIH in the critically ill that ultimately lead to an increase in mortality while also discussing the dire impact of SIH on certain acute illnesses like myocardial infarction and ischemic stroke. It also evaluates multiple studies to understand the management of SIH with insulin and proper nutritional therapy in the hospitalized patients admitted to the Intensive care unit (ICU) alongside the non-critical care unit. While emphasizing the diverse effects of improper control of SIH in the hospital, this article elucidates and discusses the importance of formulating a discharge plan due to an increased risk of type 2 diabetes in the recovered.
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Affiliation(s)
- Deepanjali Vedantam
- Internal Medicine, Kamineni Academy of Medical Sciences and Research Centre, Hyderabad, IND
| | | | - Lakshya Motwani
- Research and Development, Smt. NHL (Nathiba Hargovandas Lakhmichand) Municipal Medical College, Ahmedabad, IND
| | - Nailah Asif
- Research, RAK (Ras Al Khaimah) College of Medical Sciences, Ras Al Khaimah, ARE
| | - Apurva Patel
- Research, GMERS (Gujarat Medical Education & Research Society) Gotri Medical College, Vadodara, IND
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Metabolic Response in Endothelial Cells to Catecholamine Stimulation Associated with Increased Vascular Permeability. Int J Mol Sci 2022; 23:ijms23063162. [PMID: 35328583 PMCID: PMC8950318 DOI: 10.3390/ijms23063162] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/07/2022] [Accepted: 03/12/2022] [Indexed: 02/07/2023] Open
Abstract
Disruption to endothelial cell homeostasis results in an extensive variety of human pathologies that are particularly relevant to major trauma. Circulating catecholamines, such as adrenaline and noradrenaline, activate endothelial adrenergic receptors triggering a potent response in endothelial function. The regulation of the endothelial cell metabolism is distinct and profoundly important to endothelium homeostasis. However, a precise catalogue of the metabolic alterations caused by sustained high catecholamine levels that results in endothelial dysfunction is still underexplored. Here, we uncover a set of up to 46 metabolites that exhibit a dose–response relationship to adrenaline-noradrenaline equimolar treatment. The identified metabolites align with the glutathione-ascorbate cycle and the nitric oxide biosynthesis pathway. Certain key metabolites, such as arginine and reduced glutathione, displayed a differential response to treatment in early (4 h) compared to late (24 h) stages of sustained stimulation, indicative of homeostatic metabolic feedback loops. Furthermore, we quantified an increase in the glucose consumption and aerobic respiration in endothelial cells upon catecholamine stimulation. Our results indicate that oxidative stress and nitric oxide metabolic pathways are downstream consequences of endothelial cell stimulation with sustained high levels of catecholamines. A precise understanding of the metabolic response in endothelial cells to pathological levels of catecholamines will facilitate the identification of more efficient clinical interventions in trauma patients.
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Liu X, Li D, Liu Z, Song Y, Zhang B, Zang Y, Zhang W, Niu Y, Shen C. Nicotinamide mononucleotide promotes pancreatic islet function through the SIRT1 pathway in mice after severe burns. Burns 2022; 48:1922-1932. [DOI: 10.1016/j.burns.2022.01.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 01/10/2022] [Accepted: 01/18/2022] [Indexed: 01/03/2023]
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Integration of Metabolomic and Clinical Data Improves the Prediction of Intensive Care Unit Length of Stay Following Major Traumatic Injury. Metabolites 2021; 12:metabo12010029. [PMID: 35050151 PMCID: PMC8780653 DOI: 10.3390/metabo12010029] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/22/2021] [Accepted: 12/24/2021] [Indexed: 12/23/2022] Open
Abstract
Recent advances in emergency medicine and the co-ordinated delivery of trauma care mean more critically-injured patients now reach the hospital alive and survive life-saving operations. Indeed, between 2008 and 2017, the odds of surviving a major traumatic injury in the UK increased by nineteen percent. However, the improved survival rates of severely-injured patients have placed an increased burden on the healthcare system, with major trauma a common cause of intensive care unit (ICU) admissions that last ≥10 days. Improved understanding of the factors influencing patient outcomes is now urgently needed. We investigated the serum metabolomic profile of fifty-five major trauma patients across three post-injury phases: acute (days 0–4), intermediate (days 5–14) and late (days 15–112). Using ICU length of stay (LOS) as a clinical outcome, we aimed to determine whether the serum metabolome measured at days 0–4 post-injury for patients with an extended (≥10 days) ICU LOS differed from that of patients with a short (<10 days) ICU LOS. In addition, we investigated whether combining metabolomic profiles with clinical scoring systems would generate a variable that would identify patients with an extended ICU LOS with a greater degree of accuracy than models built on either variable alone. The number of metabolites unique to and shared across each time segment varied across acute, intermediate and late segments. A one-way ANOVA revealed the most variation in metabolite levels across the different time-points was for the metabolites lactate, glucose, anserine and 3-hydroxybutyrate. A total of eleven features were selected to differentiate between <10 days ICU LOS vs. >10 days ICU LOS. New Injury Severity Score (NISS), testosterone, and the metabolites cadaverine, urea, isoleucine, acetoacetate, dimethyl sulfone, syringate, creatinine, xylitol, and acetone form the integrated biomarker set. Using metabolic enrichment analysis, we found valine, leucine and isoleucine biosynthesis, glutathione metabolism, and glycine, serine and threonine metabolism were the top three pathways differentiating ICU LOS with a p < 0.05. A combined model of NISS and testosterone and all nine selected metabolites achieved an AUROC of 0.824. Differences exist in the serum metabolome of major trauma patients who subsequently experience a short or prolonged ICU LOS in the acute post-injury setting. Combining metabolomic data with anatomical scoring systems allowed us to discriminate between these two groups with a greater degree of accuracy than that of either variable alone.
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Frezoulis PS, Oikonomidis IL, Saridomichelakis MN, Kasabalis D, Pappa A, Bouza-Rapti P, Chochlios T, Tsouloufi TK, Kritsepi-Konstantinou M, Soubasis N. Prevalence, association with systemic inflammatory response syndrome and outcome of stress hyperglycaemia in sick cats. J Small Anim Pract 2021; 63:197-202. [PMID: 34796970 DOI: 10.1111/jsap.13445] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 08/19/2021] [Accepted: 09/26/2021] [Indexed: 12/20/2022]
Abstract
OBJECTIVES To determine the prevalence of stress hyperglycaemia in sick cats, and to investigate the association of stress hyperglycaemia with systemic inflammatory response syndrome and outcome. MATERIALS AND METHODS Medical records (2004 to 2013) from sick cats admitted to the Medicine Unit of a Veterinary Teaching Hospital were retrospectively reviewed. Cases were enrolled if a serum glucose measurement and a complete medical record were available. Cats that were healthy, hypoglycaemic, diabetic, sedated or had a previous administration of drugs (apart from vaccination and deworming) were excluded. RESULTS The study included 647 cats; stress hyperglycaemia (serum glucose >8.3 mmol/L) was found in 194 (30%) cats, while 453 (70%) cats were normoglycaemic. The prevalence of systemic inflammatory response syndrome was significantly higher in cats with stress hyperglycaemia (25/174, 14.4%) compared to normoglycaemic cats (26/399, 6.5%). Significantly, more cats with stress hyperglycaemia were hospitalised [97/194 (50.0%)] compared to normoglycaemic cats [171/453 (37.7%)]. However, the median duration of hospitalisation was not significantly different [4 (1 to 26) days and 4 (1 to 24) days, respectively]. The prevalence of cats with negative outcome was not significantly different between the two groups (cats with stress hyperglycaemia: 37.1%, normoglycaemic cats: 33.9%). Nonetheless, when modelling of outcome prediction included breed, age, stress hyperglycaemia and disease category as factors, cats with stress hyperglycaemia had 2.8 times the odds to have a negative outcome (95% confidence interval: 1.3 to 6.4). CLINICAL SIGNIFICANCE Based on the cut-off employed in this study, Stress hyperglycaemia, as defined by the cut-off is common in sick cats. Stress hyperglycaemia is associated with systemic inflammatory response syndrome development and seem to be a negative prognostic indicator.
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Affiliation(s)
- P S Frezoulis
- Southfields Veterinary Specialists, Essex, SS15 6TP, UK
| | - I L Oikonomidis
- Faculty of Health Sciences, School of Veterinary Science, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
| | | | - D Kasabalis
- Faculty of Veterinary Science, University of Thessaly, 431 00, Karditsa, Greece
| | - A Pappa
- Faculty of Health Sciences, School of Veterinary Science, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
| | - P Bouza-Rapti
- Faculty of Health Sciences, School of Veterinary Science, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
| | - T Chochlios
- Faculty of Health Sciences, School of Veterinary Science, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
| | - T K Tsouloufi
- Faculty of Health Sciences, School of Veterinary Science, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
| | - M Kritsepi-Konstantinou
- Faculty of Health Sciences, School of Veterinary Science, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
| | - N Soubasis
- Faculty of Health Sciences, School of Veterinary Science, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
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Amino acids predict prognosis in patients with acute dyspnea. BMC Emerg Med 2021; 21:127. [PMID: 34717541 PMCID: PMC8557597 DOI: 10.1186/s12873-021-00519-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 10/19/2021] [Indexed: 11/13/2022] Open
Abstract
Background To identify amino acids that can predict risk of 90-day mortality in patients with acute dyspnea. Method Plasma levels of nine amino acids were analyzed 663 adult patients admitted to the Emergency Department (ED) with acute dyspnea. Cox proportional hazards models were used to examine the relation between amino acid levels and the risk of 90-day mortality. Result Eighty patients (12.1%) died within 90 days of admission. An “Amino Acid Mortality Risk Score” (AMRS), summing absolute plasma levels of glycine, phenylalanine and valine, demonstrated that among the patients belonging to quartile 1 (Q1) of the AMRS, only 4 patients died, compared to 44 patients in quartile 4. Using Q1 of the AMRS as reference, each increment of 1 SD in the AMRS was associated with a hazard ratio (HR) of 2.15 for 90-day mortality, and the HR was > 9 times higher in Q4. Conclusion Glycine, phenylalanine and valine are associated with a risk of 90-day mortality in patients admitted to the ED for acute dyspnea, suggesting that these amino acids may be useful in risk assessments.
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Abstract
BACKGROUND Stress-induced hyperglycemia is frequently experienced by critically ill patients and the use of glycemic control (GC) has been shown to improve patient outcomes. For model-based approaches to GC, it is important to understand and quantify model parameter assumptions. This study explores endogenous glucose production (EGP) and the use of a population-based parameter value in the intensive care unit context. METHOD Hourly insulin sensitivity (SI) was fit to clinical data from 145 patients on the Specialized Relative Insulin and Nutrition Titration GC protocol for at least 24 hours. Constraint of SI at a lower bound was used to explore likely EGP variability due to stress response. Minimum EGP was estimated during times when the model SI was constrained, and time and duration of events were examined. RESULTS Constrained events occur for 1.6% of patient hours. About 70% of constrained events occur in the first 12 hours and most events (~80%) occur when there is no exogenous nutrition given. Enhanced EGP values ranged from 1.16 mmol/min (current population value) to 2.75 mmol/min, with most being below 1.5 mmol/min (21% increase). CONCLUSION The frequency of constrained events is low and the current population value of 1.16 mmol/min is sufficient for more than 98% of patient hours, however, some patients experience significantly raised EGP probably due to an extreme stress response early in patient stay.
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Affiliation(s)
- Jennifer J. Ormsbee
- Department of Mechanical Engineering, Centre for Bioengineering, University of Canterbury, Christchurch, New Zealand
| | - Jennifer L. Knopp
- Department of Mechanical Engineering, Centre for Bioengineering, University of Canterbury, Christchurch, New Zealand
| | - J. Geoffrey Chase
- Department of Mechanical Engineering, Centre for Bioengineering, University of Canterbury, Christchurch, New Zealand
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Al-Yousif N, Rawal S, Jurczak M, Mahmud H, Shah FA. Endogenous Glucose Production in Critical Illness. Nutr Clin Pract 2021; 36:344-359. [PMID: 33682953 DOI: 10.1002/ncp.10646] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Regulation of endogenous glucose production (EGP) by hormonal, neuronal, and metabolic signaling pathways contributes to the maintenance of euglycemia under normal physiologic conditions. EGP is defined by the generation of glucose from substrates through glycogenolysis and gluconeogenesis, usually in fasted states, for local and systemic use. Abnormal increases in EGP are noted in patients with diabetes mellitus type 2, and elevated EGP may also impact the pathogenesis of nonalcoholic fatty liver disease and congestive heart failure. In this narrative review, we performed a literature search in PubMed to identify recently published English language articles characterizing EGP in critical illness. Evidence from preclinical and clinical studies demonstrates that critical illness can disrupt EGP through multiple mechanisms including increased systemic inflammation, counterregulatory hormone and catecholamine release, alterations in the hypothalamic-pituitary axis, insulin resistance, lactic acidosis, and iatrogenic insults such as vasopressors and glucocorticoids administered as part of clinical care. EGP contributes to hyperglycemia in critical illness when abnormally elevated and to hypoglycemia when abnormally depressed, each of which has been independently associated with increased mortality. Increased EGP may also promote protein catabolism that could worsen critical illness myopathy and impede recovery. Better understanding of the mechanisms and factors contributing to dysregulated EGP in critical illness may help in the development of therapeutic strategies that promote euglycemia, reduce intensive care unit-associated catabolism, and improve patient outcomes.
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Affiliation(s)
- Nameer Al-Yousif
- Department of Internal Medicine, UPMC Mercy Hospital, Pittsburgh, Pennsylvania, USA
| | - Sagar Rawal
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Michael Jurczak
- Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Hussain Mahmud
- Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Faraaz Ali Shah
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA
- Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Seichter F, Vogt J, Tütüncü E, Hagemann LT, Wachter U, Gröger M, Kress S, Radermacher P, Mizaikoff B. Metabolic monitoring via on-line analysis of 13C-enriched carbon dioxide in exhaled mouse breath using substrate-integrated hollow waveguide infrared spectroscopy and luminescence sensing combined with Bayesian sampling. J Breath Res 2021; 15:026013. [PMID: 33630755 DOI: 10.1088/1752-7163/ab8dcd] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
In studies that target specific functions or organs, the response is often overlaid by indirect effects of the intervention on global metabolism. The metabolic side of these interactions can be assessed based on total energy expenditure (TEE) and the contributions of the principal energy sources, carbohydrates, proteins and fat to whole body CO2 production. These parameters can be identified from indirect calorimetry using respiratory oxygen intake and CO2 dioxide production data that are combined with the response of the 13CO2 release in the expired air and the glucose tracer enrichment in plasma following a 13C glucose stable isotope infusion. This concept is applied to a mouse protocol involving anesthesia, mechanical respiration, a disease model, like hemorrhage and therapeutic intervention. It faces challenges caused by a small sample size for both breath and plasma as well as changes in metabolic parameters caused by disease and intervention. Key parameters are derived from multiple measurements, all afflicted with errors that may accumulate leading to unrealistic values. To cope with these challenges, a sensitive on-line breath analysis system based on substrate-integrated hollow waveguide infrared spectroscopy and luminescence (iHWG-IR-LS) was used to monitor gas exchange values. A Bayesian statistical model is developed that uses established equations for indirect calorimetry to predict values for respiratory gas exchange and tracer data that are consistent with the corresponding measurements and also provides statistical error bands for these parameters. With this new methodology, it was possible to estimate important metabolic parameters (respiratory quotient (RQ), relative contribution of carbohydrate, protein and fat oxidation fcarb, ffat and fprot , total energy expenditure TEE) in a resolution never available before for a minimal invasive protocol of mice under anesthesia.
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Affiliation(s)
- Felicia Seichter
- Institute of Analytical and Bioanalytical Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany
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Ubaid Ur Rahman H, Asghar W, Nazir W, Sandhu MA, Ahmed A, Khalid N. A comprehensive review on chlorpyrifos toxicity with special reference to endocrine disruption: Evidence of mechanisms, exposures and mitigation strategies. THE SCIENCE OF THE TOTAL ENVIRONMENT 2021; 755:142649. [PMID: 33059141 DOI: 10.1016/j.scitotenv.2020.142649] [Citation(s) in RCA: 120] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 09/24/2020] [Accepted: 09/24/2020] [Indexed: 04/15/2023]
Abstract
Chlorpyrifos (CPF) is a broad-spectrum chlorinated organophosphate (OP) pesticide used for the control of a variety of insects and pathogens in crops, fruits, vegetables, as well as households, and various other locations. The toxicity of CPF has been associated with neurological dysfunctions, endocrine disruption, and cardiovascular diseases (CVDs). It can also induce developmental and behavioral anomalies, hematological malignancies, genotoxicity, histopathological aberrations, immunotoxicity, and oxidative stress as evidenced by animal modeling. Moreover, eye irritation and dermatological defects are also reported due to CPF toxicity. The mechanism of action of CPF involves blocking the active sites of the enzyme, acetylcholinesterase (AChE), thereby producing adverse nervous system effects. Although CPF has low persistence in the body, its active metabolites, 3,5,6-trichloro-2-pyridinol (TCP), and chlorpyrifos-oxon (CPO) are comparatively more persistent, albeit equally toxic, and thus produce serious health complications. The present review has been compiled taking into account the work related to CPF toxicity and provides a brief compilation of CPF-induced defects in animals and humans, emphasizing the abnormalities leading to endocrine disruption, neurotoxicity, reproductive carcinogenesis, and disruptive mammary gland functionality. Moreover, the clinical signs and symptoms associated with the CPF exposure along with the possible pharmacological treatment are reported in this treatise. Additionally, the effect of food processing methods in reducing CPF residues from different agricultural commodities and dietary interventions to curtail the toxicity of CPF has also been discussed.
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Affiliation(s)
- Hafiz Ubaid Ur Rahman
- School of Food and Agricultural Sciences, University of Management and Technology, Lahore, Pakistan
| | - Waqas Asghar
- School of Food and Agricultural Sciences, University of Management and Technology, Lahore, Pakistan
| | - Wahab Nazir
- School of Food and Agricultural Sciences, University of Management and Technology, Lahore, Pakistan
| | - Mansur Abdullah Sandhu
- Department of Biomedical Sciences, Faculty of Veterinary & Animal Sciences, PMAS-Arid Agriculture University, Rawalpindi 46300, Pakistan
| | - Anwaar Ahmed
- Institute of Food and Nutrition Sciences, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46300, Pakistan
| | - Nauman Khalid
- School of Food and Agricultural Sciences, University of Management and Technology, Lahore, Pakistan.
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Idrovo JP, Shults JA, Curtis BJ, Chen MM, Kovacs EJ. Alcohol Intoxication and the Postburn Gastrointestinal Hormonal Response. J Burn Care Res 2020; 40:785-791. [PMID: 31102437 DOI: 10.1093/jbcr/irz083] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Gastrointestinal hormones are essential in postburn metabolism. Since near 50% of burn victims test positive for blood alcohol levels at hospital admission and have inferior outcomes compared to nonintoxicated burn patients; we hypothesized that the gastrointestinal hormone secretion is compromised in intoxicated burn victims. To test our theory, we quantified gastrointestinal hormones serum levels in a combine ethanol intoxication and burn injury mouse model. Thus, mice received a daily dose of ethanol for 3 days, rested 4 days, and were given ethanol 3 additional days. Mice underwent 15% TBSA scald burn 30 minutes after their last ethanol dose. Serum samples were collected 24 hours after burn injury. Nonintoxicated burned mice exhibited an increase in glucose, insulin, ghrelin, plasminogen activator inhibitor-1, leptin, and resistin by 1.4-, 3-, 13.5-, 6.2-, 9.4-, and 2.4-fold, respectively, compared to sham vehicle mice (P < .05). Burn injury also reduced serum gastric inhibitory polypeptide (GIP) by 32% compared to sham-injured, vehicle-treated mice. Leptin, resistin, glucagon-like peptide-1, as well as insulin, were not different from sham groups when intoxication preceded burn injury. Nevertheless, in burned mice treated with ethanol, gastric inhibitory polypeptide and glucagon serum levels exhibited a significant fold increase of 3.5 and 4.7, respectively. With these results, we conclude that 24 hours after burn injury, mice developed significant changes in gastrointestinal hormones, along with hyperglycemia. Moreover, the combined insult of burn and ethanol intoxication led to additional hormonal changes that may be attributed to a potential pancreatic dysfunction. Further multiday studies are required to investigate the etiology, behavior, and clinical significance of these hormonal changes.
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Affiliation(s)
- Juan-Pablo Idrovo
- Division of GI, Trauma and Endocrine Surgery, Department of Surgery, Burn Research and Alcohol Research Programs, University of Colorado, Denver, Aurora, Colorado
| | - Jill A Shults
- Department of Surgery, Alcohol Research Program, Loyola University Chicago, Maywood, Illinois
| | - Brenda J Curtis
- Division of GI, Trauma and Endocrine Surgery, Department of Surgery, Burn Research and Alcohol Research Programs, University of Colorado, Denver, Aurora, Colorado
| | - Michael M Chen
- Department of Surgery, Loyola University Chicago, Maywood, Illinois
| | - Elizabeth J Kovacs
- Division of GI, Trauma and Endocrine Surgery, Department of Surgery, Burn Research and Alcohol Research Programs, University of Colorado, Denver, Aurora, Colorado
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Schefold JC, Wollersheim T, Grunow JJ, Luedi MM, Z'Graggen WJ, Weber-Carstens S. Muscular weakness and muscle wasting in the critically ill. J Cachexia Sarcopenia Muscle 2020; 11:1399-1412. [PMID: 32893974 PMCID: PMC7749542 DOI: 10.1002/jcsm.12620] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 08/10/2020] [Accepted: 08/23/2020] [Indexed: 12/17/2022] Open
Affiliation(s)
- Joerg C Schefold
- Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Tobias Wollersheim
- Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Berlin Institute of Health (BIH), Berlin, Germany
| | - Julius J Grunow
- Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Berlin Institute of Health (BIH), Berlin, Germany
| | - Markus M Luedi
- Department of Anaesthesiology and Pain Medicine, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland
| | - Werner J Z'Graggen
- Department of Neurology and Neurosurgery, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland
| | - Steffen Weber-Carstens
- Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Berlin Institute of Health (BIH), Berlin, Germany
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Abstract
Physical trauma can affect any individual and is globally accountable for more than one in every ten deaths. Although direct severe kidney trauma is relatively infrequent, extrarenal tissue trauma frequently results in the development of acute kidney injury (AKI). Various causes, including haemorrhagic shock, rhabdomyolysis, use of nephrotoxic drugs and infectious complications, can trigger and exacerbate trauma-related AKI (TRAKI), particularly in the presence of pre-existing or trauma-specific risk factors. Injured, hypoxic and ischaemic tissues expose the organism to damage-associated and pathogen-associated molecular patterns, and oxidative stress, all of which initiate a complex immunopathophysiological response that results in macrocirculatory and microcirculatory disturbances in the kidney, and functional impairment. The simultaneous activation of components of innate immunity, including leukocytes, coagulation factors and complement proteins, drives kidney inflammation, glomerular and tubular damage, and breakdown of the blood-urine barrier. This immune response is also an integral part of the intense post-trauma crosstalk between the kidneys, the nervous system and other organs, which aggravates multi-organ dysfunction. Necessary lifesaving procedures used in trauma management might have ambivalent effects as they stabilize injured tissue and organs while simultaneously exacerbating kidney injury. Consequently, only a small number of pathophysiological and immunomodulatory therapeutic targets for TRAKI prevention have been proposed and evaluated.
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Woldaregay AZ, Launonen IK, Albers D, Igual J, Årsand E, Hartvigsen G. A Novel Approach for Continuous Health Status Monitoring and Automatic Detection of Infection Incidences in People With Type 1 Diabetes Using Machine Learning Algorithms (Part 2): A Personalized Digital Infectious Disease Detection Mechanism. J Med Internet Res 2020; 22:e18912. [PMID: 32784179 PMCID: PMC7450372 DOI: 10.2196/18912] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 06/06/2020] [Accepted: 06/11/2020] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND Semisupervised and unsupervised anomaly detection methods have been widely used in various applications to detect anomalous objects from a given data set. Specifically, these methods are popular in the medical domain because of their suitability for applications where there is a lack of a sufficient data set for the other classes. Infection incidence often brings prolonged hyperglycemia and frequent insulin injections in people with type 1 diabetes, which are significant anomalies. Despite these potentials, there have been very few studies that focused on detecting infection incidences in individuals with type 1 diabetes using a dedicated personalized health model. OBJECTIVE This study aims to develop a personalized health model that can automatically detect the incidence of infection in people with type 1 diabetes using blood glucose levels and insulin-to-carbohydrate ratio as input variables. The model is expected to detect deviations from the norm because of infection incidences considering elevated blood glucose levels coupled with unusual changes in the insulin-to-carbohydrate ratio. METHODS Three groups of one-class classifiers were trained on target data sets (regular days) and tested on a data set containing both the target and the nontarget (infection days). For comparison, two unsupervised models were also tested. The data set consists of high-precision self-recorded data collected from three real subjects with type 1 diabetes incorporating blood glucose, insulin, diet, and events of infection. The models were evaluated on two groups of data: raw and filtered data and compared based on their performance, computational time, and number of samples required. RESULTS The one-class classifiers achieved excellent performance. In comparison, the unsupervised models suffered from performance degradation mainly because of the atypical nature of the data. Among the one-class classifiers, the boundary and domain-based method produced a better description of the data. Regarding the computational time, nearest neighbor, support vector data description, and self-organizing map took considerable training time, which typically increased as the sample size increased, and only local outlier factor and connectivity-based outlier factor took considerable testing time. CONCLUSIONS We demonstrated the applicability of one-class classifiers and unsupervised models for the detection of infection incidence in people with type 1 diabetes. In this patient group, detecting infection can provide an opportunity to devise tailored services and also to detect potential public health threats. The proposed approaches achieved excellent performance; in particular, the boundary and domain-based method performed better. Among the respective groups, particular models such as one-class support vector machine, K-nearest neighbor, and K-means achieved excellent performance in all the sample sizes and infection cases. Overall, we foresee that the results could encourage researchers to examine beyond the presented features into other additional features of the self-recorded data, for example, continuous glucose monitoring features and physical activity data, on a large scale.
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Affiliation(s)
| | | | - David Albers
- Department of Pediatrics, Informatics and Data Science, University of Colorado, Aurora, CO, United States
- Department of Biomedical Informatics, Columbia University, New York, NY, United States
| | - Jorge Igual
- Universitat Politècnica de València, Valencia, Spain
| | - Eirik Årsand
- Department of Computer Science, University of Tromsø - The Arctic University of Norway, Tromsø, Norway
| | - Gunnar Hartvigsen
- Department of Computer Science, University of Tromsø - The Arctic University of Norway, Tromsø, Norway
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Abstract
Diseases of the pancreas vary by type, etiology, pathophysiology, and outcomes. One of the principle therapeutic considerations in all types of pancreatic diseases is nutrition. This review will consider acute pancreatitis (AP). Choice of patient, type and composition of nutrition, and timing of initiation will be discussed as components for achieving the maximum benefits of nutrition therapy in AP. The paradigm of nutrition therapy in AP has shifted to early enteral and/or oral nutrition based on disease severity to help mitigate the underlying inflammatory cascade of events leading to AP, beginning with anatomic and functional intestinal changes. Additionally, newer research investigating the inflammatory changes that instigate, maintain, and propagate AP will be discussed in terms of the nutrition effects on systemic inflammation. Nutrition therapy can mitigate the inflammatory changes in the intestinal tract and help with intestinal motility, bacterial overgrowth and translocation. It can help maintain intestinal bacterial composition and abundance similar to predisease levels. This review will also discuss the changes in the intestinal microbiome and effects of probiotics in AP.
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Affiliation(s)
- Amy E Murphy
- Department of Surgery, Division of Trauma/Acute Care Surgery/Critical Care, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Wauwatosa, WI, 53226, USA
| | - Panna A Codner
- Department of Surgery, Division of Trauma/Acute Care Surgery/Critical Care, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Wauwatosa, WI, 53226, USA
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Claudiano GS, Andrade SCS, Souza EC, Yunis-Aguinaga J, Coutinho LL, Moreira DKT, Gonçalves FC, Mundim AV, Marzocchi-Machado CM, de Moraes FR, Moraes JRE. Role of neuroendocrine modulation and biochemistry in the sepsis in Piaractus mesopotamicus. Gen Comp Endocrinol 2020; 288:113338. [PMID: 31812532 DOI: 10.1016/j.ygcen.2019.113338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 11/17/2019] [Indexed: 12/26/2022]
Abstract
Sepsis is a systemic process with multifactorial pathophysiology that affects most animal species. It is responsible for high rates of morbidity and mortality. This work aimed to study the biochemical and neuroendocrine changes of the sepsis process in Piaractus mesopotamicus after Aeromonas hydrophila inoculation analyzing changes in blood leukocyte and differences in neuroendocrine-biochemical modulation using RNA-seq. Fish showed hypercortisolemia, inhibition of glucose absorption, followed by hypocortisolemia and then hyperglycemia. Thyroid hormones (T3 and T4) showed immediate decrease in serum and T4 increased 6 h post-inoculation (HPI). Sepsis-induced hormonal alterations triggered changes in the metabolic pathways increasing protein and lipid catabolism, use of transient anaerobic glycolysis and liver injury. A reference transcriptome was constructed based on blood leukocytes from P. mesopotamicus. The assembly resulted in total 266,272 contigs with a N50 of 2786 bp. There was a reorganization of plasma membrane of leukocytes at the beginning of the septic process with increased expression of neuroendocrine receptors and with continuous flow of neurotransmitters, hormones and solutes with compensatory regulation at 6 HPI. Three and nine HPI seemed to be critical, the expression of a number of transcription factors was increased, including the modulatory DEGs related to glucocorticoid and thyroid hormones induced and suppressed (FDR < 0.05). Neuroendocrine modulation can regulate leukocytes and biochemical parameters of peripheral blood, being important sources for the study of the pathophysiology of sepsis. These finding highlights the importance of further studies focusing on biochemical-neuroendocrine changes in blood leukocytes and systemic sepsis.
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Affiliation(s)
- Gustavo S Claudiano
- Department of Veterinarian Pathology, Faculty of Agrarian and Veterinarian Sciences, São Paulo State University, Unesp, Jaboticabal, Brazil; Institute of Biodiversity and Forests, Federal University of Western Pará, UFOPA, Santarém, PA, Brazil.
| | - Sónia C S Andrade
- Department of Genetics and Evolutionary Biology, Institute of Biosciences, São Paulo University, USP, Brazil
| | - Elaine C Souza
- Educational Foundation of Penápolis, FUNEPE, Penápolis, São Paulo, Brazil
| | - Jefferson Yunis-Aguinaga
- Aquaculture Center of UNESP, Jaboticabal, São Paulo, Brazil; Instituto del Mar del Perú, IMARPE, Lima, Perú
| | - Luiz L Coutinho
- Department of Animal Science, São Paulo University, USP, ESALQ, Brazil
| | - Débora K T Moreira
- Institute of Biodiversity and Forests, Federal University of Western Pará, UFOPA, Santarém, PA, Brazil
| | - Felipe C Gonçalves
- Clinical Analysis Laboratory, Veterinary Hospital, Federal University of Uberlândia, UFU, Uberlândia, MG, Brazil
| | - Antonio V Mundim
- Clinical Analysis Laboratory, Veterinary Hospital, Federal University of Uberlândia, UFU, Uberlândia, MG, Brazil
| | - Cleni M Marzocchi-Machado
- Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, USP, Brazil
| | - Flávio R de Moraes
- Department of Veterinarian Pathology, Faculty of Agrarian and Veterinarian Sciences, São Paulo State University, Unesp, Jaboticabal, Brazil; Aquaculture Center of UNESP, Jaboticabal, São Paulo, Brazil
| | - Julieta R E Moraes
- Department of Veterinarian Pathology, Faculty of Agrarian and Veterinarian Sciences, São Paulo State University, Unesp, Jaboticabal, Brazil; Aquaculture Center of UNESP, Jaboticabal, São Paulo, Brazil.
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Khalfallah M, Abdelmageed R, Elgendy E, Hafez YM. Incidence, predictors and outcomes of stress hyperglycemia in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention. Diab Vasc Dis Res 2020; 17:1479164119883983. [PMID: 31726871 PMCID: PMC7510353 DOI: 10.1177/1479164119883983] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Stress hyperglycemia is a common finding during ST elevation myocardial infarction in diabetic patients and is associated with a worse outcome. However, there are limited data about stress hyperglycemia in non-diabetic patients and its outcome especially in patients undergoing primary percutaneous coronary intervention. METHODS The study was conducted on 660 patients with ST elevation myocardial infarction who were managed with primary percutaneous coronary intervention. Patients were classified into two groups according to the presence of stress hyperglycemia: group I (patients with stress hyperglycemia) and group II (patients without stress hyperglycemia). Patients were analysed for clinical outcome including mortality and the occurrence of major adverse cardiac events. RESULTS Incidence of stress hyperglycemia was 16.8%, multivariate regression analysis identified the independent predictors of stress hyperglycemia, that were family history of diabetes mellitus odds ratio 1.697 (95% confidence interval: 1.077-2.674, p = 0.023), body mass index >24 kg/m2 odds ratio 1.906 (95% confidence interval: 1.244-2.922, p = 0.003) and cardiogenic shock on admission odds ratio 2.517 (95% confidence interval: 1.162-5.451, p = 0.019). Mortality, cardiogenic shock, contrast induced nephropathy and no reflow phenomenon were significantly higher in stress hyperglycemia group with p value = 0.027, 0.001, 0.020 and 0.037, respectively. CONCLUSION Stress hyperglycemia in non-diabetic patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention is associated with increased incidence of no reflow phenomenon, contrast induced nephropathy, cardiogenic shock and higher mortality.
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Affiliation(s)
- Mohamed Khalfallah
- Department of Cardiovascular Medicine,
Tanta University, Tanta, Egypt
- Mohamed Khalfallah, Department of
Cardiovascular Medicine, Tanta University, 31 Elgeish Street, Tanta 31511,
Egypt.
| | - Randa Abdelmageed
- Department of Cardiovascular Medicine,
Tanta University, Tanta, Egypt
| | - Ehab Elgendy
- Department of Cardiovascular Medicine,
Tanta University, Tanta, Egypt
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Association of multiple glycemic parameters at intensive care unit admission with mortality and clinical outcomes in critically ill patients. Sci Rep 2019; 9:18498. [PMID: 31811218 PMCID: PMC6897941 DOI: 10.1038/s41598-019-55080-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 11/15/2019] [Indexed: 12/14/2022] Open
Abstract
The aim of the present study was to investigate the association of multiple glycemic parameters at intensive care unit (ICU) admission with outcomes in critically ill patients. Critically ill adults admitted to ICU were included prospectively in the study and followed for 180 days until hospital discharge or death. Patients were assessed for glycemic gap, hypoglycemia, hyperglycemia, glycemic variability, and stress hyperglycemia ratio (SHR). A total of 542 patients were enrolled (30% with preexisting diabetes). Patients with glycemic gap >80 mg/dL had increased need for renal replacement therapy (RRT; 37.7% vs. 23.7%, p = 0.025) and shock incidence (54.7% vs. 37.4%, p = 0.014). Hypoglycemia was associated with increased mortality (54.8% vs. 35.8%, p = 0.004), need for RRT (45.1% vs. 22.3%, p < 0.001), mechanical ventilation (MV; 72.6% vs. 57.5%, p = 0.024), and shock incidence (62.9% vs. 35.8%, p < 0.001). Hyperglycemia increased mortality (44.3% vs. 34.9%, p = 0.031). Glycemic variability >40 mg/dL was associated with increased need for RRT (28.3% vs. 14.4%, p = 0.002) and shock incidence (41.4% vs.31.2%, p = 0.039). In this mixed sample of critically ill subjects, including patients with and without preexisting diabetes, glycemic gap, glycemic variability, and SHR were associated with worse outcomes, but not with mortality. Hypoglycemia and hyperglycemia were independently associated with increased mortality.
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Sun YF, Song Y, Liu CS, Geng JL. Correlation between the glucose level and the development of acute pancreatitis. Saudi J Biol Sci 2019; 26:427-430. [PMID: 31485188 PMCID: PMC6717129 DOI: 10.1016/j.sjbs.2018.11.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 11/20/2018] [Accepted: 11/20/2018] [Indexed: 01/04/2023] Open
Abstract
Objective To investigate the correlation between the level of glucose in serum and the development of acute pancreatitis (AP). Methods Data of 153 AP cases were collected, in which there were 130 patients with mild AP (MAP), 4 with moderate-severe AP (MSAP) and 19 with severe AP (SAP). At the time of admission, following indexes of patients were recorded: glucose, APACHE II score, TNF-α and C-reaction protein (CRP). Results At the time of admission, the levels of glucose in serum and APACHE II scores in the MSAP and SAP groups were significantly higher than those in the MAP group, but after treatment, the level of glucose in serum was recovered in 95.8% of the patients in the MAP group, while this digit in the SAP group remained to be 68.4%; in the SAP group, the levels of TNF-α and CRP in patients with sustained hypertension were significantly higher than those with non-persistent hypertension; in terms of the length of stay in hospital, the SAP group was shorter than that in the non-treatment group, and the difference had statistical significance (p < 0.05). Moreover, we found that the level of glucose in serum was positively correlated with the APACHE II scores, TNF-α and CRP. Conclusion Glucose level in serum can be used as one of the indicators for evaluating the severity and development of AP in clinical practice.
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Affiliation(s)
- Yun-Fu Sun
- Department of Hepatobiliary Surgery, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai 264200, China
| | - Yu Song
- Department of Central Lab, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai 264200, China
| | - Chang-Sheng Liu
- The Second Department of General Surgery, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai 264200, China
| | - Jian-Li Geng
- Department of Hepatobiliary Surgery, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai 264200, China
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Cheung NW, Wong KYC, Kovoor P, McLean M. Stress hyperglycemia: A prospective study examining the relationship between glucose, cortisol and diabetes in myocardial infarction. J Diabetes Complications 2019; 33:329-334. [PMID: 30691725 DOI: 10.1016/j.jdiacomp.2018.12.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 12/20/2018] [Accepted: 12/27/2018] [Indexed: 01/08/2023]
Abstract
AIM We aimed to explore the relationship between stress, hyperglycemia and diabetes in myocardial infarction (MI), using serum cortisol as a surrogate marker for the severity of stress. METHODS Subjects with acute MI were prospectively recruited upon hospital admission. Serum glucose and cortisol were measured in addition to standard testing. Subjects were defined as having stress hyperglycemia (SH) if they had an admission glucose ≥7.8 mmol/L without a history of glucose intolerance. Subjects were followed up with glucose tolerance testing post-discharge. RESULTS Of the 200 subjects in the study, 58 had known diabetes/impaired glucose tolerance (IGT), and 45 had SH. There was a positive association between admission glucose and cortisol for the entire cohort (rs = 0.26, p < 0.01). This relationship was present in the subgroup who had SH and then normal glucose post-discharge (rs = 0.53, p = 0.03), but not in SH subjects who had diabetes/IGT on post-discharge testing. It was also evident amongst all subjects with normal glucose (rs = 0.46, p < 0.01), but not those with diabetes/IGT in general. On multivariate analysis, admission glucose was a positive predictor and cortisol a negative predictor of abnormal glucose tolerance. CONCLUSIONS Our data suggests that SH with MI reflects either underlying glucose intolerance or more severe stress in people without glucose intolerance.
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Affiliation(s)
- N Wah Cheung
- Dept of Diabetes & Endocrinology, Westmead Hospital, Hawkesbury Rd, Westmead, NSW 2145, Australia; University of Sydney, Camperdown, NSW 2006, Australia.
| | - K Y Carmen Wong
- Dept of Diabetes & Endocrinology, Westmead Hospital, Hawkesbury Rd, Westmead, NSW 2145, Australia; University of Sydney, Camperdown, NSW 2006, Australia
| | - Pramesh Kovoor
- Dept of Cardiology, Westmead Hospital, Hawkesbury Rd, Westmead, NSW 2145, Australia; University of Sydney, Camperdown, NSW 2006, Australia.
| | - Mark McLean
- Dept of Diabetes & Endocrinology, Blacktown Hospital, Blacktown 2148, Australia; Western Sydney University, Penrith, NSW 2751, Australia.
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Vihonen H, Kuisma M, Salo A, Ångerman S, Pietiläinen K, Nurmi J. Mechanisms of early glucose regulation disturbance after out-of-hospital cardiopulmonary resuscitation: An explorative prospective study. PLoS One 2019; 14:e0214209. [PMID: 30908518 PMCID: PMC6433228 DOI: 10.1371/journal.pone.0214209] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 03/10/2019] [Indexed: 01/18/2023] Open
Abstract
Background Hyperglycemia is common and associated with increased mortality after out-of-hospital cardiac arrest (OHCA) and return of spontaneous circulation (ROSC). Mechanisms behind ultra-acute hyperglycemia are not well known. We performed an explorative study to describe the changes in glucose metabolism mediators during the prehospital postresuscitation phase. Methods We included patients who were successfully resuscitated from out-of-hospital cardiac arrest in two physician-staffed units. Insulin, glucagon, and glucagon-like peptide 1 (GLP-1) were measured in prehospital and hospital admission samples. Additionally, interleukin-6 (IL-6), cortisol, and HbA1c were measured at hospital admission. Results Thirty patients participated in the study. Of those, 28 cases (71% without diabetes) had sufficient data for analysis. The median time interval between prehospital samples and hospital admission samples was 96 minutes (IQR 85–119). At the time of ROSC, the patients were hyperglycemic (11.2 mmol/l, IQR 8.8–15.7), with insulin and glucagon concentrations varying considerably, although mostly corresponding to fasting levels (10.1 mU/l, IQR 4.2–25.2 and 141 ng/l, IQR 105–240, respectively). GLP-1 increased 2- to 8-fold with elevation of IL-6. The median glucose change from prehospital to hospital admission was -2.2 mmol/l (IQR -3.6 to -0.2). No significant correlations between the change in plasma glucose levels and the changes in insulin (r = 0.30, p = 0.13), glucagon (r = 0.29, p = 0.17), or GLP-1 levels (r = 0.32, p = 0.15) or with IL-6 (r = (-0.07), p = 0.75), cortisol (r = 0.13, p = 0.52) or HbA1c levels (r = 0.34, p = 0.08) were observed. However, in patients who did not receive exogenous epinephrine during resuscitation, changes in blood glucose correlated with changes in insulin (r = 0.59, p = 0.04) and glucagon (r = 0.65, p = 0.05) levels, demonstrating that lowering glucose values was associated with a simultaneous lowering of insulin and glucagon levels. Conclusions Hyperglycemia is common immediately after OHCA and cardiopulmonary resuscitation. No clear hormonal mechanisms were observed to be linked to changes in glucose levels during the postresuscitation phase in the whole cohort. However, in patients without exogenous epinephrine treatment, the correlations between glycemic and hormonal changes were more obvious. These results call for future studies examining the mechanisms of postresuscitation hyperglycemia and the metabolic effects of the global ischemic insult and medical treatment.
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Affiliation(s)
- Hanna Vihonen
- Department of Emergency Medicine and Services, Päijät-Häme Central Hospital, Lahti, Finland
- Department of Emergency Medicine and Services, Helsinki University and Helsinki University Hospital, Helsinki, Finland
- * E-mail:
| | - Markku Kuisma
- Department of Emergency Medicine and Services, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | - Ari Salo
- Department of Emergency Medicine and Services, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | - Susanne Ångerman
- Department of Emergency Medicine and Services, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | - Kirsi Pietiläinen
- Obesity Research Unit, University of Helsinki and Endocrinology, Abdominal Center, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | - Jouni Nurmi
- Department of Emergency Medicine and Services, Helsinki University and Helsinki University Hospital, Helsinki, Finland
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Stewart KW, Chase JG, Pretty CG, Shaw GM. Nutrition delivery, workload and performance in a model-based ICU glycaemic control system. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2018; 166:9-18. [PMID: 30415721 DOI: 10.1016/j.cmpb.2018.09.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Revised: 08/20/2018] [Accepted: 09/10/2018] [Indexed: 06/09/2023]
Abstract
BACKGROUND AND OBJECTIVE Hyperglycaemia is commonplace in the adult intensive care unit (ICU), and has been associated with increased morbidity and mortality. Effective glycaemic control (GC) can reduce morbidity and mortality, but has proven difficult. STAR is a model-based GC protocol that uniquely maintains normoglycaemia by changing both insulin and nutrition interventions, and has been proven effective in controlling blood glucose (BG) in the ICU. However, most ICU GC protocols only change insulin interventions, making the variable nutrition aspect of STAR less clinically desirable. This paper compares the performance of STAR modulating only insulin, with three simpler alternative nutrition protocols in clinically evaluated virtual trials. METHODS Alternative nutrition protocols are fixed nutrition rate (100% caloric goal), CB (Cahill et al. best) stepped nutrition rate (60%, 80% and 100% caloric goal for the first 3 days of GC, and 100% thereafter) and SLQ (STAR lower quartile) stepped nutrition rate (65%, 75% and 85% caloric goal for the first 3 days of GC, and 85% thereafter). Each nutrition protocol is simulated with the STAR insulin protocol on a 221 patient virtual cohort, and GC performance, safety and total intervention workload are assessed. RESULTS All alternative nutrition protocols considerably reduced total intervention workload (14.6-19.8%) due to reduced numbers of nutrition changes. However, only the stepped nutrition protocols achieved similar GC performance to the current variable nutrition protocol. Of the two stepped nutrition protocols, the SLQ nutrition protocol also improved GC safety, almost halving the number of severe hypoglycaemic cases (5 vs. 9, P = 0.42). CONCLUSIONS Overall, the SLQ nutrition protocol was the best alternative to the current variable nutrition protocol, but either stepped nutrition protocol could be adapted by STAR to reduce workload and make it more clinically acceptable, while maintaining its proven performance and safety.
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Affiliation(s)
- Kent W Stewart
- Department of Mechanical Engineering, Centre for Bio-Engineering, University of Canterbury, Christchurch, New Zealand.
| | - J Geoffrey Chase
- Department of Mechanical Engineering, Centre for Bio-Engineering, University of Canterbury, Christchurch, New Zealand.
| | - Christopher G Pretty
- Department of Mechanical Engineering, Centre for Bio-Engineering, University of Canterbury, Christchurch, New Zealand.
| | - Geoffrey M Shaw
- Department of Intensive Care, Christchurch Hospital, Christchurch, New Zealand.
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Wesselink E, Koekkoek WAC, Grefte S, Witkamp RF, van Zanten ARH. Feeding mitochondria: Potential role of nutritional components to improve critical illness convalescence. Clin Nutr 2018; 38:982-995. [PMID: 30201141 DOI: 10.1016/j.clnu.2018.08.032] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 08/03/2018] [Accepted: 08/25/2018] [Indexed: 12/30/2022]
Abstract
Persistent physical impairment is frequently encountered after critical illness. Recent data point towards mitochondrial dysfunction as an important determinant of this phenomenon. This narrative review provides a comprehensive overview of the present knowledge of mitochondrial function during and after critical illness and the role and potential therapeutic applications of specific micronutrients to restore mitochondrial function. Increased lactate levels and decreased mitochondrial ATP-production are common findings during critical illness and considered to be associated with decreased activity of muscle mitochondrial complexes in the electron transfer system. Adequate nutrient levels are essential for mitochondrial function as several specific micronutrients play crucial roles in energy metabolism and ATP-production. We have addressed the role of B vitamins, ascorbic acid, α-tocopherol, selenium, zinc, coenzyme Q10, caffeine, melatonin, carnitine, nitrate, lipoic acid and taurine in mitochondrial function. B vitamins and lipoic acid are essential in the tricarboxylic acid cycle, while selenium, α-tocopherol, Coenzyme Q10, caffeine, and melatonin are suggested to boost the electron transfer system function. Carnitine is essential for fatty acid beta-oxidation. Selenium is involved in mitochondrial biogenesis. Notwithstanding the documented importance of several nutritional components for optimal mitochondrial function, at present, there are no studies providing directions for optimal requirements during or after critical illness although deficiencies of these specific micronutrients involved in mitochondrial metabolism are common. Considering the interplay between these specific micronutrients, future research should pay more attention to their combined supply to provide guidance for use in clinical practise. REVISION NUMBER: YCLNU-D-17-01092R2.
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Affiliation(s)
- E Wesselink
- Division of Human Nutrition and Health, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, The Netherlands.
| | - W A C Koekkoek
- Department of Intensive Care Medicine, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716, Ede, The Netherlands.
| | - S Grefte
- Human and Animal Physiology, Wageningen University, De Elst 1, 6708 DW, Wageningen, The Netherlands.
| | - R F Witkamp
- Division of Human Nutrition and Health, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, The Netherlands.
| | - A R H van Zanten
- Department of Intensive Care Medicine, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716, Ede, The Netherlands.
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Crossland H, Skirrow S, Puthucheary ZA, Constantin-Teodosiu D, Greenhaff PL. The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: different routes to similar end-points. J Physiol 2018; 597:1259-1270. [PMID: 29968251 PMCID: PMC6395472 DOI: 10.1113/jp275444] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Accepted: 05/16/2018] [Indexed: 01/04/2023] Open
Abstract
Loss of muscle mass and insulin sensitivity are common phenotypic traits of immobilisation and increased inflammatory burden. The suppression of muscle protein synthesis is the primary driver of muscle mass loss in human immobilisation, and includes blunting of post‐prandial increases in muscle protein synthesis. However, the mechanistic drivers of this suppression are unresolved. Immobilisation also induces limb insulin resistance in humans, which appears to be attributable to the reduction in muscle contraction per se. Again mechanistic insight is missing such that we do not know how muscle senses its “inactivity status” or whether the proposed drivers of muscle insulin resistance are simply arising as a consequence of immobilisation. A heightened inflammatory state is associated with major and rapid changes in muscle protein turnover and mass, and dampened insulin‐stimulated glucose disposal and oxidation in both rodents and humans. A limited amount of research has attempted to elucidate molecular regulators of muscle mass loss and insulin resistance during increased inflammatory burden, but rarely concurrently. Nevertheless, there is evidence that Akt (protein kinase B) signalling and FOXO transcription factors form part of a common signalling pathway in this scenario, such that molecular cross‐talk between atrophy and insulin signalling during heightened inflammation is believed to be possible. To conclude, whilst muscle mass loss and insulin resistance are common end‐points of immobilisation and increased inflammatory burden, a lack of understanding of the mechanisms responsible for these traits exists such that a substantial gap in understanding of the pathophysiology in humans endures.![]()
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Affiliation(s)
- Hannah Crossland
- MRC/Arthritis Research UK Centre for Musculoskeletal Ageing Research, Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, National Institute for Health Research Nottingham Biomedical Research Centre, School of Life Sciences, University of Nottingham, UK
| | - Sarah Skirrow
- MRC/Arthritis Research UK Centre for Musculoskeletal Ageing Research, Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, National Institute for Health Research Nottingham Biomedical Research Centre, School of Life Sciences, University of Nottingham, UK
| | - Zudin A Puthucheary
- Institute of Sport, Exercise and Health, London, UK.,Royal Free NHS Foundation Trust, London, UK
| | - Dumitru Constantin-Teodosiu
- MRC/Arthritis Research UK Centre for Musculoskeletal Ageing Research, Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, National Institute for Health Research Nottingham Biomedical Research Centre, School of Life Sciences, University of Nottingham, UK
| | - Paul L Greenhaff
- MRC/Arthritis Research UK Centre for Musculoskeletal Ageing Research, Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, National Institute for Health Research Nottingham Biomedical Research Centre, School of Life Sciences, University of Nottingham, UK
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Heidary Z, Khalili H, Mohammadi M, Beigmohammadi MT, Abdollahi A. Effect of Magnesium Loading Dose on Insulin Resistance in Patients With Stress-Induced Hyperglycemia: A Randomized Clinical Trial. J Intensive Care Med 2018; 35:687-693. [PMID: 29788815 DOI: 10.1177/0885066618777431] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVES There is currently no evidence that whether magnesium supplementation would improve stress-induced hyperglycemia (SIH) in critically ill patients. In this study, effects of magnesium loading dose on insulin resistance (IR) indices were evaluated in critically ill patients without diabetes having SIH. METHODS Seventy critically ill patients with SIH were assigned to receive a loading dose of magnesium (7.5 g of magnesium sulfate in 500 mL normal saline as intravenous infusion over an 8-hour period) or placebo. Changes in baseline of serum and intracellular magnesium and serum adiponectin (AD) levels, homeostasis model assessment of IR (HOMA-IR), and HOMA-AD ratio were assessed in this study. RESULTS Serum and intracellular magnesium levels increased significantly in patients in the magnesium group (P < .001). At day 3, there were significant differences between the magnesium group and the placebo group in the mean changes from baseline in the HOMA (between-group difference: -0.11; 95% confidence interval [CI]: -0.19 to -0.01; P = .02), the AD (between-group difference: 0.94; 95% CI: 0.41-1.48; P = .04), and the HOMA-AD ratio (between-group difference: -0.03; 95% CI: -0.04 to -0.01; P < .001). CONCLUSION In the present study, a single-loading dose of intravenous magnesium improved IR indices in critically ill patients with SIH.
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Affiliation(s)
- Zinat Heidary
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Khalili
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mostafa Mohammadi
- Department of Intensive Care Unit, Imam Khomeini Hospital, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad-Taghi Beigmohammadi
- Department of Intensive Care Unit, Imam Khomeini Hospital, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Abdollahi
- Department of Pathology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Thomas F, Dickson J, Pretty C, Stewart K, Fisk L, Shaw G, Chase JG. Accuracy and optimization of a subcutaneous insulin model for less acute critical care patients. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2018; 2015:4435-8. [PMID: 26737279 DOI: 10.1109/embc.2015.7319379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Extending safe, effective glycemic control to the general wards requires a simple approach using subcutaneous (SC) insulin. However, this approach can increase relative risk compared to intravenous insulin due to the increased variability of SC insulin appearance. This paper evaluates the accuracy of a SC plasma insulin model and optimizes its parameters using measured plasma insulin data from 6 less acute critical care patients treated with SC insulin. The SC plasma insulin model used captures the dynamics of regular SC insulin well. However, there appears to be a positive bias leading to an overall median [IQR] residual error of -28.3 [-37 - 19] mU/L. The optimized model reduced the RMS residual error by 20-70% for each patient. The distinct inter- and intra-patient, and cohort variation seen in this data highlights the importance to of understanding how SC insulin appearance dynamics may be affected by the subject condition.
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Ma J, Gao M, Pan R, He L, Zhao L, Liu J, Liu H. Hyperglycemia is associated with cardiac complications in elderly nondiabetic patients receiving total parenteral nutrition. Medicine (Baltimore) 2018; 97:e9537. [PMID: 29419661 PMCID: PMC5944667 DOI: 10.1097/md.0000000000009537] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Adverse outcomes have been associated with hyperglycemia in patients receiving total parenteral nutrition (TPN). The relationship may be characteristic in elderly patients. However, limited data are available about the relationship between TPN-related hyperglycemia and cardiac adverse outcome in elderly patients without previously known diabetes. This study aims to identify whether there is an association between hyperglycemia and 45-day cardiac adverse outcomes in critically and noncritically ill elderly nondiabetic patients receiving TPN.Outcome measures of 45-day cardiac complications after receiving TPN were recorded from a retrospective review of 1517 medical and surgical elderly patients. The mean glucose levels were significantly higher in patients with cardiac complications than in patients without cardiac complications (P < .001). In multivariate logistic regression analysis adjusting for age, gender, comorbidities, and medications, higher mean blood glucose levels were independently associated with increased 45-day cardiac complications (odds ratio, 1.62; 95% confidence interval, 1.453-1.816; P < .001). Furthermore, Kaplan-Meier event-free survival curves demonstrated that patients with mean blood glucose level ≥11.1 mmol/L had worse cardiac complications event-free survival compared with those mean blood glucose level <11.1 mmol/L during 45 days after receiving TPN.This study showed that TPN-induced hyperglycemia was associated with increased risk of cardiac complications in both critically and noncritically ill elderly patients without a history of diabetes.
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Affiliation(s)
| | - Meng Gao
- Department of Geriatric Cardiology
| | - Rong Pan
- Department of Geriatric Nephrology, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing
| | - Lei He
- Department of Neurology, Dancheng People's Hospital, Henan
| | - Lei Zhao
- Department of Endocrinology, Chinese PLA 305 Hospital
| | - Jie Liu
- Department of Emergency, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, China
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Stewart KW, Chase JG, Pretty CG, Shaw GM. Nutrition delivery of a model-based ICU glycaemic control system. Ann Intensive Care 2018; 8:4. [PMID: 29330610 PMCID: PMC5768573 DOI: 10.1186/s13613-017-0351-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 12/29/2017] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Hyperglycaemia is commonplace in the adult intensive care unit (ICU), associated with increased morbidity and mortality. Effective glycaemic control (GC) can reduce morbidity and mortality, but has proven difficult. STAR is a proven, effective model-based ICU GC protocol that uniquely maintains normo-glycaemia by changing both insulin and nutrition interventions to maximise nutrition in the context of GC in the 4.4-8.0 mmol/L range. Hence, the level of nutrition it provides is a time-varying estimate of the patient-specific ability to take up glucose. METHODS First, the clinical provision of nutrition by STAR in Christchurch Hospital, New Zealand (N = 221 Patients) is evaluated versus other ICUs, based on the Cahill et al. survey of 158 ICUs. Second, the inter- and intra- patient variation of nutrition delivery with STAR is analysed. Nutrition rates are in terms of percentage of caloric goal achieved. RESULTS Mean nutrition rates clinically achieved by STAR were significantly higher than the mean and best ICU surveyed, for the first 3 days of ICU stay. There was large inter-patient variation in nutrition rates achieved per day, which reduced overtime as patient-specific metabolic state stabilised. Median intra-patient variation was 12.9%; however, the interquartile range of the mean per-patient nutrition rates achieved was 74.3-98.2%, suggesting patients do not deviate much from their mean patient-specific nutrition rate. Thus, the ability to tolerate glucose intake varies significantly between, rather than within, patients. CONCLUSIONS Overall, STAR's protocol-driven changes in nutrition rate provide higher nutrition rates to hyperglycaemic patients than those of 158 ICUs from 20 countries. There is significant inter-patient variability between patients to tolerate and uptake glucose, where intra-patient variability over stay is much lower. Thus, a best nutrition rate is likely patient specific for patients requiring GC. More importantly, these overall outcomes show high nutrition delivery and safe, effective GC are not exclusive and that restricting nutrition for GC does not limit overall nutritional intake compared to other ICUs.
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Affiliation(s)
- Kent W. Stewart
- Department of Mechanical Engineering, Centre for Bio-Engineering, University of Canterbury, Private Bag 4800, Christchurch, 8140 New Zealand
| | - J. Geoffrey Chase
- Department of Mechanical Engineering, Centre for Bio-Engineering, University of Canterbury, Private Bag 4800, Christchurch, 8140 New Zealand
| | - Christopher G. Pretty
- Department of Mechanical Engineering, Centre for Bio-Engineering, University of Canterbury, Private Bag 4800, Christchurch, 8140 New Zealand
| | - Geoffrey M. Shaw
- Department of Intensive Care, Christchurch Hospital, Christchurch, New Zealand
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Srinivasan V. Nutrition Support and Tight Glucose Control in Critically Ill Children: Food for Thought! Front Pediatr 2018; 6:340. [PMID: 30460219 PMCID: PMC6232306 DOI: 10.3389/fped.2018.00340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 10/22/2018] [Indexed: 11/13/2022] Open
Abstract
Numerous studies have examined the strategy of tight glucose control (TGC) with intensive insulin therapy (IIT) to improve clinical outcomes in critically ill adults and children. Although early studies of TGC with IIT demonstrated improved outcomes at the cost of elevated hypoglycemia rates, subsequent studies in both adults and children have not demonstrated any benefit from such a strategy. Differences in patient populations, variable glycemic targets, and glucose control protocols, inconsistency in attaining these targets, heterogeneous intermittent sampling, and measurement techniques, and variable expertise in protocol implementation are possible reasons for the contrasting results from these studies. Notably, differences in modes of nutrition support may have also contributed to these disparate results. In particular, combined use of early parenteral nutrition (PN) and a strategy of TGC with IIT may be associated with improved outcomes, while combined use of enteral nutrition (EN) and a strategy of TGC with IIT may be associated with equivocal or worse outcomes. This article critically examines published clinical trials that have employed a strategy of TGC with IIT in critically ill children to highlight the role of EN vs. PN in influencing clinical outcomes including efficacy of TGC, and adverse effects such as occurrence of hypoglycemia and hospital acquired infections. The perspective afforded by this article should help practitioners consider the potential importance of mode of nutrition support in impacting key clinical outcomes if they should choose to employ a strategy of TGC with IIT in critically ill children with hyperglycemia.
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Affiliation(s)
- Vijay Srinivasan
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, United States.,Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
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Zhou T, Dickson JL, Geoffrey Chase J. Autoregressive Modeling of Drift and Random Error to Characterize a Continuous Intravascular Glucose Monitoring Sensor. J Diabetes Sci Technol 2018; 12:90-104. [PMID: 28707484 PMCID: PMC5761979 DOI: 10.1177/1932296817719089] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Continuous glucose monitoring (CGM) devices have been effective in managing diabetes and offer potential benefits for use in the intensive care unit (ICU). Use of CGM devices in the ICU has been limited, primarily due to the higher point accuracy errors over currently used traditional intermittent blood glucose (BG) measures. General models of CGM errors, including drift and random errors, are lacking, but would enable better design of protocols to utilize these devices. This article presents an autoregressive (AR) based modeling method that separately characterizes the drift and random noise of the GlySure CGM sensor (GlySure Limited, Oxfordshire, UK). METHODS Clinical sensor data (n = 33) and reference measurements were used to generate 2 AR models to describe sensor drift and noise. These models were used to generate 100 Monte Carlo simulations based on reference blood glucose measurements. These were then compared to the original CGM clinical data using mean absolute relative difference (MARD) and a Trend Compass. RESULTS The point accuracy MARD was very similar between simulated and clinical data (9.6% vs 9.9%). A Trend Compass was used to assess trend accuracy, and found simulated and clinical sensor profiles were similar (simulated trend index 11.4° vs clinical trend index 10.9°). CONCLUSION The model and method accurately represents cohort sensor behavior over patients, providing a general modeling approach to any such sensor by separately characterizing each type of error that can arise in the data. Overall, it enables better protocol design based on accurate expected CGM sensor behavior, as well as enabling the analysis of what level of each type of sensor error would be necessary to obtain desired glycemic control safety and performance with a given protocol.
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Affiliation(s)
- Tony Zhou
- Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand
- Tony Zhou, BE, Department of Mechanical Engineering, University of Canterbury, 20 Kirkwood Ave, Riccarton, Christchurch, Canterbury 8041, New Zealand.
| | - Jennifer L. Dickson
- Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand
| | - J. Geoffrey Chase
- Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand
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Langdon R, Docherty PD, Mansell EJ, Chase JG. Accurate and precise prediction of insulin sensitivity variance in critically ill patients. Biomed Signal Process Control 2018. [DOI: 10.1016/j.bspc.2017.08.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Zhou T, Dickson JL, Shaw GM, Chase JG. Continuous Glucose Monitoring Measures Can Be Used for Glycemic Control in the ICU: An In-Silico Study. J Diabetes Sci Technol 2018; 12:7-19. [PMID: 29103302 PMCID: PMC5761989 DOI: 10.1177/1932296817738791] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Continuous glucose monitoring (CGM) technology has become more prevalent in the intensive care unit (ICU), offering potential benefits of increased safety and reduced workload in glycemic control (GC). The drift and higher point accuracy errors of CGM devices over traditional intermittent blood glucose (BG) measures have so far limited their application in the ICU. This study delineates the trade-offs of performance, safety and workload that CGM sensors provide in GC protocols. METHODS Clinical data from 236 patients were used for clinically validated virtual trials. A CGM-enabled version of the STAR GC protocol was used to evaluate the use of guard rails and rolling windows. Safety was assessed through percentage of patients who had a severe hypoglycemic episode (BG < 40 mg/dl) as well as percentage of resampled BG < 72 mg/dl. Performance was assessed as percentage of resampled measurements in the 80-126 mg/dl and the 80-144 mg/dl target bands. Workload was measured by number of manual BG measures per day. RESULTS CGM-enabled versions of STAR decreased the number of required blood draws by up to 74%, while maintaining performance (76.6% BG measurements in the 80-126 mg/dl range vs 62.8% clinically, 87.9% in the 80-144 mg/dl range vs 83.7% clinically) and maintaining patient safety (1.13% of patients experienced a severe hypoglycemic event vs 0.85% clinically, 1.37% of BG measurements were less than 72 mg/dl vs 0.51% clinically). CONCLUSION CGM sensor traces were reproduced in virtual trials to guide GC. Existing GC protocols such as STAR may need to be adjusted only slightly to gain the benefits of the increased temporal measurements of CGM sensors, through which workload may be significantly decreased while maintaining GC performance and safety.
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Affiliation(s)
- Tony Zhou
- Department of Mechanical Engineering, University of Canterbury, Christchurch, Canterbury, New Zealand
- Tony Zhou, BE, Department of Mechanical Engineering, University of Canterbury, 20 Kirkwood Ave, Riccarton, Christchurch, Canterbury 8041, New Zealand.
| | - Jennifer L. Dickson
- Department of Mechanical Engineering, University of Canterbury, Christchurch, Canterbury, New Zealand
| | - Geoffrey M. Shaw
- Department of Intensive Care, Christchurch Hospital, Christchurch School of Medicine and Health Science, University of Otago, New Zealand
| | - J. Geoffrey Chase
- Department of Mechanical Engineering, University of Canterbury, Christchurch, Canterbury, New Zealand
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