To investigate the association between renal mean perfusion pressure (MPP) and prognosis in sepsis-associated acute kidney injury (SA-AKI).

Data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Group-based trajectory modeling (GBTM) was applied to identify dynamic MPP patterns, while restricted cubic spline (RCS) curves were utilized to confirm the non-linear relationship between MPP and mortality. Cox regression analysis assessed the risk of mortality across different MPP levels, adjusting for potential confounders. Subgroup analyses and sensitivity analyses were conducted to ensure the robustness of the findings.

A total of 2318 patients with SA-AKI were stratified into five MPP trajectories by GBTM. Patients in Traj-1 and Traj-2, characterized by consistently low MPP (<60 mmHg), demonstrated markedly higher 90-d mortality (62.86% and 26.98%). RCS curves revealed a non-linear inverse relationship between MPP and 90-d mortality, identifying 60 mmHg as the optimal threshold. Patients with MPP ≤ 60 mmHg exhibited significantly elevated 90-d mortality compared to those with MPP > 60 mmHg (29.81% vs. 20.88%). Cox regression analysis established Traj-1 and Traj-2 as independent risk factors for increased mortality relative to Traj-3 (60-70 mmHg), with hazard ratios (HRs) of 4.67 (95%-CI 3.28-6.67) and 1.45 (95%-CI 1.20-1.76). MPP > 60 mmHg was significantly associated with reduced 90-d mortality (HR 0.65, 95%-CI 0.55-0.77). Subgroup and PSM analyses supported these findings.

Dynamic MPP trajectory serves as a valuable prognostic biomarker for SA-AKI. Early monitoring of MPP trends offers critical insights into renal perfusion management, potentially improving outcomes in SA-AKI.

Septic shock necessitates timely antibiotic therapy, often with broad-spectrum beta-lactam antibiotics (ß-LA). To our knowledge, no previous study has examined antibiotic concentrations repeatedly during the initial phase of treatment. This observational study aimed to assess early-phase plasma concentrations of ß-LA in patients with septic shock.

Prospective observational study of patients with septic shock, according to the SEPSIS-3 criteria, who received cefotaxime, piperacillin/tazobactam, or meropenem in accordance with Swedish practice. Demographic and clinical data were recorded for each patient. Consecutive blood samples were obtained during the first 24 h of treatment, and total antibiotic concentrations were measured using liquid chromatography mass spectrometry. Target concentrations were defined as 100% of the time that free (unbound) antibiotic concentrations remained above the minimal inhibitory concentration (fT > MIC).

Twenty-two patients were included, 15 (68%) were male and the median age was 65.5 years (IQR 46.3-65.5). In-hospital mortality was 7/22 (32%). Antibiotic exposure exceeding 100% fT > MIC was achieved in 16 (73%) of the patients. Four patients did not receive the recommended additional dose between the first and second doses of antibiotics; two of them still achieved 100% fT > MIC, whereas the other two attained 66% and 33% fT > MIC, respectively. Among the patients who received the additional dose, four did not achieve 100% fT > MIC. No relationship between mortality and fT > MIC was observed. Significant associations with achieving 100% fT > MIC were observed for older age (p = 0.045) and illness severity (SAPS3, p = 0.025).

Our findings demonstrate considerable variability in antibiotic exposure during the initial 24 h of septic shock treatment, highlighting a critical gap in understanding the clinical relevance of sub-optimal serum antibiotic concentrations and their potential impact on patient outcomes.

Therapeutic drug monitoring of antimicrobials is increasingly being used in research and clinical practice.

Sepsis-induced systemic inflammatory responses can often lead to brain dysfunction with impaired cognitive function and mobility, known as sepsis-associated encephalopathy (SAE). Currently, there are no effective pharmacological therapeutics to treat SAE. Herein, we demonstrated the hexapeptide functionalized gold nanoparticles P12 that reduced SAE in septic mice with a dual mechanism to down-regulate systemic inflammation. We found that intraperitoneally administered P12 could target macrophages and regulate their inflammatory responses to decrease systemic inflammation and improve mice's cognitive function and mobility with SAE. Depleting peritoneal macrophages diminished the neuroprotective effects of P12 in SAE mice, suggesting macrophages as the effector cells for the neuroprotection by P12. In addition, the proteomic analysis revealed that P12 was capable of sequestering specific circulating inflammatory proteins in the blood of septic mice by forming a protein corona, contributing to the suppression of systemic inflammation. We also found that the local administration of P12 directly to the brain parenchyma effectively inhibited microglia activation and neuroinflammation in mice with SAE. This study provides an insightful understanding of the function and mechanisms of action of P12 in regulating sepsis-associated systemic inflammation and presents a new drug-free nanotherapeutic approach to treat SAE.

This review highlights the complex pathophysiology of myocardial dysfunction in septic shock and emphasizes the need for early and repeated hemodynamic assessments to improve outcome.

Septic cardiomyopathy is a complex, dynamic process driven by multiple mechanisms such as direct myocardial depression induced by host immune mediators (e.g., cytokines, nitric oxide) and/or bacterial toxins, and mitochondrial metabolic dysfunction. Recent echocardiography studies have described multiple unique hemodynamic clusters (phenotypes) that correlated with clinical outcomes. Similarly, serial echocardiography findings and mean arterial pressure abnormalities in patients with Streptococcal Toxic Shock Syndrome (StrepTSS) yielded three distinct hemodynamic groups that predicted mortality and morbidity. Because excessive use of fluids and/or vasopressors can be detrimental, especially in patients with microvascular injury or cardiomyopathy, application of the cardiovascular performance criteria of these different phenotypes could better inform management decisions in real time and improve outcome.

Septic cardiomyopathy is a dynamic, multidimensional response of the myocardium to infection involving both normal and dysregulated immune responses in which the measurable changes in myocardial function predict outcomes. This current paradigm mandates that functional parameters of cardiac performance be measured early and repeatedly throughout the disease course using echocardiography to guide treatment and improve outcome.

Early fluid resuscitation is crucial in the treatment of sepsis, yet the optimal dosage remains debated. This study aims to determine the optimal multi-stage fluid resuscitation dosage for sepsis patients.

We propose a reinforcement learning algorithm with neural networks (RL-NN), utilizing the flexibility of deep learning architectures to mitigate model misspecification. We use cross-validation and random search for hyperparameter tuning to further enhance model robustness and generalization.

Simulation results demonstrate that our method outperforms existing methods in terms of both the percentage of correctly classified optimal treatments and the predicted counterfactual mean outcome. Applying this method to the sepsis cohort from the Medical Information Mart for Intensive Care III (MIMIC-III), we recommend that all sepsis patients receive adequate fluid resuscitation (≥ 30 mL/kg) within the first 3 h of admission to the MICU. Our approach is expected to significantly reduce the mean SOFA score by 23.71%, enhancing patient outcomes.

Our RL-NN method offers an accurate, real-time approach to optimizing sepsis treatment and aligns with the 'Surviving Sepsis Campaign' guidelines. It also has the potential to be integrated with existing electronic health record (EHR) systems, guiding clinical decision-making and thereby improving patient prognosis.

Background: Dynamic assessment of cardiac output (CO) with passive leg raise (PLR), stroke volume variation (SVV), and pulse pressure variation (PPV) offer effective and safe methods to predict fluid responsiveness in patients with shock. The primary aim of this study was to evaluate the reliability of CO and SVV readings with the ultrasonic cardiac output monitor (USCOM) 1A device compared to PPV measurements in determining fluid responsiveness of patients in shock. Materials and Method: Intubated and mechanically ventilated patients aged 18-95 with shock admitted to the medical intensive care unit from June 2019 to December 2020 were included in the study. Fluid responsiveness was assessed using PPV from arterial monitoring and CO/SVV using the USCOM 1A device. CO, PPV, and SVV data were recorded before and after PLR. Results: Out of 145 shock patients, 92 were included. Before the PLR maneuver, 67 patients had PPV values above 12% and were stated as fluid responsive. The SVV index measured by the USCOM device demonstrated good sensitivity (85%) and specificity (96%) in identifying fluid responsiveness. The agreement with PPV was substantial (Cronbach's alpha reliability: 0.718 [ P < 0.001]), and the index was internally consistent (kappa agreement: 0.707 [ P < 0.001]). The SVV index moderately correlated with PPV (R: 0.588 [ P = 0.001]). Regarding fluid responsiveness determined by PPV, the AUC value of SVV was 0.797 (0.701-0.894) (p: 0.001). Conclusion: SVV measured by the USCOM device is a reliable and practical tool for hemodynamic assessment in clinical practice, particularly when invasive methods are unsuitable.

Sepsis is a dysregulated host response to infection with high mortality and morbidity. Early detection and intervention have been shown to improve patient outcomes, but existing computational models relying on structured electronic health record data often miss contextual information from unstructured clinical notes. This study introduces COMPOSER-LLM, an open-source large language model (LLM) integrated with the COMPOSER model to enhance early sepsis prediction. For high-uncertainty predictions, the LLM extracts additional context to assess sepsis-mimics, improving accuracy. Evaluated on 2500 patient encounters, COMPOSER-LLM achieved a sensitivity of 72.1%, positive predictive value of 52.9%, F-1 score of 61.0%, and 0.0087 false alarms per patient hour, outperforming the standalone COMPOSER model. Prospective validation yielded similar results. Manual chart review found 62% of false positives had bacterial infections, demonstrating potential clinical utility. Our findings suggest that integrating LLMs with traditional models can enhance predictive performance by leveraging unstructured data, representing a significant advance in healthcare analytics.

Accurate and rapid antimicrobial susceptibility test (AST) results from positive blood cultures are crucial for patient care and combatting antimicrobial resistance. Although recent advancements in rapid direct-from-positive blood culture (PBC) identification platforms have enabled the provision of species-level identification and some resistance marker information within hours after blood culture positivity, AST results required for clinical decision-making often require 48 h after blood culture positivity. This study evaluated the Selux next-generation phenotyping system, including an automated PBC Separator and the Selux AST system in a multicenter clinical trial for their ability to perform AST directly from PBCs for gram-negative bacilli. The PBC separator produces McFarland equivalent inocula from positive blood cultures within 1 h, facilitating direct processing on the Selux AST system. The study evaluated 162 fresh clinical PBC samples, 307 seeded clinical samples, and 87 seeded challenge samples across 4 sites for each of the 17 antimicrobials included in the panel. The results demonstrate that the Selux system's clinical performance, reproducibility, and analytical performances are consistent when using positive blood cultures held for up to 16 h after positivity on the BACTEC and BacT/ALERT 3D and BacT/ALERT VIRTUO blood culture systems, including all major BACTEC and BacT/ALERT blood culture bottle types. These findings suggest that the PBC Separator with the Selux AST system is a valuable addition to the arsenal of tools available for rapid sepsis diagnosis and management.IMPORTANCETechnologies that consistently and substantially shorten the time between blood bottle positivity, organism identification, and complete AST results are crucial for ensuring that antimicrobial therapy can be tailored. The Selux PBC Separator and the Selux AST system perform rapid AST directly from positive blood culture bottles. This substantially shortens the gap between obtaining a positive blood bottle and organism identification and the availability of a fully actionable AST result.

Norepinephrine (NE) is a first line and effective vasopressor for septic shock management, but its impact on newonset acute kidney injury (AKI) in those patients remains controversial. This study sought to investigate the relationship between norepinephrine dose trajectories and the new occurrence of AKI during the management of septic shock by using NE.

A retrospective cohort study was conducted using the MIMIC-IV database, which includes 3,462 patients diagnosed with septic shock during the initial 96 hours following their admission to the ICU. The unique patterns of trajectory analysis of NE were characterized by using group-based trajectory modeling (GBTM) during the initial four days of ICU admission. We employed multivariable logistic regression analysis and subgroup analysis to evaluate the association between NE dose trajectories and new-onset AKI in patients with septic shock.

Three NE dose trajectories were identified: low NE dose (47.3%), middle NE dose (41.5%), and high NE dose (11.2%). The high NE dose trajectory had significantly higher risks for new onset of AKI (OR 2.39, 95% CI 1.43-3.99), MAKE-30 (OR 3.82, 95% CI 2.97-4.91), and for 28-day mortality (HR 2.01, 95% CI 1.70-2.37) compared to the low NE dose trajectory. Despite over 90% of patients in the middle NE dose trajectory developing AKI, patients in this trajectory exhibited a lower risk of MAKE-30 and 28-day mortality. After comprehensive adjustment for demographic characteristics, comorbidities, acute physiological status, laboratory indicators, and fluid management, high NE dose trajectory remained independently associated with increased risk of new-onset AKI (OR 1.39, 95% CI 1.04-1.86, P = 0.024), this association persisted across multiple subgroup analyses.

During the management of septic shock, high dose of NE trajectory was associated with high likelihood of new onset of AKI, high possibility of MAKE-30 and high 28-day mortality in patients with septic shock. High NE dose trajectory serves as an independent predictor for assessing the risk of new-onset AKI in patients with septic shock.

Trauma-related injuries account for up to 4.4 million deaths annually worldwide. Failure to identify haemorrhage in trauma patients increases mortality. This study examines the association of central capillary refill time (CRT) and mortality in adult trauma patients, especially in the subgroup with normal heart rate (HR) and blood pressure (BP).

This retrospective observational study analysed data from the CRASH-2 trial, conducted in 274 hospitals across 40 countries and 5 continents between May 2005 and January 2010. A total of 19,054 out of 20,207 adult trauma patients with recorded CRT and complete dataset were included. CRT was taken centrally (sternum) and categorized as ≤ 2, 3-4, and ≥ 5 s. The primary outcome was 28-day mortality, while secondary outcomes included need for transfusion, surgical intervention and thromboembolic events. Univariable and multivariable logistic regression analysis were conducted, incorporating random effects for continent/cluster. Receiver operating characteristic curves were used to assess the discriminatory ability of central CRT measurement.

Among the patients, 6,756 (35.5%) had a CRT ≤ 2 s, 9,142 (48%) had a CRT of 3-4 s, and 3,156 (16.6%) had a CRT ≥ 5 s. Compared to the reference category (CRT ≤ 2 s), the odds of death were significantly higher in patients with CRT of 3-4 s (OR 1.7, 95% CI 1.6-1.9) and CRT ≥ 5 s (OR 3.2, 95% CI 2.8-3.5). Higher CRT was also associated with an increased likelihood of blood transfusion, surgical intervention, and thromboembolic events. The AUC values ranged from 0.63 to 0.74 and were consistent with a significant association between the variables.

Central CRT is associated with increased mortality and adverse outcomes in trauma patients. In bleeding trauma patients, an increasing central CRT is linked to higher mortality risk, with a central CRT ≥ 5 s being particularly predictive of worse outcomes. This also applies to patients with stable vital signs (normal HR and BP), suggesting that CRT may offer additional value as an indicator of hidden hypoperfusion.

Sepsis is a life-threatening condition resulting from an imbalanced immune response to an infection that causes over 10 million deaths annually, particularly in low and middle-income countries. Current clinical management of sepsis relies on infection control, homeostasis restoration, and systemic corticosteroid therapy. Unfortunately, while beneficial, corticosteroid regimens, including dexamethasone, can lead to adverse effects such as neurological and metabolic complications, limiting their use. In this work, we decided to develop a scalable production method using only approved and cost-effective materials. We also conceived our formulation to be freeze-drying friendly to allow its use within various healthcare systems. Following those concepts, we designed DSPE-PEG(2000)-based micelles to encapsulate dexamethasone, and improve its in vivo efficacy by extending blood circulation time and targeting innate blood immune cells. First, the physicochemical properties, stability, in vitro release kinetics, and efficacy of dexamethasone-loaded micelles were comprehensively measured to demonstrate the platform's robustness. The therapeutic in vivo efficacy of dexamethasone-loaded micelles and their ability to increase animal survival was exhibited in two murine sepsis models, an endotoxemia model, and the cecal ligation and puncture model. Various biodistribution and ex vivo fluorescence imaging assays revealed that using micelles led to an improved blood circulation time and a preferential accumulation within immune cells that could explain the enhanced efficacy of dexamethasone-loaded micelles compared to the soluble form of the drug used clinically. Altogether, our results indicate that this robust micellar delivery system can potentially improve the anti-inflammatory therapy of dexamethasone, offering a safer and more effective alternative to conventional corticosteroid regimens in sepsis.

Critically ill patients suffering from sepsis are at an increased risk of morbidity and mortality due to its serious complications. Saffron as an herbal medicine has been proven to have anti-inflammatory and anti-oxidative stress effects previously. Hence, this study aimed to determine how saffron supplementation affected inflammatory and hematological factors in patients admitted to the intensive care unit (ICU) with sepsis.

In this double-blind clinical trial, 90 ICU sepsis patients with GCS lower than 13 were randomized to receive either an intervention tablet containing 100 mg of saffron or a placebo tablet containing 100 mg of corn starch for seven days. Before and after the intervention, clinical, inflammatory, hematological, and mortality parameters were assessed.

After seven days, the saffron group showed a significantly decline from baseline compared to the placebo group in inflammatory markers, including CRP (-24.58 ± 22.16 vs. -2.42 ± 30.86; P < 0.001), ESR (-5.36 ± 28.75 vs. 24.29 ± 28.24; P < 0.001), IL-6 (-22.09 ± 25.22 vs. -4.02 ± 20.04; P < 0.001), IL-18 (-9.56 ± 9.31 vs. -0.89 ± 3.38; P < 0.001), and TNF-α (-2.52 ± 3.79 vs. -0.035 ± 2.35; P < 0.001). Regarding clinical outcomes, significant improvements were observed in APACHE II (-2.55 ± 5.47 vs. 0.78 ± 3.37; P = 0.003), SOFA (-1 ± 1.07 vs. -0.05 ± 1.53; P < 0.001), NUTRIC score (-1.2 ± 1.01 vs. 0.2 ± 0.87; P < 0.001), and WBC count (-4176.34 ± 4063.01 vs. 61.57 ± 4118.97; P < 0.001). Moreover, the effect sizes (Cohen's d) for these factors ranged from moderate to large, except for IL-6, which had a small effect size (d = -0.38). However, no significant differences were found between the groups in the Glasgow Coma Scale, FOUR Score, 28-day and 90-day mortality rates, or other hematological parameters (P > 0.05).

Saffron administration in sepsis patients admitted to the ICU led to significant improvements in inflammatory markers and some clinical parameters. However, the clinical significance of these findings remains to be fully established.

Iranian Registry of Clinical Trials: IRCT20201129049534N8. It was registered on 17 March 2024.

Existing guidelines emphasize the importance of initial fluid resuscitation therapy in sepsis management. However, in previous meta-analyses, there have been inconsistencies in differentiating between spontaneously breathing and mechanically ventilated septic patients.

To consolidate the literature on the predictive accuracy of changes in the inferior vena cava diameter (∆IVC) for fluid responsiveness in septic patients.

The Embase, Web of Science, Cochrane Library, MEDLINE, PubMed, Wanfang, China National Knowledge Infrastructure (CNKI), Chinese Biomedical (CBM) and VIP (Weipu) databases were comprehensively searched. Statistical analyses were performed with Stata 15.0 software and Meta-DiSc 1.4.

Twenty-one research studies were deemed suitable for inclusion. The sensitivity and specificity of ∆ IVC were 0.84 (95% CI 0.76, 0.90) and 0.87 (95% CI 0.80, 0.91), respectively. With respect to the distensibility of the inferior vena cava (dIVC), the sensitivity was 0.79 (95% CI 0.68, 0.86), and the specificity was 0.82 (95% CI 0.73, 0.89). For collapsibility of the inferior vena cava (cIVC), the sensitivity and specificity values were 0.92 (95% CI 0.83, 0.96) and 0.93 (95% CI 0.86, 0.97), respectively.

The results indicated that ∆IVC is as a dependable marker for fluid responsiveness in sepsis patients. dIVC and cIVC also exhibited high levels of accuracy in predicting fluid responsiveness in septic patients.

The triglyceride‒glucose body mass index (TyG-BMI) has been recognized as a significant predictor of cardiovascular disease risk and plays a crucial role in assessing insulin resistance. However, the correlation between the TyG-BMI and clinical outcomes in patients with sepsis and acute heart failure (AHF) has not been sufficiently explored. This study aimed to investigate the associations between TyG-BMI and clinical outcomes in patients with sepsis and AHF.

We conducted a retrospective analysis of ICU-admitted patients via data from the MIMIC-IV database. Multivariable logistic regression, sensitivity analysis, and restricted cubic spline (RCS) models were used to assess the relationship between TyG-BMI and all-cause mortality. K‒M survival analysis and Boruta analysis were employed to evaluate the predictive value of the TyG-BMI. Subgroup analyses considered the effects of age, sex, ethnicity, and comorbidities.

Among the 1,729 patients, a higher TyG-BMI was associated with lower all-cause mortality at 90 and 180 days. Each standard deviation increase in the TyG-BMI was linked to 0.2% and 0.3% reductions in 90-day and 180-day all-cause mortality, respectively. Kaplan‒Meier analysis revealed significantly lower all-cause mortality in patients with higher TyG-BMIs (P < 0.0001). The RCS model revealed a nonlinear relationship between the TyG-BMI and mortality. Boruta analysis identified the TyG-BMI as an important clinical feature. Sensitivity analyses revealed that the association remained significant after patients with myocardial infarction, malignancies, or missing data were excluded. The subgroup analysis revealed that for the 90-day and 180-day mortality rates, significant interactions were found only in the subgroup of patients with kidney diseases (P < 0.05).

The TyG-BMI may have potential value in predicting mortality in ICU patients with sepsis and AHF, supporting early risk assessment and clinical intervention. This study provides critical insights into patient prognosis.

The plasma histidine-rich glycoprotein concentration is a marker of sepsis severity. In this study, we generated selective and specific monoclonal antibodies against histidine-rich glycoprotein for use in a prototype enzyme-linked immunosorbent assay-based in vitro diagnostic system. First, we investigated the properties of monoclonal antibodies produced by 21 hybridomas that we developed using immunized mice, and we identified monoclonal antibodies 69-1A and 75-2D to be the most suitable combination for use in the sandwich enzyme-linked immunosorbent assay. Wild-type histidine-rich glycoprotein (Form-1, 75 kDa) with a proline residue at amino acid position 204 is the most common isoform of the protein in humans, followed by its variant (Form-2, 77 kDa), which has a serine residue at position 204. The epitope mapping was examined for the HRG amino acid sequence with 69-1A and 75-2D mAbs to achieve the identification of respective specific binding domains, though the other kinds of mAbs showed considerably complex domains. The identified epitopes recognized by 69-1A and 75-2D monoclonal antibodies did not span position 204. Furthermore, immunoprecipitation-immunoblotting analysis showed that the 69-1A and 75-2D monoclonal antibodies could bind to both Form-1 and Form-2 in human plasma samples. Thus, these two new antibodies can be used to clearly detect both forms of histidine-rich glycoproteins in human plasma samples. In our analysis of clinical samples by enzyme-linked immunosorbent assays using various combinations of our newly synthesized antibodies, we found that the histidine-rich glycoprotein concentration was significantly lower in plasma samples from septic patients than in those from healthy volunteers (p < 0.01). Thus, our novel analysis system using the new antibodies is expected to be a useful tool for sepsis research, and it may be adapted as an in vitro diagnostic tool for many other kinds of diseases in the future.

Sepsis represents a high-risk mortality cohort among patients with severe community-acquired pneumonia (SCAP). Rapid and precise identification along with prompt decision-making, serves as a practical approach to improve patient prognosis.

This retrospective observational study enrolled adult patients with severe community-acquired pneumonia (SCAP) who were continuously hospitalized in the intensive care unit (ICU) of West China Hospital, Sichuan University, from September 2011 to September 2019. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors for co-sepsis, followed by the utilization of LASSO regression to filter features to establish a nomogram. Model robustness was evaluated via the C index, receiver operating characteristic (ROC) analysis, and calculation of the area under the curve (AUC). Furthermore, its predictive accuracy was assessed via decision curve analysis (DCA).

In total, 5855 SCAP patients were included in the present study, of whom 654 developed sepsis. Patients with sepsis exhibited a prolonged length of stay in the ICU and higher mortality rates, indicating a worse prognosis than those without sepsis. We identified 15 independent risk factors associated with the development of sepsis in SCAP patients. Further analysis incorporating 9 of these features to construct a nomogram demonstrated a C index of 0.722 (95%CI 0.702-0.742), including lactate, D-dimer, respiratory rate, heart rate, albumin, hemoglobin, activated partial thromboplastin time (APTT), glucose, and C-reactive protein (CRP) levels. The AUC values and DCA curves demonstrated that the model exhibited superior accuracy and overall net benefit in predicting co-sepsis development compared with the qSOFA, CURB-65, SOFA, and APACHE II scores. Additionally, the calibration curve confirmed good concordance between the predicted probabilities of the model.

This study investigated the risk factors for co-sepsis in SCAP patients and constructed an expedited, cost-effective and personalized model for predicting the probability of co-sepsis.

Research studies have examined saffron's effects on inflammation, infection, and oxidative stress. Nevertheless, the effects of saffron on sepsis patients in the intensive care units (ICUs) have not yet been studied. Hence, this study will examine the effects of saffron supplementation on oxidative stress biomarkers, inflammation factors, and clinical outcomes in critically ill septic patients.

Ninety patients with sepsis will participate in this parallel double-blind, randomized clinical controlled trial. In addition to usual care, the intervention group (n=45) will receive a daily tablet containing 100 mg/day saffron for 7 days, and the control group (n=45) will receive a placebo tablet containing 100 mg/day corn starch for the same duration. Acute Physiology and Chronic Health Evaluation II (APACHE II), the Sequential Organ Failure Assessment (SOFA), and the NUTRIC Score will be used to assess the patients' clinical and nutritional status at the beginning and end of the study. Inflammatory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and IL-18, indicators of oxidative stress including malondialdehyde (MDA), glutathione peroxidase (GPx), catalase, superoxide dismutases (SODs), and total antioxidant capacity (TAC), level of Glasgow Coma Scale (GCS), complete blood count (CBC), and lactate dehydrogenase (LDH) will be evaluated at beginning and end of the study. Twenty-eight days after the start of the intervention mortality rates will be assessed.

Due to the anti-inflammatory, antioxidant, and antimicrobial effects, saffron might have beneficial effects in critically ill patients with sepsis.

Background: The relationship between the partial pressure of oxygen in arterial blood (PaO 2 ) and the prognosis of sepsis patients, and its potential variation over time, remains unclear. The optimal PaO 2 range for sepsis patients has always been a contentious issue, with no consensus. We aimed to explore the association between different levels of PaO 2 exposure over time and the 28-day mortality of sepsis patients, and to identify the optimal PaO 2 range for sepsis patients within a specific time frame. Methods: We retrieved data on adult patients diagnosed with sepsis within 24 h before or after intensive care unit (ICU) admission from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.2) database. We excluded patients who were not admitted to the ICU for the first time, those with ICU stay <24 h, and those without PaO 2 results during their ICU stay. We calculated the time-weighted average (TWA) of PaO 2 and used piece-wise exponential additive mixed models (PAMMs) to estimate the time-dependent changes in the association between TWA-PaO 2 and patient prognosis. Results: A total of 16,880 sepsis patients were included in the MIMIC cohort. Results indicated that patients' TWA-PaO 2 correlates with increased 28-day mortality after ICU admission in sepsis patients, and this association was mainly manifested in the early course of the disease. With a time window of the first 1-7 days after ICU admission, the optimal TWA-PaO 2 range for sepsis patients was ≥130 mmHg and ≤160 mmHg. Increased exposure time, proportion of exposure time, and exposure dose of high-risk PaO 2 outside the range were all associated with an increased risk of 28-day mortality. Conclusion: PaO 2 in sepsis patients should be closely monitored. During the first 1-7 days of ICU admission, PaO 2 should be maintained within the range of ≥130 mmHg and ≤160 mmHg. A dose-dependent relationship exists between high-risk PaO 2 outside the range and patient outcome.

Background: Proteolyse is one of the causes of loss of lean body mass, and depend of insulin. Proteintyrosine phosphatase 1B (PTP1B) and intestinal permeability (evaluated by zonulin) contribute of insulin metabolism. The objectives were to explore the relationship between PTP1B, zonulin level and body composition during septic shock in humans. Material and Methods: This is a prospective study including patients admitted to intensive care unit for septic shock. Blood samples were collected on days 1 (D1) and 4 (D4) for study expression of PTPT1b (PCR) and zonulin. Muscle mass was evaluated by fat-free mass (by Bioelectrical impedance analysis) and rectum femoris cross-sectional area by ultrasound. Results: We included 52 patients with a mean IGSII 53 (39-65), and a mortality in intensive care unit of 32%. Between D1 and D4, area of right quadriceps muscle and average of quadriceps muscles decreased ( P = 0.002 and 0.009, respectively). We observed no modification in fat-free mass. Median of PTP1b at D1 was 5.03 (2.36-10.96). Median of plasmatic zonulin at D1 was 156.6 ng/mL (56.3-277.9). We did not find any correlation between PTP1b, zonulin expression, and muscle composition. The mortality rate was more important in patients with a low average quadriceps thickness (QT) or quadriceps area (QA) ( P < 0.01), and tendency for patients who had an elevated zonulin in admission. By contrast, we did not observe significant associations between fat-free mass and PTP1B and mortality at D28. Conclusion: We observed a trend of correlation between the whole blood PTPN1 gene expression at D1 and D4/D1 thickness of left quadriceps muscle, because this is the only data which has a potential to address the relationship body mass change and proteolysis.

Sepsis is a leading cause of death in intensive care units (ICU). Sepsis survivors are often left with significant morbidity, termed post-intensive care syndrome (PICS), impacting post-sepsis life. The aim was to present detailed data on the prognostic and functional long-term outcomes of ICU patients with sepsis in Japan, which is currently lacking and therefore prevents development of targeted solutions.

A multicenter prospective study, involving 21 ICUs in 20 tertiary hospitals in Japan, included all consecutive adult ICU patients between November 2020 and April 2022, and diagnosed with sepsis at ICU admission (Sepsis 3). Follow-ups were performed at 3, 6, and 12 months after hospital discharge by telephone and mail. Primary outcome was death or incidence of PICS, defined by any of physical dysfunction (Barthel Index ≤ 90), cognitive dysfunction (Short Memory Questionnaire < 40), or mental disorder (any subscales for anxiety or depression of Hospital Anxiety and Depression Scale ≥ 8, or Impact of Event Scale-Revised ≥ 25). Secondary outcomes included Quality of Life (QOL), employment, and use of hospital, emergency, rehabilitation, and psychiatric services. A multivariable analysis investigated independent factors associated with each dysfunction at each follow-up.

A total of 339 patients were included (median age 74 [67-82] years, 60% male, 77% septic shock, and a median SOFA of 9 [6-12]). Mortality was 23% at hospital discharge, increasing to 37% at 12 months. The rate of death for those who met PICS Criteria at hospital discharge was 89%, with a death or PICS incidence of 73%, 64%, and 65% at 3, 6, and 12 months, respectively. Limited improvements in QOL and return to work (44%), high rates of hospital readmissions (40%), frequent emergency service usage (31%), and low utilization of rehabilitation and psychiatric services (15% and 7%) were identified over the first year. The incidence of any PICS-related dysfunction was consistently an independent factor for the incidence of the same dysfunction at the following follow-ups.

This multicenter study identified the distinct realities of post-sepsis life in Japanese ICU patients, highlighting the unique challenges in improving their functions and returning to daily life. Trial Registration University Hospital Medical Information Network UMIN000041433.

Sepsis is a leading cause of morbidity and mortality in children, requiring early recognition for timely intervention. Traditional biomarkers like C-reactive protein (CRP) are widely used but have limitations in specificity and early detection. Procalcitonin (PCT) has emerged as a promising alternative for differentiating bacterial infections from viral illnesses. This study aims to evaluate the diagnostic performance of PCT and CRP in identifying sepsis among febrile pediatric patients presenting to the emergency department (ED).

We conducted a retrospective, observational study at a tertiary hospital from January 2022 to January 2024. A total of 208 children aged 1 month to 14 years with fever (≥ 38 °C) were included. Patients were categorized into sepsis (n = 84) and non-sepsis (n = 124) groups based on clinical assessment and blood culture results. Biomarker levels, patient demographics, clinical outcomes, and disposition were analyzed.

Elevated PCT and CRP levels were significantly associated with sepsis. PCT demonstrated earlier elevation compared to CRP, correlating with higher rates of PICU admission (34.7% vs. 11.1%, p < 0.001). Blood culture positivity was a strong predictor of severe sepsis (OR: 9.369, p < 0.0003). Logistic regression identified high-grade fever, chronic disease, and viral co-infections as additional risk factors.

PCT is a superior early biomarker for detecting invasive bacterial infections compared to CRP. Incorporating PCT in sepsis protocols can improve early diagnosis, guiding prompt and appropriate management in pediatric ED settings.

Splenectomy is required for many haematological conditions and causes an increased risk of severe infections and vascular events. The association between underlying haematological disease, age at splenectomy and post-splenectomy complications was explored among 1348 splenectomized patients, followed with a median follow-up time of 13 years and affected by transfusion-dependent thalassaemia, non-transfusion-dependent thalassaemia (NTDT), sickle cell anaemia (SCA), congenital haemolytic anaemias, autoimmune haematological disorders and trauma. Our main statistical approach was based on interaction analyses within competing-risk survival models. The baseline risk profile differed across diagnostic categories, with SCA being particularly susceptible to infectious complications and NTDT and SCA to vascular events (p < 0.001). The age at splenectomy did not impact on infectious risk but rather older age at splenectomy was associated with increased risk for vascular complications. Furthermore, the risk of developing a post-splenectomy complication was persistent throughout the observation period and not limited to the first 2-3 years after splenectomy. The probability of a post-splenectomy complication was highly dependent on the underlying disease and not on the age at splenectomy, so the indications for splenectomy must be based on careful assessment of pros and cons in the individual disease, with no need to delay surgery after a certain age when clinically indicated.

Septic shock is one of the most lethal conditions in ICU, and early risk prediction may help reduce mortality. We developed a TOPSIS-based Classification Fusion (TCF) model to predict mortality risk in septic shock patients using data from 4872 ICU patients from February 2003 to November 2023 across three hospitals. The model integrates seven machine learning models via the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS), achieving AUCs of 0.733 in internal validation, 0.808 in the pediatric ICU, 0.662 in the respiratory ICU, with external validation AUCs of 0.784 and 0.786, respectively. It demonstrated high stability and accuracy in cross-specialty and multi-center validation. This interpretable model provides clinicians with a reliable early-warning tool for septic shock mortality risk, facilitating early intervention to reduce mortality.

Sepsis often codevelops with brain damage, and the mechanisms underlying sepsis-related brain damage have been elucidated. However, only a few studies have reported the diagnostic imaging assessments for brain damage in sepsis. Therefore, in this study, we analyzed the brain magnetic resonance (MR) imaging (MRI) findings of patients with sepsis.

This single-center prospective observational study included 71 patients with sepsis who underwent brain MRI, regardless of the presence or absence of shocks and acute neurological abnormalities. The MR images were classified according to the presence or absence of acute cerebral ischemia and leukoencephalopathy, with normal findings indicating neither condition.

The MR images of 18 patients (25.3%) showed acute cerebral ischemia and leukoencephalopathy. Furthermore, 44 patients (62.0%) had only leukoencephalopathy. In terms of patient demographic characteristics and neurological outcomes, significant differences were noted among patients with acute cerebral ischemia findings, those with leukoencephalopathy findings, and those with neither. There were significant differences in age (P = 0.0296), neurological findings (P = 0.0057), number of days in the intensive care unit (P = 0.0239), acute disseminated intravascular coagulation score during hospitalization (P = 0.0363), and the Katz index at discharge or transfer (P = 0.0020) among these groups.

Among patients with sepsis, 25.3% showed acute cerebral ischemia findings on brain MRI, regardless of illness severity, including hypoxia and hypotension, and presence of shock. Abnormal MRI findings were also observed in patients without acute brain dysfunction. Importantly, abnormal brain MRI findings were associated with worse neurological outcomes.

To investigate the clinical effects of ultrasound-guided precise nasojejunal catheterization in critically ill patients receiving enteral nutrition.

A total of 120 patients were randomly divided into control and experimental groups in a 1:1 ratio. The control group underwent blind transnasal jejunal catheterization, and the experimental group underwent ultrasound-guided transnasal jejunal catheterization. Indices related to catheterization, complications of catheterization, and nutritional status before and after catheterization were used as observation indices.

The average catheterization time of the experimental group was shorter (21.28 ± 8.96 min), the success rate of one-time catheterization was significantly greater than that in the control group (93.3% vs. 80.0%), and the probability of catheter displacement/detachment was significantly lower in the experimental group than in the control group (p < 0.05). Prealbumin level, total serum protein level, and absolute number of lymphocytes were significantly greater than those in the control group and before catheterization (p < 0.05).

In enteral nutrition intervention for critical patients, accurate ultrasound-guided nasojejunal tube placement has the advantages of short operation time, high success rate, safety, and good nutritional support and is expected to be an ideal method for successful nasojejunal tube placement.

Background: Sepsis-associated acute kidney injury (AKI) is linked to increased mortality and prolonged hospital stays. The exact relationship between central venous pressure (CVP) and AKI remains unclear. We explored the correlation between CVP and AKI in septic shock patients. Methods: This retrospective study included adult patients with septic shock admitted to Mayo Clinic Rochester between 2006 and 2018. CVP levels were measured at 6, 12, 24, and 48 h after the diagnosis of sepsis, and patients were stratified into two groups based on CVP levels (CVP < 8 or ≥8 mmHg). Results: Of 5600 patients with septic shock, 3128 patients without AKI on admission are included. One-thousand-and-ninety-eight patients (35.1%) developed AKI within a median of 4.4 days. The median CVP levels and frequency of elevated CVP at 6, 12, 24, and 48 h are significantly higher in the AKI group. Elevated CVP (≥8 mmHg) at 6, 12, 24, and 48 h is associated with AKI incidence, even after adjusting for mean arterial pressure (MAP) levels. This association, after multivariable adjustments, only remains significant at 12 h with an odds ratio (OR) of 1.60 (95% CI, 1.26-2.05), p < 0.001 and 48 h with an OR of 1.60 (95% CI, 1.29-1.99), p < 0.001. Conclusions: Our findings indicate that CVP ≥ 8 mmHg is strongly associated with an increased risk of AKI, even after adjusting for MAP at the 12 and 48 h time points. These findings underscore a critical 12 or 48h window for interventions to lower CVP.

The dysregulated stress response is a key pathological mechanism underlying sepsis and is strongly associated with poor clinical outcomes. Stress hyperglycemia, a common manifestation of this response, may provide valuable prognostic information in sepsis patients. The stress hyperglycemia ratio (SHR) offers a more accurate reflection of the stress response and may be instrumental in assessing sepsis prognosis.

This study aimed to investigate the relationship between SHRs and clinical outcomes in sepsis patients. Data were obtained from the Medical Information Mart for Intensive Care IV database. Demographic information, intensive care unit (ICU) parameters within the first 24 h, laboratory results, insulin administration, survival time, and outcomes were extracted for analysis. Four SHR metrics (SHRfirst, SHRmin, SHRmax, and SHRmean) were calculated based on blood glucose values during the first 24 h of ICU admission (first, minimum, maximum, and mean, respectively). The predictive performance of each SHR metric was compared using the area under the receiver operating characteristic (ROC) curve. Kaplan-Meier survival analysis was performed to assess survival rates across groups defined by ROC curve-generated cut-off values. Associations between SHR and 28-day as well as 1-year mortality were further examined using both univariate and multivariate Cox regression analyses.

A total of 5,025 sepsis patients were included, of whom 656 died within 28 days of ICU admission. SHR was significantly higher in the non-survivor group. Among the SHR metrics, SHRmax demonstrated the highest predictive value for both 28-day and 1-year mortality. Higher SHR values were consistently associated with increased mortality (all P < 0.001). For SHRmax, each 1-unit increase was associated with a 77% increase in mortality in univariate analysis and a 71.6% increase in multivariate analysis. Sensitivity analyses indicated that the relationship between SHR and mortality was stronger in patients without diabetes.

SHR serves as a robust marker of the dysregulated stress response in sepsis and holds significant prognostic value, particularly SHRmax, in predicting mortality. These findings underscore the potential clinical utility of SHR in guiding therapeutic strategies aimed at modulating the stress response and blood glucose levels in critically ill sepsis patients. Further research is warranted to explore SHR-targeted interventions in sepsis management.

To compare the efficacy of continuous renal replacement therapy (CRRT) using either oXiris or conventional hemopurification filters in the treatment of intra-abdominal sepsis.

We conducted a retrospective analysis of septic patients with severe intra-abdominal infections admitted to our hospital from October 2019 to August 2023. Patients who meet the criteria for intra-abdominal sepsis based on medical history, symptoms, physical examination, and laboratory/imaging findings were included.

pregnancy, terminal malignancy, prior CRRT before intensive care unit admission, pre-existing liver or renal failure. Heart rate (HR), mean arterial pressure, oxygenation index, lactic acid level (Lac), platelet count (PLT), neutrophil percentage, serum levels of procalcitonin, C-reactive protein, interleukin (IL)-6, norepinephrine dosage, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) scores before and after 24 h and 72 h of treatment, as well as ventilator use time, hemopurification treatment time, intensive care unit and hospital lengths of stay, and 14-day and 28-day mortality were compared between patients receiving CRRT using either oXiris or conventional hemofiltration. Statistical analysis was performed using SPSS Statistics 26.0 software, including the construction of predictive models via logistic regression equations and repeated measures ANOVA.

Baseline values including time to antibiotic administration, time to source control, and time to initiation of CRRT were similar between the 2 groups (all p>0.05). Patients receiving conventional CRRT exhibited significant changes in HR but of none of the other indexes at the 24 h and 72 h time points (p=0.041, p=0.026, respectively). The oXiris group showed significant improvements in HR, Lac, IL-6, and APACHE II score 24 h after treatment (p<0.05); after 72 h, all indexes were improved except PLT (all p<0.05). Intergroup comparison disclosed significant differences in HR, Lac, norepinephrine dose, APACHE II, SOFA, neutrophil percentage, and IL-6 after 24 h of treatment (p<0.05). Mean arterial pressure, serum levels of procalcitonin, C-reactive protein, SOFA score, and norepinephrine dosage were similar between the 2 groups at 24h (p>0.05). Except for HR, oxygenation index, and PLT, post-treatment change rates of △ (%) were significantly greater in the oXiris group (p < 0.05). Duration of ventilator use, CRRT time, and intensive care unit and hospital lengths of stay were similar between the 2 groups (p>0.05). The 14-day mortality rates of the 2 groups were similar (p=0.091). After excluding patients whose CRRT was interrupted, 28-day mortality was significantly lower in the oXiris than in the conventional group (25.0% vs. 54.2%; p=0.050). The 28-day mortality rate increased by 9.6% for each additional hour required for source control and by 21.3% for each 1-point increase in APACHE II score.

In severe abdominal infections, the oXiris filter may have advantages over conventional CRRT, which may provide an alternative to clinical treatment. Meanwhile, early active infection source control may reduce the case mortality rate of patients with severe abdominal infections.

In the Conservative vs. Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care (CLASSIC) trial, restriction of IV fluid volumes led to similar overall mortality in ICU patients with septic shock. We assessed if variation in standard IV fluid treatment intensity across sites impacted the effects of fluid restriction.

Secondary analysis of randomized clinical trial.

ICU.

The CLASSIC trial enrolled adult ICU patients with septic shock. We included 1366 participants from 19 sites, representing 88% of the full trial population. All sites with greater than or equal to 15 participants in the standard-fluid group were included in this study.

Restrictive vs. standard IV fluid therapy.

We used machine learning (eXtreme Gradient Boosting) to predict the IV fluid volumes in the first 24 hours in the standard-fluid group while accounting for participant characteristics that could contribute to treatment variations. We then classified sites into intensity subgroups based on the mean differences between predicted and administered IV fluid volumes in the first 24 hours in the standard-fluid group. We assessed the intervention effects on mortality, serious adverse events and reactions, days alive without life support, and days alive out of hospital at day 90 across these intensity subgroups, using hierarchical Bayesian models with weakly informative priors. Sensitivity analyses evaluated intervention effects separately in each site. In the standard-fluid group, the median absolute difference between administered and predicted IV fluid volumes was -118 mL (interquartile range, -1,341 to 1,731 mL; full range, -5,873 to 11,761 mL). Sites were categorized into five intensity subgroups. The absolute differences in mortality across these subgroups ranged from -2.7% point to 1.4% point. We found similar effects of restrictive vs. standard IV fluid treatment on all outcomes within the intensity subgroups. Results were similar in the sensitivity analyses.

Among adult ICU patients with septic shock, variation in standard IV fluid volumes across sites did not substantially impact the effects of fluid restriction on outcomes after accounting for patient characteristics.

This study investigates the effects of continuous versus intermittent hydrocortisone administration on septic shock patients. Sixty patients were randomized into two groups: one receiving intermittent doses of 50 mg of hydrocortisone every 6 h and the other a continuous infusion of 200 mg/day. After a 7-day treatment period and a 28-day follow-up, we observed no significant differences in the duration of sustained shock, hospital, and ICU stays between the groups. However, those in the continuous infusion group experienced shorter periods of mechanical ventilation and vasopressor use, with significant improvements in hemodynamic stability. Both treatment approaches improved arterial pressure and lactate clearance, with no significant differences in heart rate or cortisol levels between the groups at the end of the treatment. Notably, shock reversal rates were higher and 28-day mortality rates were lower in the continuous infusion group. These results suggest that continuous hydrocortisone infusion may be more effective for managing septic shock, potentially leading to better patient outcomes without an increase in adverse reactions. This method could be considered for broader clinical implementation in septic shock treatment strategies.

This study investigated active Epstein-Barr virus (EBV) infection in children and examined the associations among EBV deoxyribonucleic acid (DNA) load, infection types, disease severity, and immune characteristics.

A total of 35,956 pediatric patients who underwent EBV DNA load testing were included. Patients were categorized based on their EBV DNA levels and infection status.

Spearman's rank correlation analysis revealed a positive association between EBV DNA levels and the mortality rate, as well as the incidence rates of acute kidney injury (AKI), respiratory failure, cardiovascular complications, coagulation abnormalities, and liver injury. Mortality risk significantly increased when EBV DNA exceeded 1 × 105 copies/mL (adjusted odds ratio: 10.53, 95% confidence interval: 2.38-46.59, P < 0.05). As EBV DNA levels increase, the rise in mortality rate during activation- immunoglobulin G (IgG+) was more pronounced than that observed during primary infections. Gaussian mixture model clustering identified two immune clusters. Cluster 0 exhibited elevated pro-inflammatory indicators (IFN-γ, IL-6) and anti-inflammatory indicator (IL-10) levels, along with reduced immune cell counts. This cluster showed higher activation-IgG+ and mortality rates compared with Cluster 1.

An elevated EBV DNA load (> 1 × 105 copies/mL) in children is associated with increased mortality risk. High pro-inflammatory and anti-inflammatory states, coupled with low immune cell numbers, indicate critical condition. Simultaneous examinations of EBV DNA, antibodies, and immune status are recommended, especially for children with EBV DNA > 1 × 105 copies/mL, emphasizing the need for caution in those with activation-IgG+ and immune dysregulation.

There is insufficient evidence regarding the use of second-line vasopressors following norepinephrine administration in the post-resuscitation management of patients with out-of-hospital cardiac arrest (OHCA). Therefore, this study aimed to investigate the survival outcomes between norepinephrine plus epinephrine and norepinephrine plus vasopressin as vasopressor combinations after return of spontaneous circulation (ROSC) in patients with OHCA. This retrospective observational study included data from a prospective multicenter registry. Adult patients with OHCA who achieved sustained ROSC and received vasopressor combinations of norepinephrine plus epinephrine or norepinephrine plus vasopressin were included in the study. The variable of interest was the vasopressor combination either norepinephrine plus epinephrine or norepinephrine plus vasopressin within 24 h from sustained ROSC. The primary outcome was survival to discharge. Multivariable logistic regression analysis was conducted. Between October 2015 and June 2024, 901 patients were analyzed. Survival to discharge and good neurological outcome were significantly higher in the group with norepinephrine plus epinephrine than in the group with norepinephrine plus vasopressin (17.0% vs. 9.1%, p = 0.001, and 8.1% vs. 3.2%, p = 0.002, respectively). Norepinephrine plus vasopressin was independently associated with worse survival to discharge and neurological outcome compared to norepinephrine plus epinephrine, after adjusting for potential confounders (adjusted odds ratio [aOR] 0.454, 95% confidence interval [CI] 0.277-0.746, p = 0.002 and aOR 0.346, 95% CI 0.150-0.794, p = 0.012, respectively). These findings were maintained in multiple regression models and sensitivity analyses. Norepinephrine plus epinephrine administration within 24 h from sustained ROSC showed better survival to discharge than norepinephrine plus vasopressin in patients with OHCA.

Combination therapy with a beta-lactam and an aminoglycoside is currently recommended for the empirical treatment of urosepsis. Nephrotoxicity is the most common adverse effect of aminoglycosides and acute kidney injury (AKI) has a significant prognostic impact in septic shock. This study aimed to evaluate the impact of empirical antibiotic therapy with or without an aminoglycoside on survival and renal outcomes in patients admitted to the intensive care unit (ICU) with urosepsis.

This multicenter, retrospective, comparative study included all adults admitted to the ICU for urinary sepsis or septic shock between January 2015 and May 2022 in four ICUs of three university hospitals within the Assistance Publique-Hôpitaux de Paris (APHP). The primary outcome was mortality on day 30 after ICU admission. Secondary endpoints included the lack of renal recovery, the need for new renal replacement therapy (RRT), the Major Adverse Kidney Events at day 30 (MAKE 30) and ICU length of stay. Confounding by indication was taken into account using propensity score weighting.

A total of 580 patients were included, median age was 69 years (interquartile: 58-77) and 53.6% were male. Overall, 335 patients (57.8%) were in septic shock and 448 (79.2%) had AKI on admission. A total of 579 patients (99.8%) received a beta-lactam as empirical therapy (with (n = 444) or without (n = 136) aminoglycosides). The overall 30-day mortality rate was 10.5% (61/580). After propensity score weighting, the mortality rate in patients receiving aminoglycosides was 7.7% (7/91) compared to 12.1% (11/91) in those not receiving aminoglycosides (adjusted hazard ratio (aHR) = 0.65 [0.35; 1.23], p = 0.19). No significant differences were found in the lack of renal recovery at day 30 (aHR = 0.88 [0.49; 1.58], p = 0.67), the need for new RRT within 30 days (aHR = 1.01 [0.54; 1.88], p = 0.97), MAKE 30 (aHR = 0.94 [0.60; 1.50], p = 0.81), and ICU length of stay among survivors (aHR = 1.07 [0.87; 1.31], p = 0.53).

Including aminoglycosides in the empirical antibiotic therapy did not significantly improve 30-day survival in patients admitted to the ICU for urosepsis. However, the use of aminoglycosides was not associated with worse renal outcomes.

Oral medication is preferred for its convenience; however, efficient drug delivery remains challenging due to issues such as poor solubility, and absorption caused by mucosal barriers, which result in low bioavailability. In this review, we discuss new strategies integrating robotic capabilities into oral formulations to enhance drug delivery. Such robotic pill systems leverage the efficient propulsion of biological and synthetic micromotors to accelerate pill disintegration and overcome mucosal barriers, increasing bioavailability with lower doses and fewer side effects. In addition, advanced bioinspired robotic capsules, including microneedles, microinjectors, and microjet systems, offer enhanced macromolecule bioavailability comparable with that achieved with subcutaneous injections. The future of precision medicine lies in encapsulating diverse micromotors (with unique capabilities) within pharmaceutical carriers, offering groundbreaking opportunities for enhanced therapeutic interventions.

Bacteremia is a potential systemic complication of bronchopneumonia (BP) in dairy calves, which increases the risk of sepsis and mortality. However, data on bacteremia in farm conditions is still limited. This study investigates the prevalence of bacteremia in calves with BP on farms, examining isolated pathogens and the associations between thoracic ultrasonography (TUS) and non-endoscopic bronchoalveolar lavage (nBAL) findings.

The study enclosed 13 dairy farms and included 211 eligible preweaned dairy calves, of which 88 were diagnosed with BP based on a highly sensitive threshold of ≥ 1 cm for lung consolidation detected by TUS. The affected calves underwent non-endoscopic bronchoalveolar lavage (nBAL) and blood culture procedures. Blood culture results showed a positivity rate of 6.8%, identifying Salmonella Dublin in five cases and Campylobacter fetus in one case. Twenty-four (27.2%) blood samples grew presumed bacterial contaminants, while 58 (65.9%) samples had no growth. In contrast, nBAL samples revealed a 75% positivity rate, with Pasteurella multocida and Mycoplasma bovis being the most frequently identified pathogens. No associations were observed between TUS-detected lung lesions and bacteremia. Notably, BP pathogens were not identified in blood cultures, except for one instance where Salmonella Dublin was detected in the nBAL and blood culture.

The study indicates a low prevalence of bacteremia in dairy calves with BP diagnosed through TUS, suggesting that recommending treatment or revisions in disease management related to potential bacteremia in these patients may not be warranted. The findings imply that lung lesions detected via TUS may occur independently of bacteremia, highlighting the value of TUS for early diagnosing and monitoring BP in field conditions.

Melioidosis is a tropical infectious disease caused by Burkholderia pseudomallei, characterised by a high case fatality rate.

We summarized the cases of melioidosis at Sanya People's Hospital in Hainan over the past eleven years. This information served as a reference for the epidemiological study, diagnosis, treatment, and prevention of melioidosis in China.

A retrospective study was conducted to compile clinical data from 138 melioidosis patients treated at Sanya People's Hospital in Hainan Province between 2012 and 2023. By comparing these data with domestic and international clinical case studies, the study aimed to summarise the epidemiological characteristics, clinical manifestations, and therapeutic regimens of melioidosis in Hainan Island.

This study revealed that 84.1% of melioidosis cases were observed in males (116/138). The predominant age group affected was 40 to 60 years, constituting 58.0% (80/138) of the total cases. Farmers and fishermen represented the primary demographic, accounting for 63.8% (88/138). The peak incidence of melioidosis in Hainan was observed in the wet season (summer and autumn months), representing 79.0% of cases (109/138). The most prevalent comorbidity in melioidosis cases was diabetes mellitus (77.5%). Bacteremic melioidosis was the predominant infection type (81.9%). Compared with the non-bacteremic group, the bacteremic group exhibited significantly higher incidences of complications, disseminated infections, and abnormal chest CT findings (p < 0.001, respectively). Further analysis indicated that patients with melioidosis and abnormal chest CT findings had an increased likelihood of concurrent bacteremia (OR = 7.289, 95%CI 1.608-33.039, p = 0.010). During the acute phase of anti-infective treatment, 37.7% (52/138) of the patients underwent intravenous anti-infective drug therapy for at least 2 weeks. Additionally, 56.5% (78/138) of the patients received carbapenems (Meropenem or Imipenem, MEPN or IPM) as part of their anti-infective therapy. In the eradication phase of treatment, 66.0% (66/100) of the patients completed the recommended treatment duration of at least 12 weeks. Furthermore, the majority (90/100, 90.0%) received monotherapy with trimethoprim-sulfamethoxazole (TMP-SMX).

In Hainan Island, the prevalence of melioidosis is notably high among middle-aged male outdoor workers, exhibiting a distinct seasonal pattern with most cases occurring during the summer and autumn months. Bacteremia represents the most common form of melioidosis infection, and abnormal chest CT findings in melioidosis patients serve as a significant hint of bacteremia. Currently, the selection of antimicrobial agents for melioidosis treatment in Hainan Province generally adheres to international guidelines; however, the process requires further standardisation.