Critically ill patients are at risk of bleeding from stress ulcers. Comprehensive information regarding United Kingdom stress ulcer prophylaxis (SUP) practices are not available and may change over time. We aimed to describe SUP practices in 2020 and reevaluate the position in 2024.

Critical care pharmacists provided observed SUP practice data for UK adult critical care units via an electronic repository in 2020 and 2024. One response was accepted from each critical care unit at each time point. Data collected included trigger criteria for commencing SUP, primary medication class used, primary SUP cessation criteria, and level of nutritional intake (if part of cessation criteria).

There were high response rates of 70.3% (2020) and 66.7% (2024) of registered UK adult critical care units. Few differences in primary SUP trigger criteria between 2020 and 2024 were seen, with small differences in the categories of 'SUP not used' (p = 0.002) and 'Shock' (p = 0.027) driving statistical significance (χ2(7, 454) = 16.76, p = 0.019). There was a significant change in the primary medication class used for SUP (H2 receptor antagonist 49.4% 2020, vs 0.4% 2024, proton pump inhibitor 44.7% 2020 vs 97.8% 2024; χ2(2, 458) = 159.62, p < 0.001). Primary SUP cessation criteria was 'Patient fed' (66.8% 2020, 64.6% 2024), with most describing this threshold as met when the patient receives full enteral feed (72.0% 2020, 78.8% 2024).

The UK has moved towards proton pump inhibitors as the primary SUP medication class. SUP is most frequently discontinued on establishment of enteral nutrition.

This multicenter randomized controlled trial evaluates the efficacy of thymosin alpha 1 (Tα1) supplementation in preventing organ dysfunction following acute type A aortic dissection (ATAAD) repair. Over 330 patients will be equally assigned to receive either Tα1 plus standard care or placebo with standard management. The primary endpoint involves calculating the difference in mean postoperative Sequential Organ Failure Assessment (SOFA) scores between groups, measured daily from postoperative days 7. By targeting post-operative immune system imbalance, this study aims to establish a novel therapeutic approach for reducing systemic inflammatory response syndrome (SIRS)-mediated organ injury and improving long-term outcomes in this high-risk population. Results will be disseminated through peer-reviewed publications and international conferences.Trial registration: ClinicalTrials.gov Registry (NCT05339529).

Background: Adjunctive vasopressors are added to norepinephrine in one-third of adults with septic shock in the United States. However, effectiveness of this approach is unclear, and treatment recommendations are based on indirect evidence. We sought to synthesize the direct evidence for adjunctive vasopressor administration in adults with septic shock. Methods: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to June 7, 2023. We included randomized clinical trials of adults with septic shock comparing adjunctive treatment with a vasopressin analogue, angiotensin II, methylene blue, hydroxocobalamin, or catecholamine analog to standard care vasopressors. The primary outcome was short-term mortality (at or before 28-30 days or intensive care discharge). Secondary outcomes included kidney replacement therapy, digital/peripheral ischemia, and venous thromboembolism. Random-effects meta-analyses were conducted to derive risk ratios (RRs) and 95% CIs. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. Results: Of 6,763 records, 17 trials (3,813 participants) were included. Compared with standard care, adjunctive vasopressor administration may reduce short-term mortality risk (RR, 0.92 [95% CI, 0.85-1.00], low certainty, 17 trials [3618 participants]) and likely reduces kidney replacement therapy receipt (RR, 0.92 [95% CI, 0.84-1.01], moderate certainty, eight trials [2,408 participants]). Adjunctive vasopressor treatment may increase risk of digital/peripheral ischemia (RR, 2.44 [95% CI, 1.17-5.10], low certainty, nine trials [2,981 participants]) and venous thromboembolism (RR, 16.48 [95% CI, 0.96-283.17], low certainty, one trial [321 participants]). There was some evidence that the pooled estimate for short-term mortality was different (interaction P = 0.13) for trials adjudicated as low risk of bias (RR, 0.95 [95% CI, 0.87-1.05]) compared with trials adjudicated as some concerns or high risk of bias (RR, 0.82 [95% CI, 0.69-0.97]). The findings were robust to multiple sensitivity and subgroup analyses. Conclusions: In adults with septic shock, adjunctive vasopressors may lower short-term death risk and likely lower kidney replacement therapy risk, but may increase risk of adverse effects. In the United States, adjunctive vasopressor use prevalence in septic shock is disconnected from the low evidence certainty for a favorable mortality-to-risk profile.

This study aimed to describe and evaluate a real-time ultrasound-guided (US-guided) drainage technique for effective and safe drainage of gas-forming renal abscesses (GRA) in an intensive care unit(ICU).

This retrospective study included four patients with GRA who were admitted to the ICU of a tertiary care center between September 2021 and September 2023. The patients were all comorbid with severe systemic infections and required drainage of abscesses for infection control. This study describes in detail the process of rapid and precise US-guided drainage of GRA by an ultrasound interventionist through certain maneuvers and techniques.

Six US-guided drainage procedures were completed in four patients, and seven catheters were placed accurately in the abscesses with a 100% success rate. No intraoperative or postoperative complications such as bleeding and peripheral organ damage were observed, and the median time with catheters was 13 days (8-46 days).

The technique of real-time US-guided drainage of GRA can be performed safely in the ICU without the need to leave the ICU, greatly reducing risk.

The adrenocorticotropic hormone (ACTH) test diagnoses relative adrenal insufficiency (RAI) or critical illness-related corticosteroid insufficiency (CIRCI). Initially, guidelines recommended corticosteroid/glucocorticoid (GC) therapy for septic patients with RAI, but later trials did not show a survival benefit, leading to updated guidelines that abandon targeting RAI or CIRCI. Recent studies with an RAI mouse model showed a clear survival benefit from GC therapy in mice with RAI, suggesting that inconclusive GC clinical trials might be due to issues with the ACTH test rather than targeting RAI. To investigate, we performed the ACTH test in septic mice. Interestingly, the ACTH test identified most mice as having adrenal insufficiency in early and middle stages of sepsis, even those with a normal adrenal stress response. Surprisingly, the ACTH test increased inflammatory cytokines to lethal levels, moderately increasing mortality in septic mice. This study revealed significant flaws in the ACTH test for diagnosing RAI/CIRCI. It not only fails to correctly identify these conditions, leading to misguided use of GCs, but also induces a lethal inflammatory response in sepsis. These findings suggest that inconclusive GC therapy trials may be due to the problematic nature of the ACTH test rather than ineffectiveness of targeting RAI/CIRCI.

Chronic inflammation is mainly characterized by the release of proinflammatory cytokines (cytokine storm) and reactive oxygen/nitrogen species. Sepsis is a life-threatening condition resulting from the successive chronic inflammatory responses toward infection, leading to multiple organ failure and, ultimately, death. As inflammation and oxidative stress are known to nourish each other and initiate an uncontrolled immune response, inhibiting the cross-talk between the inflammatory response using anti-inflammatory drugs and oxidative stress using antioxidants can be a promising strategy to target sepsis. Here, we present the engineering of chimeric nanomicelles (NMs) using an ester-linked polyethylene glycol-derived lithocholic acid-drug conjugate using dexamethasone (DEX), a potent glucocorticoid possessing anti-inflammatory properties, and vitamin E (VITE), an antioxidant to target oxidative stress. Interestingly, these chimeric DEX-VITE NMs show enhanced accumulation at the inflamed sites driven by enhanced permeation and retention effect and mitigate localized acute inflammation in paw, lung, and liver inflammation models. We further demonstrated the efficacy of these NMs in mitigating LPS-induced endotoxemia and CLP-induced microbial sepsis, conferring survival advantages. DEX-VITE NMs also modulate immune homeostasis by decreasing the infiltration of total immune cells, neutrophils, and overall macrophages. Finally, administration of DEX-VITE NMs also reduces the release of proinflammatory cytokines and prevents vascular damage, two critical factors of sepsis pathogenesis. Therefore, this therapeutic approach of chimeric NMs can effectively deliver steroids and antioxidants to mitigate uncontrolled localized and systemic inflammation.

For the medical diagnosis of sepsis, it is crucial to differentiate infectious inflammation from noninfectious symptoms to prevent acute aggravation. Herein, a diagnosis for early stage sepsis was performed using LPC 16:0 and total phospholipids as small molecular biomarkers. The measurement of LPC 16:0 was conducted using a parylene matrix chip, which was developed to effectively detect small molecules in laser desorption/ionization mass spectrometry (LDI-MS). Meanwhile, the total phospholipid level was measured using colorimetry, following an enzymatic assay. Next, the two biomarkers were analyzed in serum samples from healthy volunteers, systemic inflammatory response syndrome (SIRS) patients, and sepsis patients. Diagnostic criteria were established based on the biomarker intensities observed in each patient group. After the measurements were conducted, the interference in phospholipid analysis due to hemoglobin contamination was considered. Additionally, the analytical parameters from biomarker detection were statistically interpreted and compared with those of conventional diagnostic standards. Finally, the diagnostic performance of each biomarker was evaluated by analyzing the biomarker levels between patient groups and examining their overlapping extents in box plots to distinguish sepsis from noninfectious inflammatory symptoms.

One of the essential factors in the appropriate treatment of infections is accurate and timely laboratory diagnosis. The correct diagnosis of infections plays a vital role in determining desirable therapy and controlling the spread of pathogens. Traditional methods of infection diagnosis are limited by several factors such as insufficient sensitivity and specificity, being time-consuming and laborious, having a low ability to distinguish infection from non-infectious inflammatory conditions and a low potential to predict treatment outcomes. Therefore, it is necessary to find innovative strategies for detecting specific biomarkers in order to diagnose infections. The rapid advancement of metabolomics makes it possible to determine the pattern of metabolite changes in the both of pathogen and the host during an infection. Metabolomics is a method used to assess the levels and type of metabolites in an organism. Metabolites are of low-molecular-weight compounds produced as a result of metabolic processes and pathways within cells. Metabolomics provides valuable data to detect accurate biomarkers of specific biochemical features directly related to certain phenotypes or conditions. This study aimed to review the applications and progress of metabolomics as a biomarker for the diagnosis of bacterial infections.

In this article, we present the first instance of depositing WTex-sensitive films with varying thicknesses (3, 4, and 5 nm) onto flexible polyimide substrates using radio-frequency sputtering. These films were used to create an extended-gate field-effect transistor (EGFET) for pH sensing and detecting procalcitonin (PCT) in the sera of patients with sepsis or bacterial infections. Among the films, the 4 nm WTex film exhibited high sensitivity (59.57 mV/pH), minimal hysteresis (∼0.8 mV), and a low drift rate (0.14 mV/h). Additionally, this WTex-based EGFET sensor retained a pH sensitivity of 59.2 mV/pH even after 180 days of operation and exhibited excellent mechanical flexibility, enduring 500 bending cycles without degradation. Moreover, PCT antibodies, activated using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide and N-hydroxysuccinimide, were immobilized on the WTex film functionalized with 3-aminopropyl triethoxysilane. This effective immobilization enabled the specific binding of PCT antigens. The WTex-based EGFET biosensor demonstrated high sensitivity (18.12 mV/pCPCT) across a wide dynamic range (1 fg/mL to 1 μg/mL). Furthermore, the PCT concentrations in patient sera, whether from individuals with or without sepsis or bacterial infections, measured by our biosensor were comparable to results obtained using clinical enzyme-linked immunosorbent assay kits.

To investigate the potential and evolving trends in fluid management for patients with sepsis, utilizing a bibliometric approach.

Scholarly articles pertaining to fluid therapy for sepsis patients were extracted from the Web of Science (WoS) database as of June 1, 2024. The R software package, "Bibliometrix," was utilized to scrutinize the primary bibliometric attributes and to construct a three-field plot to illustrate the relationships among institutions, nations, and keywords. The VOSviewer tool was employed for author analysis, keyword co-occurrence analysis, and data visualization. Additionally, CiteSpace was used to calculate citation bursts and keywords.

A comprehensive retrieval from the Web of Science (WoS) database yielded a total of 2,569 publications. The majority of these articles were predominantly published by two countries, namely the United States (US) and China. Among the myriad of journals, Critical Care and Journal for Intensive Care Medicine emerged as the most prolific. In terms of institutional contribution, the University of California System stood out as the most productive. Recent analysis of keywords revealed a significant citation burst for terms such as "balanced crystalloids" and "critically ill children".

There is a growing focus on the connection between fluid management and the treatment of sepsis, with research in this area being at an advanced stage.

Sepsis, a systemic inflammatory response syndrome resulting from an uncontrolled inflammatory reaction to infection, remains without a definitive cure despite therapeutic advancements. Mesenchymal stem cells (MSCs), renowned for their capacity to alleviate inflammation and modulate the immune system, have emerged as a potential treatment avenue for sepsis. In sepsis pathophysiology, hyperactivated neutrophils release extracellular neutrophil traps (NETs). NETs are essential for eradicating pathogens; however, excessive formation leads to tissue damage. Given the limited knowledge regarding the impact of NETs on MSCs used in sepsis therapy and the established interaction between MSCs and NETs, this study investigates the effects of NETs on MSCs in vitro. NETs were isolated from stimulated neutrophils, and MSCs were sourced from umbilical cord blood. After co-culturing MSCs with isolated NETs, MSCs' viability, migration, intracellular antioxidant capacity, and changes in gene expression were analyzed. Following exposure to NETs, MSCs exhibited obvious apoptosis and necrosis. NETs disrupt MSCs' mitochondrial activity. Also, NETs upregulate the pro-apoptotic gene BAX and downregulate the anti-apoptotic gene BCL2 in MSCs. Additionally, NETs reduce MSCs' intracellular antioxidant capacity. Furthermore, MSC migration is significantly impaired by NETs. This study collectively demonstrates that NETs have toxic and detrimental effects on MSCs. These effects on MSCs indicate a potential barrier to their functionality and therapeutic efficacy. Therefore, it appears that reducing the undesirable effects of NETs could serve as a novel target to enhance the therapeutic efficacy of MSCs in septic patients.

Despite recent advances and global improvements in sepsis recognition and supportive care, mortality rates remain high, and adherence to sepsis bundle components in Korea is low. To address this, the Korean Sepsis Alliance, affiliated with the Korean Society of Critical Care Medicine, developed the first sepsis treatment guidelines for Korea based on a comprehensive systematic review and meta-analysis.

A de novo method was used to develop the guidelines. Methodologies included determining key questions, conducting a literature search and selection, assessing the risk of bias, synthesizing evidence, and developing recommendations. The certainty of evidence and the strength of recommendations were determined using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Draft recommendations underwent internal and external review processes and public hearings. The development of these guidelines was supported by a research grant from the Korean Disease Control and Prevention Agency.

In these guidelines, we focused on early treatments for adult patients with sepsis and septic shock. Through the guideline development process, 12 key questions and their respective recommendations were formulated. These include lactate measurement, fluid therapies, target blood pressure, antibiotic administration, use of vasopressors and dobutamine, extracorporeal membrane oxygenation, and echocardiography.

These guidelines aim to support medical professionals in making appropriate decisions about treating adult sepsis and septic shock. We hope these guidelines will increase awareness of sepsis and reduce its mortality rate.

Sepsis is associated with an approximately 20 % 30-day readmission rate and with subsequent mortality.

To determine the demographics, comorbidities that had been documented prior to sepsis onset, processes of care, commonly administered laboratory tests measured near discharge, and post-sepsis infections that may be associated with readmission and, secondarily, whether readmission is an independent risk factor for 90-day mortality.

Using a database of patients who met Sepsis-3 criteria divided into Construction and Validation groups, we used logistic regression to estimate the factors independently associated with readmission within 30 days after discharge and proportional hazard regression to estimate the factors independently associated with 90-day mortality.

Of the 30,798 patients ≥ 18 years at our combined referral and community hospital and were discharged alive who met Sepsis-3 criteria between July 10, 2009 and September 7, 2019, 5943 (19 %) were readmitted within 30 days. Thirteen thousand, four hundred forty-four (44 %) of the patients were female, 25,293 (82 %) White, 3523 (11 %) Black, and the mean age was 59 ± 17 years. Among the readmitted patients, 894 (15 %) died within 90 days from the original discharge compared to 11 % (p < 0.001) who had not been readmitted. Seven comorbidities, five processes of care (presepsis platelet transfusion, postsepsis platelet transfusion, operation, ICU length of stay, and hospital length of stay), five culture results, two discharge laboratory values, and discharge location were associated with readmission. The model had good discrimination, 0.770 ± 0.004 (Construction Group) and 0.748 ± 0.006 (Validation Group) and good relevancy (area under the precision recall curve), 0.390 ± 0.004 (Construction group) and 0.476 ± 0.005 (Validation group). Readmission within 30 days was independently associated with a 56 % higher risk of death (HR=1.562, 95 % CI=1.434, 1.703, p < 0.001) within 90 days from discharge.

Comorbidities, abnormal laboratory values, processes of care, and post-sepsis onset culture results, but not demographic characteristics, were associated with 30-day readmission. Readmission was associated with 90-day mortality.

To evaluate the appropriateness of empiric initiation of meropenem in the intensive care unit (ICU) and to determine the agreement between internal medicine (IM) residents and infectious diseases (ID) physicians/pharmacists on appropriateness.

Retrospective observational study.

ICU in a tertiary care community teaching hospital.

Adult patients admitted to the ICU and started empirically on meropenem between April 1 and October 31, 2021.

Meropenem usage was categorized as appropriate or inappropriate according to criteria developed from previously published indications and modified by ID physicians/pharmacists to reflect local practices. Two investigators (an IM resident and either an ID physician or pharmacist) assessed the appropriateness, with a second ID physician resolving any disagreements. Inter-rater reliability was measured using the kappa statistic.

Ninety-seven participants were enrolled, with a mean age of 68 (SD, 17.0) years. Pneumonia was the most common infection (30.9%). Among the participants, 92.8% received an ID consultation, with 55.6% of these occurring before meropenem initiation. IM residents deemed 56.7% of meropenem administrations appropriate, whereas an ID physician/pharmacist deemed only 48.5% appropriate, agreeing on 79.4% of cases (kappa statistic 0.59, P <.001). After a third reviewer's assessment was included, agreement between the resident and at least one of the two reviewers reached 90.7% (kappa 0.81, P <.001).

Approximately half of empiric meropenem started in the ICU was deemed inappropriate using institution-specific criteria. There was good agreement between IM residents and ID physicians/pharmacists on meropenem appropriateness. IM residents could contribute to antimicrobial stewardship efforts, like prospective audit and feedback, using standardized criteria for appropriateness.

Diagnostic errors affect patient management, and as blood gas analysis is mainly performed without the laboratory, users must be aware of the potential pitfalls. The aim was to provide a summary of common issues users should be aware of.A narrative review was performed using online databases such as PubMed, Google Scholar and reference lists of identified papers. Language was limited to English.Errors can be pre-analytical, analytical or post-analytical. Samples should be analysed within 15 min and kept at room temperature and taken at least 15-30 min after changes to inspired oxygen and ventilator settings, for accurate oxygen measurement. Plastic syringes are more oxygen permeable if chilled. Currently, analysers run arterial, venous, capillary and intraosseous samples, but variations in reference intervals may not be appreciated or reported. Analytical issues can arise from interference secondary to drugs, such as spurious hyperchloraemia with salicylate and hyperlactataemia with ethylene glycol, or pathology, such as spurious hypoxaemia with leucocytosis and alkalosis in hypoalbuminaemia. Interpretation is complicated by result adjustment, for example, temperature (alpha-stat adjustment may overestimate partial pressure of carbon dioxide (pCO2) in hypothermia, for example), and inappropriate reference intervals, for example, in pregnancy bicarbonate, and pCO2 ranges should be lowered.Lack of appreciation for patient-specific and circumstance-specific reference intervals, including extremes of age and altitude, and transformation of measurements to standard conditions can lead to inappropriate assumptions. It is vitally important for users to optimise specimen collection, appreciate the analytical methods and understand when reference intervals are applicable to their specimen type, clinical question or patient.

Transverse colon volvulus is an uncommon cause of large bowel obstruction, often presenting as a surgical emergency. This case report details a rare instance of gangrenous transverse colon volvulus in a 50-year-old male patient with a history of Hartmann's procedure performed six years prior.

The patient presented with acute abdominal pain, diffuse abdominal distension, and failure to pass feces and flatus. An emergency laparotomy was performed, revealing a gangrenous segment of the transverse colon. Despite surgical intervention, the patient died due to Multi organ failure (MOF).

A patient diagnosed with transverse colon volvulus typically presents with colicky abdominal pain, vomiting, constipation or obstipation, and abdominal distension. Physical signs may include abdominal distention, a palpable mass, circulatory collapse, fever, and leukocytosis.

This case underscores the importance of early recognition and prompt surgical intervention in managing transverse colon volvulus.

Background: Early prediction of sepsis onset is crucial for reducing mortality and the overall cost burden of sepsis treatment. Currently, few effective and accurate prediction tools are available for sepsis. Hence, in this study, we developed an effective sepsis clinical decision support system (S-CDSS) to assist emergency physicians to predict sepsis. Methods: This study included patients who had visited the emergency department (ED) of Taipei Tzu Chi Hospital, Taiwan, between January 1, 2020, and June 31, 2022. The patients were divided into a derivation cohort (n = 70,758) and a validation cohort (n = 27,545). The derivation cohort was subjected to 6-fold stratified cross-validation, reserving 20% of the data (n = 11,793) for model testing. The primary study outcome was a sepsis prediction ( International Classification of Diseases , Tenth Revision , Clinical Modification ) before discharge from the ED. The S-CDSS incorporated the LightGBM algorithm to ensure timely and accurate prediction of sepsis. The validation cohort was subjected to multivariate logistic regression to identify the associations of S-CDSS-based high- and medium-risk alerts with clinical outcomes in the overall patient cohort. For each clinical outcome in high- and medium-risk patients, we calculated the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and accuracy of S-CDSS-based predictions. Results: The S-CDSS was integrated into our hospital information system. The system featured three risk warning labels (red, yellow, and white, indicating high, medium, and low risks, respectively) to alert emergency physicians. The sensitivity and specificity of the S-CDSS in the derivation cohort were 86.9% and 92.5%, respectively. In the validation cohort, high- and medium-risk alerts were significantly associated with all clinical outcomes, exhibiting high prediction specificity for intubation, general ward admission, intensive care unit admission, ED mortality, and in-hospital mortality (93.29%, 97.32%, 94.03%, 93.04%, and 93.97%, respectively). Conclusion: Our findings suggest that the S-CDSS can effectively identify patients with suspected sepsis in the ED. Furthermore, S-CDSS-based predictions appear to be strongly associated with clinical outcomes in patients with sepsis.

To evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion.

This study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization.

A total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P=0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days-6.0 days vs. median=5.0 days, IQR: 3.0 days-8.0 days, respectively; P=0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3-2.0 mmol/L vs. median=0.0 mmol/L, IQR: -0.2 to 0.8 mmol/L, respectively; P <0.001) and 24 h (median=1.4 mmol/L, IQR: 0.3-2.2 mmol/L vs. median=0.4 mmol/L, IQR: -0.4 to 1.6 mmol/L, respectively; P=0.001).

SFI plus standard therapy did not significantly decrease 28-day all-cause mortality for septic patients with hypoperfusion and TCM syndrome with Yang-Qi deficiency.Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR1800020435.

Sepsis is a life-threatening syndrome resulting from a dysregulated host response to infection. It is the primary cause of death in the intensive care unit, posing a substantial challenge to human health and medical resource allocation. The pathogenesis and pathophysiology of sepsis are complex. During its onset, pro-inflammatory and anti-inflammatory mechanisms engage in intricate interactions, possibly leading to hyperinflammation, immunosuppression, and long-term immune disease. Of all critical outcomes, hyperinflammation is the main cause of early death among patients with sepsis. Therefore, early suppression of hyperinflammation may improve the prognosis of these patients. Nafamostat mesilate is a serine protease inhibitor, which can inhibit the activation of the complement system, coagulation system, and contact system. In this review, we discuss the pathophysiological changes occurring in these systems during sepsis, and describe the possible targets of the serine protease inhibitor nafamostat mesilate in the treatment of this condition.

Sepsis is a severe immune response to an infection. It is associated with multiple organ dysfunction syndrome (MODs) along with systemic and neuronal inflammatory response. This study focused on the acute neurologic dysfunction associated with sepsis by exploring the role of PPARγ/SIRT1 pathway against sepsis. We studied the role of this axis in ameliorating sepsis-associated encephalopathy (SAE) and its linked neurobehavioral disorders by using pioglitazone (PIO). This PPARγ agonist showed neuroprotective actions in neuroinflammatory disorders. Sepsis was induced in mice by LPS (10 mg/kg). Survival rate and MODs were assessed. Furthermore, behavioral deficits, cerebral oxidative, inflammatory, and apoptotic markers, and the cerebral expression level of SIRT1 were determined. In this study, we observed that PIO attenuated sepsis-induced cerebral injury. PIO significantly enhanced survival rate, attenuated MODs, and systemic inflammatory response in septic mice. PIO also promoted cerebral SIRT1 expression and reduced cerebral activation of microglia, oxidative stress, HMGB, iNOS, NLRP3 and caspase-3 along with an obvious improvement in behavioral deficits and cerebral pathological damage induced by LPS. Most of the neuroprotective effects of PIO were abolished by EX-527, a SIRT1 inhibitor. These results highlight that the neuroprotective effect of PIO in SAE is mainly SIRT1-dependent.

This study investigated the occurrence and dynamics of oral Staphylococcus species in patients with orofacial clefts undergoing surgical rehabilitation treatment. Patients (n = 59) were statistically stratified and analyzed (age, gender, types of orofacial clefts, surgical history, and types of previous surgical rehabilitation). Salivary samples were obtained between hospitalization and the return to the specialized medical center. Microbiological diagnosis was performed by classical methods, and MALDI-TOF MS. MRSA strains (SCCmec type II, III, and IV) were characterized by the Decision Tree method. A total of 33 (55.9%) patients showed oral staphylococcal colonization in one, two, or three sampling steps. A high prevalence has been reported for S. aureus (including HA-, MRSA and CA-MRSA), followed by S. saprophyticus, S. epidermidis, S. sciuri, S. haemolyticus, S. lentus, S. arlettae, and S. warneri. The dynamics of oral colonization throughout surgical treatment and medical follow-up may be influenced by (i) imbalances in staphylococcal maintenance, (ii) efficiency of surgical asepsis or break of the aseptic chain, (iii) staphylococcal neocolonization in newly rehabilitated anatomical oral sites, and (iv) total or partial maintenance of staphylococcal species. The highly frequent clinical periodicity in specialized medical and dental centers may contribute to the acquisition of MRSA in these patients.

The orthotopic ileal neobladder is becoming a popular technique of urinary diversion after radical cystectomy (RC) for localized muscle-invasive bladder cancer (MIBC), allowing patient continence, with a more desirable body image and good quality of life. Minimally invasive robot-assisted RC and neobladder have the potential to minimize physical and psychological trauma and are increasingly being adopted for patients with MIBC worldwide. Spontaneous perforation of orthotopic neobladder is uncommon;however, it represents serious complications. Solitary binge drinking can be dangerous in a patient with a neobladder because of reduced level of consciousness and overdistension of the neobladder. We report a case of spontaneous ileal neobladder perforations one year post-robotic RC secondary to blackouts from binge drinking. We also describe nonoperative active management and review the literature. A 66-year-old gentleman was brought by ambulance to our emergency department with a reduced level of consciousness, vomiting, and abdominal pain in the early hours of the morning. Collateral history revealed that he had drunk alcohol alone the night before at his home where he lives alone. Initial examination revealed tachycardia and hypotension. Immediate resuscitation using the sepsis six protocol included intravenous normal saline, blood culture, broad-spectrum antibiotic, lactate measurement, and insertion of a urethral catheter to monitor urine output. Following contrast-enhanced computed tomography (CECT) of the abdomen and pelvis, the patient was referred to a urologist. A diagnosis of spontaneous perforation of the neobladder was made. A nonoperative or 'conservative' management approach was adopted with careful active monitoring at the intensive care unit (ICU) involving a multidisciplinary team. Follow-up CT was performed to assess radiological recovery. The patient recovered successfully and was discharged home five weeks post-admission with an indwelling urethral catheter. The catheter was removed 10 weeks post-admission following a cystogram confirming the integrity of the neobladder. The patient has preserved neobladder function and continence and is doing well until the last follow-up at six months post-discharge. Patients with neobladder should be rigorously counseled about the importance of timed voiding, intermittent self-catheter, serious consequences of solitary binge drinking, and urinary retention.

Pediatric sepsis remains a leading cause of childhood morbidity and mortality worldwide. Despite advancements in modern medicine, it accounts for more than 3 million childhood deaths per year. Multiple studies have emphasized that sex and gender have an impact on the treatment and outcome of various diseases. Adult studies have revealed sex differences in pathophysiological responses to septic shock, as well as a possible protective effect of estrogens on critical illness. Sex-specific maturational and developmental differences in host immunology have been previously demonstrated for neonatal and pediatric age groups. At present, there are no studies assessing the impact of sex on outcomes of children with sepsis.

The goal of this study is to assess sex-specific differences in childhood sepsis survival outcomes. We will systematically assess associations of sex and gender with outcomes in pediatric sepsis in the literature by performing a systematic search of MEDLINE and Embase databases. We will include all English language randomized trials and cohort studies. The study population will include children > 37 weeks gestational age and < 18 years of age. Exposure will be sepsis, severe sepsis, and septic shock and the main comparison will be between male and female sex. The primary outcome will be hospital mortality. Secondary outcomes will be the pediatric intensive care unit and hospital length of stay.

Results from this review are expected to provide important information on the association of sex with the outcomes of pediatric sepsis. If an association is noted, this study may serve as a foundation for further research evaluating the pathophysiological aspects as well as potential socioeconomic factors responsible for the clinically detected sex differences.

PROSPERO CRD42022315753.

The acute respiratory distress syndrome (ARDS) is a common complication of severe COVID-19 and contributes to patient morbidity and mortality. ARDS is a heterogeneous syndrome caused by various insults, and results in acute hypoxemic respiratory failure. Patients with ARDS from COVID-19 may represent a subgroup of ARDS patients with distinct molecular profiles that drive disease outcomes. Here, we hypothesized that longitudinal transcriptomic analysis may identify distinct dynamic pathobiological pathways during COVID-19 ARDS.

We identified a patient cohort from an existing ICU biorepository and established three groups for comparison: 1) patients with COVID-19 ARDS that survived hospitalization (COVID survivors, n = 4), 2) patients with COVID-19 ARDS that did not survive hospitalization (COVID non-survivors, n = 5), and 3) patients with ARDS from other causes as a control group (ARDS controls, n = 4). RNA was isolated from peripheral blood mononuclear cells (PBMCs) at 4 time points (Days 1, 3, 7, and 10 following ICU admission) and analyzed by bulk RNA sequencing.

We first compared transcriptomes between groups at individual timepoints and observed significant heterogeneity in differentially expressed genes (DEGs). Next, we utilized the likelihood ratio test to identify genes that exhibit different patterns of change over time between the 3 groups and identified 341 DEGs across time, including hemoglobin subunit alpha 2 (HBA1, HBA2), hemoglobin subunit beta (HBB), von Willebrand factor C and EGF domains (VWCE), and carbonic anhydrase 1 (CA1), which all demonstrated persistent upregulation in the COVID non-survivors compared to COVID survivors. Of the 341 DEGs, 314 demonstrated a similar pattern of persistent increased gene expression in COVID non-survivors compared to survivors, associated with canonical pathways of iron homeostasis signaling, erythrocyte interaction with oxygen and carbon dioxide, erythropoietin signaling, heme biosynthesis, metabolism of porphyrins, and iron uptake and transport.

These findings describe significant differences in gene regulation during patient ICU course between survivors and non-survivors of COVID-19 ARDS. We identified multiple pathways that suggest heme and red blood cell metabolism contribute to disease outcomes. This approach is generalizable to larger cohorts and supports an approach of longitudinal sampling in ARDS molecular profiling studies, which may identify novel targetable pathways of injury and resolution.

The autonomic nervous system plays a key role in maintaining body hemostasis through both the sympathetic and parasympathetic nervous systems. Sympathetic overstimulation as a reflex to multiple pathologies, such as septic shock, brain injury, cardiogenic shock, and cardiac arrest, could be harmful and lead to autonomic and immunologic dysfunction. The continuous stimulation of the beta receptors on immune cells has an inhibitory effect on these cells and may lead to immunologic dysfunction through enhancing the production of anti-inflammatory cytokines, such as interleukin-10 (IL-10), and inhibiting the production of pro-inflammatory factors, such as interleukin-1B IL-1B and tissue necrotizing factor-alpha (TNF-alpha). Sympathetic overstimulation-induced autonomic dysfunction may also happen due to adrenergic receptor insensitivity or downregulation. Administering anti-adrenergic medication, such as beta-blockers, is a promising treatment to compensate against the undesired effects of adrenergic surge. Despite many misconceptions about beta-blockers, beta-blockers have shown a promising effect in decreasing mortality in patients with critical illness. In this review, we summarize the recently published articles that have discussed using beta-blockers as a promising treatment to decrease mortality in critically ill patients, such as patients with septic shock, traumatic brain injury, cardiogenic shock, acute decompensated heart failure, and electrical storm. We also discuss the potential pathophysiology of beta-blockers in various types of critical illness. More clinical trials are encouraged to evaluate the safety and effectiveness of beta-blockers in improving mortality among critically ill patients.

A commonly used guideline for community-acquired pneumonia (CAP) is the joint American Thoracic Society and Infectious Diseases Society of America practice guideline. We aimed to investigate the effect of guideline-concordant therapy in the treatment of CAP.

We systematically searched MEDLINE, Embase, CENTRAL, Web of Science, and Scopus from 2007 to December 2023. We screened citations, extracted data, and assessed risk of bias in duplicate. Primary outcomes were mortality rates, intensive care unit (ICU) admission, and length of stay. Secondary outcomes were guideline adherence, readmission, clinical cure rate, and adverse complications. We performed random-effect meta-analysis to estimate the overall effect size and assessed heterogeneity using the I2 statistics.

We included 17 observational studies and 82 240 patients, of which 10 studies were comparative and pooled in meta-analysis. Overall guideline adherence rate was 65.2%. Guideline-concordant therapy was associated with a statistically significant reduction in 30-day mortality rate (crude odds ratio [OR], 0.49 [95% confidence interval .34-.70; I2 = 60%]; adjusted OR, 0.49 [.37-.65; I2 = 52%]) and in-hospital mortality rate (crude OR, 0.63 [.43-.92]; I2 = 61%). Due to significant heterogeneity, we could not assess the effect of guideline-concordant therapy on length of stay, ICU admission, readmission, clinical cure rate, and adverse complications.

In hospitalized patients with CAP, guideline-concordant therapy was associated with a significant reduction in mortality rate compared with nonconcordant therapy; however, there was limited evidence to support guideline-concordant therapy for other clinical outcomes. Future studies are needed to assess the clinical efficacy and safety of current guideline recommendations.

Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily broad in retrospect, and whether these patterns are changing over time.

To describe trends in empiric broad-spectrum antibiotic use for suspected community-onset sepsis.

This cross-sectional study used clinical data from adults admitted to 241 US hospitals in the PINC AI Healthcare Database. Eligible participants were aged 18 years or more and were admitted between 2017 and 2021 with suspected community-onset sepsis, defined by a blood culture draw, lactate measurement, and intravenous antibiotic administration on admission.

Empiric anti-methicillin-resistant Staphylococcus aureus (MRSA) and/or antipseudomonal β-lactam agent use.

Annual rates of empiric anti-MRSA and/or antipseudomonal β-lactam agent use and the proportion that were likely unnecessary in retrospect based on the absence of β-lactam resistant gram-positive or ceftriaxone-resistant gram-negative pathogens from clinical cultures obtained through hospital day 4. Annual trends were calculated using mixed-effects logistic regression models, adjusting for patient and hospital characteristics.

Among 6 272 538 hospitalizations (median [IQR] age, 66 [53-78] years; 443 465 male [49.6%]; 106 095 Black [11.9%], 65 763 Hispanic [7.4%], 653 907 White [73.1%]), 894 724 (14.3%) had suspected community-onset sepsis, of whom 582 585 (65.1%) received either empiric anti-MRSA (379 987 [42.5%]) or antipseudomonal β-lactam therapy (513 811 [57.4%]); 311 213 (34.8%) received both. Patients with suspected community-onset sepsis accounted for 1 573 673 of 3 141 300 (50.1%) of total inpatient anti-MRSA antibiotic days and 2 569 518 of 5 211 745 (49.3%) of total antipseudomonal β-lactam days. Between 2017 and 2021, the proportion of patients with suspected sepsis administered anti-MRSA or antipseudomonal therapy increased from 63.0% (82 731 of 131 275 patients) to 66.7% (101 003 of 151 435 patients) (adjusted OR [aOR] per year, 1.03; 95% CI, 1.03-1.04). However, resistant organisms were isolated in only 65 434 cases (7.3%) (30 617 gram-positive [3.4%], 38 844 gram-negative [4.3%]) and the proportion of patients who had any resistant organism decreased from 9.6% to 7.3% (aOR per year, 0.87; 95% CI, 0.87-0.88). Most patients with suspected sepsis treated with empiric anti-MRSA and/or antipseudomonal therapy had no resistant organisms (527 356 of 582 585 patients [90.5%]); this proportion increased from 88.0% in 2017 to 91.6% in 2021 (aOR per year, 1.12; 95% CI, 1.11-1.13).

In this cross-sectional study of adults admitted to 241 US hospitals, empiric broad-spectrum antibiotic use for suspected community-onset sepsis accounted for half of all anti-MRSA or antipseudomonal therapy; the use of these types of antibiotics increased between 2017 and 2021 despite resistant organisms being isolated in less than 10% of patients treated with broad-spectrum agents.

The adrenal gland is a vital endocrine organ, and adrenal steroid synthesis and secretion are closely regulated by the hypothalamic-pituitary-adrenal (HPA) axis in response to various stimuli. Surgery or trauma can activate the HPA axis and induce the secretion of cortisol. Different cortisol responses vary with the grade of surgery. Perioperative medications have the potential to decrease the cortisol level in the body, and both excessive and insufficient cortisol levels after surgery are disadvantageous. The effect of perioperative medications on the HPA response to surgery can be divided into three levels: "adrenal insufficiency (AI)", "stress response inhibition", and "uncertainty". The clinical presentation of AI includes fatigue, nausea, vomiting, abdominal pain, muscle cramps, hypotension, hypovolemic shock and prerenal failure, which may result in fatal consequences. Stress response inhibition can reduce postoperative complications, such as pain and cognitive dysfunction. This is protective to patients during perioperative and postoperative periods. The aim of the present review is to shed light on current evidence regarding the exact effects and mechanisms of perioperative medications on the HPA response to surgical injury and provide the applicable guidance on clinical anesthesia.

In this retrospective pharmacovigilance study, we gathered data on drug-induced posterior reversible encephalopathy syndrome (PRES). Our goal was to identify the primary suspect drugs in PRES by analyzing the Food and Drug Administration Adverse Events Reporting System (FAERS) database.

We identified and analyzed reports of PRES listed in the FAERS database between 2004 and 2021. Using the reporting odds ratio and 95% confidence interval, we evaluated the safety signals for each of the drugs associated with PRES.

We reviewed 11,077 reports of adverse events corresponding to PRES. The primary suspect drug categories were antineoplastics, immunosuppressants, and glucocorticoids. PRES was 24.77% more likely to occur in females than in males. Drug-induced PRES usually occurs in individuals with cancer, those who have undergone an organ/stem cell transplant, and those with autoimmune conditions.

Our results show that the drugs most commonly suspected to cause PRES were antineoplastics, immunosuppressants, and glucocorticoids. Future studies are needed to illuminate the pathophysiological alterations that underlie PRES. In the meantime, prescribers and patients should be made aware of the potential risks of PRES associated with pharmaceutical therapy, and the summaries of product characteristics for individual drugs should be updated to include this information.

There is a lack of evidence-based guidelines for the administration methods of ceftriaxone in emergency departments (EDs), resulting in the reliance on individual institutional protocols for decision-making.

This study was performed to compare the effects of administering ceftriaxone via intravenous push (IVP) and intravenous piggyback (IVPB) on 28-day mortality in patients with sepsis.

This was a retrospective study of patients aged 18 years or older with sepsis or septic shock who visited an ED and were treated with ceftriaxone as an initial antibiotic between March 2010 and February 2019. Patients were divided into the IVP group and the IVPB group based on the administration method. The primary outcome was 28-day mortality, and multivariable Cox proportional hazards regression analysis was performed to evaluate the relationship between antibiotic administration methods and 28-day mortality.

During the study period, a total of 939 patients were included in the final analysis, and the overall mortality rate was 12.2%. The antibiotic administration time was significantly lower in the IVP group than in the IVPB group, and the rates of antibiotic administration within 1 h and within 3 h were higher in the IVP group than in the IVPB group (p < 0.05). However, there was no significant difference in 28-day mortality between the two groups (hazard ratio 1.07, 95% confidence interval 0.69-1.65).

IVP administration of ceftriaxone reduced the time of antibiotic administration compared with IVPB, but there was no difference in 28-day mortality.

To compare the clinical outcomes of intensive glucose control and liberal glucose control for septic patients in intensive care unit.

The databases of PubMed, Cochrane Library, Embase and Web of Science were searched systematically from inception to November 27, 2023 to identify trials involving a randomized comparison between intensive and liberal glucose control for septic patients in intensive care unit.

A total of 14 randomized controlled trials involving 6226 patients were finally included. There was no statistically significant difference observed between intensive glucose control and liberal glucose control in terms of all-cause mortality, the need for renal replacement, vasopressor-free and mechanical ventilation-free days, and length of hospital stay. However, it is noteworthy that intensive glucose control exhibited a statistically higher risk of severe hypoglycemia (RR 2.66; 95%CI 1.85 to 3.83), need for blood transfusion (RR 1.12; 95%CI 1.01 to 1.23), and statistically prolonged length of stay in the ICU (MD 1.67; 95%CI 0.22 to 3.12) compared to liberal glucose control. Nevertheless, sensitivity analysis revealed that the need for blood transfusion and length of stay in the intensive care unit were not robust.

Both intensive and liberal glucose control had comparable effects on improving patient outcomes, but intensive glucose control carried a higher risk of severe hypoglycemia.

In this study, a murine sepsis model was developed using the cecum ligation and puncture (CLP) technique. The expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in the brain increased 6 h after CLP but decreased 24 h later when elevated endogenous dopamine levels in the brain were sustained. Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride reduced dopamine levels in the striatum and increased mortality in septic mice. Dopamine D1-like receptors were significantly expressed in the brain, but not in the lungs. Intraperitoneally administered SKF-81297 (SKF), a blood-brain barrier-permeable D1-like receptor agonist, prevented CLP-induced death of septic mice with ameliorated acute lung injury and cognitive dysfunction and suppressed TNF-α and IL-1β expression. The D1-like receptor antagonist SCH-23390 abolished the anti-inflammatory effects of SKF. These data suggest that D1-like receptor-mediated signals in the brain prevent CLP-induced inflammation in both the brain and the periphery.

Patients with peripheral artery disease (PAD) have increased mortality rates and a myopathy in their affected legs which is characterized by increased oxidative damage, reduced antioxidant enzymatic activity and defective mitochondrial bioenergetics. This study evaluated the hypothesis that increased levels of oxidative damage in gastrocnemius biopsies from patients with PAD predict long-term mortality rates. Oxidative damage was quantified as carbonyl adducts in myofibers of the gastrocnemius of PAD patients. The oxidative stress data were grouped into tertiles and the 5-year, all-cause mortality for each tertile was determined by Kaplan-Meier curves and compared by the Modified Peto test. A Cox-regression model was used to control the effects of clinical characteristics. Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities. Of the 240 study participants, 99 died during a mean follow up of 37.8 months. Patients in the highest tertile of oxidative damage demonstrated the highest 5-year mortality rate. The mortality hazard ratios (HR) from the Cox analysis were statistically significant for oxidative damage (lowest vs middle tertile; HR = 6.33; p = 0.0001 and lowest vs highest; HR = 8.37; p < 0.0001). Survival analysis of a contemporaneous population of PAD patients identifies abundance of carbonyl adducts in myofibers of their gastrocnemius as a predictor of mortality rate independently of ankle-brachial index, disease stage and other clinical and myopathy-related covariates.

Fluid resuscitation of patients with sepsis is crucial. This study explored the role of fluid balance in the early resuscitation of sepsis patients in the intensive care unit (ICU).

A retrospective study of patients with sepsis using the Peking Union Medical College Hospital Intensive Care Medical Information System and Database from January 2014 to June 2020 was performed. Based on the survival status on day 28, the training cohort was divided into an alive group (n = 1,803) and a deceased group (n = 429). Univariate and multivariate analyses were used to identify risk factors, and the integrated learning XGBoost algorithm was used to construct a model for predicting outcomes. ROC and Kaplan-Meier survival curves were used to evaluate the effectiveness of the model. A verification cohort (n = 433) was used to verify the model.

Univariate analysis showed that fluid balance is an important covariate. Based on the scatterplot distribution, a significant difference in mortality was determined between groups stratified with a balance of 1000 ml. There were associations in the multivariate analysis between poor outcomes and sex, PO2/FiO2, serum creatinine, FiO2, platelets, respiratory rate, SPO2, temperature, and total fluid volume (1000 ml). Among these variables, total fluid balance (1000 ml) had an OR of 1.98 (CI: 1.41-2.77, p < 0.001). Therefore, the model was built with these nine factors using XGBoost. Cross validation was used to verify generalizability. This model performed better than the SOFA and APACHE II models. The result was well verified in the verification cohort. A causal forest model suggested that patients with hypoxemia may suffer from positive fluid balance.

Sepsis fluid resuscitation in the ICU should be a targeted and goal-oriented treatment. A new prognostic prediction model was constructed and indicated that a 6-hour positive fluid balance after ICU initial admission is a risk factor for poor outcomes in sepsis patients. A 6-hour fluid balance above 1000 ml should be performed with caution.

Hospitals with higher septic shock case volume demonstrated lower hospital mortality. We conducted this study to investigate whether this phenomenon was only caused by the increase in the number of admissions or the need to improve the medical care capacity in septic shock at the same time.

Seven-hundred and eighty-seven hospitals from China collected in a survey from January 1, 2021 to December 31, 2021. Medical care capacity for septic shock was explored by patients with septic shock in intensive care units (ICU) divided into beds, intensivists, and nurses respectively.

The proportion of ICU patients with septic shock was negatively associated with the patient mortality of septic shock (Estimate [95%CI], -0.2532 [-0.5038, -0.0026]) (p-value 0.048). The ratios of patients with septic shock to beds, intensivists, and nurses were negatively associated with mortality of septic shock (Estimate [95%CI], -0.370 [-0.591, -0.150], -0.136 [-0.241, -0.031], and -0.774 [-1.158, -0.389]) (p-value 0.001, 0.011 and < 0.001). Severe pneumonia, the most common infection that caused a septic shock, correlated positively with its mortality (Estimate [95%CI], 0.1002 [0.0617, 0.1387]) (p-value < 0.001).

Hospitals with higher medical care capacity for septic shock were associated with lower hospital mortality.

Sepsis is a critical medical condition associated with high mortality for patients. Current pharmacological strategies for sepsis management or prevention had not achieved satisfactory results. The omega-3 fatty acids, with anti-inflammatory benefits, are considered to be promising agents for sepsis management/prevention. The aim of this network meta-analysis (NMA) is to compare the efficacy of various dosages and formulations of fish oil supplements for sepsis management and sepsis prevention. The current NMA consisted of two parts: (1) sepsis management and (2) sepsis prevention. The PubMed, ClinicalKey, Embase, ProQuest, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of February 22nd, 2024 for relevant randomized controlled trials (RCTs). RCTs were eligible for inclusion if they enrolled participants with a diagnosis of sepsis or who with high risk for sepsis. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed are (1) mortality rate in sepsis treatment or (2) incidence of sepsis in sepsis prevention. Our NMA, based on 28 RCTs and 1718 participants (mean age=51.6 years, mean female proportion=35.6 %), showed that (1) high dose parenteral fish oil supplement yield the lowest mortality rate in sepsis management in adult patients, and (2) high dose enteral fish oil supplement yield the lowest incidence of sepsis in pediatric patients. This study provides compelling evidence that high-dose fish oil supplements provide beneficial effects for both sepsis management and sepsis prevention. Our findings provide a preliminary rationale for future large-scale RCTs to investigate the role of fish oil supplementation in sepsis management or prevention.

Septic shock remains a potentially life-threatening complication among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. There is a paucity of information on the clinical characteristics, outcome and prognostic factors of septic shock patients after allo-HSCT. We aimed to describe the clinical characteristics of septic shock after allo-HSCT and its associated health outcomes and to evaluate the role of patient demographics, transplantation-related laboratory and clinical variables associated with the short-term mortality of septic shock after allo-HSCT. We retrospectively studied 242 septic shock patients from 6105 consecutive patients allografted between 2007 and 2021. We assessed 29 risk factors as candidate predictors and used multivariable logistic regression to establish clinical model. The primary outcome was 28-day mortality. The median age of the subjects was 34 (IQR 24 to 45) years. A total of 148 patients (61.2%) had positive blood cultures. Gram-negative bacilli accounted for 61.5% of the positive isolates, gram-positive cocci accounted for 12.2%, and fungi accounted for 6.1%. Coinfections were found in 30 (20.3%) patients. Escherichia coli was the dominant isolated pathogen (31.1%), followed by Pseudomonas spp. (12.8%) and Klebsiella pneumoniae (10.1%). With a median follow-up of 34 (IQR: 2 to 528) days, a total of 142 (58.7%) patients died, of whom 118 (48.8%) died within the first 28 days after septic shock diagnosis, 131 (54.1%) died within 90 days, and 141 (58.3%) died within 1 year. A large majority of deaths (83.1% [118/142]) occurred within 28 days of septic shock diagnosis. Finally, 6 independent predictive variables of 28-day mortality were identified by multivariable logistic regression: time of septic shock, albumin, bilirubin, PaO2/FiO2, lactate, and sepsis-induced coagulopathy. Patients with late onset shock had higher 28-day mortality rates (64.6% versus 25.5%, P < .001) and more ICU admission (32.6% versus 7.1%, P < .001) than those with early onset shock. We highlight the poor survival outcomes in patients who develop septic shock, emphasizing the need for increasing awareness regarding septic shock after allo-HSCT. The information from the current study may help to assist clinicians in identifying high-risk patients.