Effects on mortality of blood purification techniques in severe septic shock patients. An updated Bayesian network meta-analysis of randomized controlled trials.

Dysphagia is commonly associated with intensive care unit-acquired weakness (ICUAW), with oropharyngeal muscular weakness considered a major precipitating factor. Unfortunately, evidence for effective rehabilitation of dysphagia associated with ICUAW is lacking. The aim of this study was to examine the feasibility, safety, and effectiveness of a strength-based dysphagia treatment protocol for patients with dysphagia associated with ICUAW. A prospective pilot cohort study was conducted on all critically ill patients admitted to an Australian tertiary referral intensive care unit (ICU) over a 3-year period, diagnosed with dysphagia and ICUAW. A strength-based dysphagia treatment protocol was implemented incorporating expiratory muscle strength training and swallowing exercises to target the tongue base, pharyngeal, suprahyoid, and respiratory muscles. A regime of five sets of five repetitions, conducted 5 days per week, was employed. Treatment commenced in the ICU, continuing until swallowing recovery or swallowing function plateaued. Key swallowing and respiratory outcomes were collected weekly: clinical swallow examination (Functional Oral Intake Scale [FOIS]: 1-7), flexible endoscopic evaluation of swallowing (New Zealand Secretion Scale: 0-7, Penetration-Aspiration Scale: 1-8] Yale Pharyngeal Residue Scale [Yale]: 1-5), peak expiratory flow (PEF), and maximum expiratory pressure (MEP). Thirteen participants (11 male, median age = 52 years) were recruited. Medical diagnoses included severe burn injury, influenza-A, necrotising pancreatitis, sepsis, and COVID-19 infection. Median mechanical ventilation was of 19 days (interquartile range [IQR] = 16-36 days), ICU length of stay was of 34 days (IQR = 21-43 days), and hospital length of stay was of 71 days (IQR = 43-86 days). Four required tracheostomy (median: 18 days, IQR = 13-24 days). All participants exhibited profound dysphagia (FOIS = 1-3, New Zealand Secretion Scale = 3-7, Penetration-Aspiration Scale = 3-8, Yale Pharyngeal Residue Scale = 2-5) and respiratory impairment at baseline (MEP = 21-114 cmH2O, PEF = 80-310 L/min). All completed the treatment protocol and achieved premorbid diet and fluids (FOIS = 7) and functional respiratory status (MEP = 62-178 cmH2O, PEF = 260-520 L/min) by hospital discharge. No adverse events were recorded. Pilot study findings suggest that a strength-based dysphagia treatment protocol for patients with ICUAW and dysphagia is safe and feasible with promising outcomes indicating that it may support dysphagia recovery in this challenging population.

New world screwworm: A focused review for the emergency medicine clinician.

Sepsis and septic shock remain major causes of morbidity and mortality worldwide, and management is largely based on source control, antimicrobial therapy, and supportive care. Despite limited high-quality evidence, adjunctive therapies targeting the dysregulated host response involving immune dysfunction, coagulopathy, and endothelial injury, steroids, vasopressors, and adjunctive therapies are frequently used in clinical practice. This survey aimed to describe real-world patterns of sepsis therapy across Europe. We conducted an open, web-based, multinational survey endorsed by the European Society of Intensive Care Medicine (ESICM) and the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). The survey was distributed through professional mailing lists, newsletters, and national society networks. A structured 30-item questionnaire collected information on respondent demographics, ICU characteristics, availability of adjunctive therapies, clinical indications, triggers for initiation, and duration of treatment. Participation was voluntary and anonymous. A total of 442 physicians completed the survey. Data were analyzed descriptively and are presented as proportions and frequencies. More than 80% of respondents reported use of at least one adjunctive therapy for septic shock within the previous year. Corticosteroids were used by over 90% of clinicians, predominantly hydrocortisone for septic shock. Considerable variability was observed regarding indications, timing of initiation, and duration of therapy. Extracorporeal blood purification techniques were used by approximately 75% of respondents, most frequently hemoadsorption in patients with refractory shock; high cost and limited availability were the main barriers to broader implementation. Intravenous immunoglobulins were used by approximately one-third of clinicians, often guided by measured immunoglobulin levels or perceived immune dysfunction. Additional vasoactive and inotropic agents, including levosimendan, methylene blue, and beta-blockers, were employed in selected cases. In contrast, specific immunomodulatory therapies such as interleukin (IL)-1receptor antibodies were rarely used. Across all adjunctive strategies, marked heterogeneity in practice patterns was evident. Adjunctive therapies are widely used in European ICUs, particularly in patients with severe or refractory sepsis, despite limited supporting evidence. The substantial variability in practice highlights ongoing clinical uncertainty and underscores the need for well-designed randomized trials to inform evidence-based and individualized treatment strategies.

Background: Vitamin D plays an important role in immune regulation, and vitamin D deficiency has been increasingly associated with susceptibility to infection and adverse outcomes in critically ill patients. Numerous systematic reviews and meta-analyses have examined the relationship between vitamin D status, vitamin D receptor (VDR) gene polymorphisms, and sepsis; however, the evidence remains fragmented. Objective: The aim of this work was to synthesize high-level evidence on the association between vitamin D deficiency, VDR gene polymorphisms, vitamin D supplementation, and sepsis-related outcomes through a PRISMA 2020-compliant umbrella review. Methods: An umbrella review of systematic reviews and meta-analyses published between 2014 and 2025 was conducted using PubMed, PubMed Central, and journal archives. Eligible studies included adult, pediatric, and neonatal populations and evaluated sepsis incidence, mortality, disease severity, secondary outcomes, and genetic associations. Data were synthesized qualitatively due to overlap of primary studies and heterogeneity. Conceptual forest plots and funnel plots were used to summarize evidence direction and potential publication bias. Results: Nineteen systematic reviews and meta-analyses encompassing over 300 primary studies were included. Vitamin D deficiency was consistently associated with an increased risk of sepsis, higher mortality, and greater disease severity across adult and pediatric populations. Stronger associations were observed in children and neonates, including higher PRISM III scores, increased need for mechanical ventilation, and longer hospital stays. VDR gene polymorphisms were modestly but consistently associated with increased sepsis susceptibility. In contrast, vitamin D supplementation did not demonstrate a consistent reduction in sepsis risk or mortality. Conclusions: Vitamin D deficiency is a robust marker of sepsis risk, severity, and poor prognosis, whereas current evidence does not support vitamin D supplementation as an effective treatment for established sepsis.

Objective: To assess the short-term effect of oral zinc supplementation on mortality in preterm neonates with bacterial sepsis. Study Design: Randomized Controlled Trial. Setting: The Neonatal Unit of Sharif Medical City Hospital, Lahore. Period: December 20, 2021 to June 20, 2022. Methods: A total of 250 preterm neonates with gestational age between 28–36 weeks and diagnosed with sepsis were enrolled using non-probability consecutive sampling technique. They were randomly distributed into two groups. Group A received zinc supplementation orally (3 mg/kg twice daily), while Group B received distilled water as a placebo. Both groups received standard antibiotic treatment. Neonates were monitored in the NICU until discharge or death, and 7-day mortality was recorded. Chi-square test was applied to associate mortality rates. The p value of ≤ 0.05 was considered statistically significant. Results: The mean age of neonates in Group A was 41.19 ± 19.10 hours, while in Group B, it was slightly lower at 39.24 ± 19.63 hours. Group A had a significantly lower 7-day mortality rate of 9(7.2%) compared to Group B at 26(20.8%) (p = 0.002). No deaths occurred in the 6–18 hour age subgroup of Group A, while Group B had 8(6.4%) deaths (p = 0.005). Mortality was significantly lower in Group A among neonates with higher birth weights: 3(2.4%) vs. 12(9.6%), (p = 0.007) and gestational ages of 31–33 weeks: 5(4.0%) vs. 19(15.2%), (p < 0.001). Conclusion: Oral zinc supplementation significantly decreased short-term mortality in preterm neonates with sepsis. Zinc may serve as an effective adjunct therapy in managing neonatal sepsis.

Pharmacological elevation of lactate alleviates sepsis via histone lactylation-induced IL-10 production.

Sepsis triggers both excessive inflammation and immunosuppression, the latter partly characterized by CD4+ T-cell depletion. The mechanisms underlying this depletion, especially its interplay with cytokine storms driven by inflammatory factors such as interleukin (IL)-6, remain unclear. This study aimed to elucidate the molecular mechanisms contributing to CD4+ T-cell depletion in sepsis, focusing specifically on the IL-6/Janus kinases (JAKs)/signal transducer and activator of transcription 3 (STAT3) signaling axis and programmed cell death. Prospective cohort study. Adult ICUs at a university hospital. Adult sepsis and septic shock patients without any documented immune comorbidity. None. A prospective analysis enrolled 151 patients (93 sepsis, 58 septic shock) and 20 controls. Flow cytometry and enzyme-linked immunosorbent assay were used to assess immune cell populations and cytokine profiles, with multivariate analyses exploring their interrelationships. An additional 30 sepsis patients and ten controls were recruited to investigate mechanisms. Peripheral blood mononuclear cells (PBMCs) underwent RNA sequencing (RNA-seq). Isolated CD4+ T cells were stimulated with IL-6 in vitro, followed by treatment with specific inhibitors targeting pyroptosis, apoptosis, necroptosis, the JAKs/STAT3 pathway, or receptor-interacting protein kinase 1 (RIPK1). Western blotting, flow cytometry, immunofluorescence, Cell Counting Kit-8 assays, and interferon-gamma staining evaluated cell death pathways, PANoptosome (a complex mediating apoptosis, pyroptosis and necroptosis)-assembly, and function. Significant CD4+ T-cell loss occurred in both sepsis and septic shock groups, strongly correlating with elevated IL-6 levels. Sepsis PBMC RNA-seq revealed activated IL-6/JAKs/STAT3 signaling and upregulated apoptosis/pyroptosis/necroptosis genes. In vitro, IL-6 induced pyroptosis, apoptosis, and necroptosis (PANoptosis) in CD4+ T cells via IL-6/JAKs/STAT3-dependent RIPK1-PANoptosome assembly. Inhibiting JAKs/STAT3 or RIPK1 significantly reduced PANoptosis, partially restored CD4+ T-cell viability and functional capacity. PANoptosis has been observed to be a form of CD4+ T-cell death in sepsis patients. Evidence suggests that IL-6 may be associated with the exhaustion process, mechanistically involving the activation of the JAKs/STAT3 pathway. It is also hypothesized that this process might be linked to RIPK1-PANoptosome-mediated PANoptosis.

Objective. To evaluate the efficacy and safety of ulinastatin in patients with postoperative abdominal sepsis (AS) in intensive care units. Materials and methods. This randomized study included 60 patients with AS divided into two groups: the ulinastatin group (n = 30) received standard intensive therapy combined with intravenous ulinastatin (200,000 IU three times daily for 3 days, followed by 100,000 IU three times daily for 4 days); the control group (n = 30) received standard intensive therapy alone. Clinical outcomes, organ dysfunction (SOFA score, Glasgow Coma Scale), laboratory markers of inflammation (CRP, PCT, HLA-DR), and cytokine levels (TNF-α, IL-6) were assessed before and after therapy. The primary endpoint was 28-day mortality. Results. Baseline patient characteristics and laboratory parameters were comparable between the groups. The administration of ulinastatin significantly reduced 28-day mortality (10.0 % vs. 33.3 %; p 0.01) and the number of new organ dysfunction cases (10 vs. 26; p = 0.003). Patients in the ulinastatin group showed an increase in ventilator-free days (18.4±7.4 vs. 12.2±5.1; p = 0.035) and a reduced mean hospital stay (by 13.6 days; p 0.001). Patients in the ulinastatin group demonstrated a significant decrease in CRP, PCT, TNF-α and IL-6 levels, and an increase in HLA-DR levels (p 0.05). Multivariate analysis confirmed ulinastatin use as an independent factor for reducing the risk of death (OR=0.45; 95 % CI: 0.21–0.74; p = 0.018). Conclusions. The inclusion of ulinastatin in the comprehensive treatment of postoperative AS significantly suppresses the inflammatory response, improves clinical outcomes, and reduces 28-day mortality. These findings justify the use of ulinastatin in the management of this severe patient population and require confirmation in large randomized studies.

Abstract Pyoderma gangrenosum (PG), as a complication of aesthetic surgery, is an unpleasant experience for both the surgeon and the patient. It can have serious health consequences and cause both mental and physical suffering. In some cases, it may be accompanied by the development of a systemic inflammatory response, which can be life-threatening, and may even represent the first manifestation of an autoimmune, systemic, or oncological disease. We present the case of a patient in her mid-40 s with autoimmune hypothyroidism on substitution therapy. Following bilateral periareolar mastopexy with augmentation, the patient developed fever and bilateral wound complications on postoperative day 5, including redness, swelling, wound exudate, ulceration, and dehiscence at the surgical incision sites, with subsequent progression to sepsis-like systemic inflammatory reaction/ severe systemic inflammatory response. Rapid consideration of pyoderma gangrenosum as a potential diagnosis led to implant removal and initiation of corticosteroid therapy on day 8. The patient reported subjective improvement within 24 h following corticosteroid administration, with an early reduction in body temperature and overall clinical improvement. Thanks to early recognition (from symptom onset to initiation of corticosteroid therapy and implant removal), we were able to prevent further deterioration of the local findings and avoid progression to severe sepsis within 10 days. Corticosteroid therapy was continued for nine months, together with supportive wound care, until full recovery. Subsequent evaluations did not reveal any new autoimmune or oncological diseases in this patient. We present new protocols and an algorithm at our department for managing similar situations, as well as for preoperative risk stratification and postoperative monitoring in aesthetic breast surgery, incorporating multidisciplinary consultations and tailored immunosuppressive strategies to reduce the incidence of PG and improve patient outcomes.

Sepsis and septic shock stimulate a massive inflammatory response during which neutrophil extracellular traps (NETs) release citrullinated histone H3 (CitH3) into the circulation, leading to tissue damage, coagulopathy, and organ failure. This study aimed to assess serum levels of CitH3 in patients with septic and non-septic shock in intensive care units and to study their correlation to septic shock severity. The study was conducted at Ain Shams University Hospitals and included 72 adult participants: 24 with septic shock, 24 with non-septic shock, and 24 healthy controls. Serum CitH3and procalcitonin (PCT) levels were measured using ELISA, and blood cultures were performed for septic shock patients. Median CitH3 levels were 5.58 ng/mL in healthy controls, 44.38 ng/mL in non-septic shock, and 198.7 ng/mL in septic shock patients (p < 0.001). CitH3 strongly correlated with SOFA scores (Non-septic: r = 0.793; Septic: r = 0.786) and ICU stay in septic patients (r = 0.477, p = 0.019). ROC analysis showed CitH3 performed better than PCT in distinguishing septic from non-septic shock patients (AUC 0.946 vs 0.747, p = 0.012) and from controls (AUC 0.991 vs 0.853, p = 0.017). Direct comparison also showed that CitH3 had superior predictive performance for mechanical ventilation (p = 0.038). CitH3 could be considered a reliable biomarker of septic shock. It can be regarded as a valuable tool for predicting prognosis and severity of sepsis. CitH3 could be a promising candidate for routine integration into sepsis management protocols.

Association of Unplanned ICU Admission and Clinical Outcomes in Trauma Patients With Severe Sepsis.

Racial and Ethnic Disparities Persist in Outcomes After the 2015 Severe Sepsis and Septic Shock Early Management (SEP-1) Bundle.

Pronostic factors for survival in candidemia among onco-hematology patients: a single-center retrospective study during 10 years.

Orientin alleviates severe inflammation via regulating macrophage glycolysis and immune function in sepsis.

Improving Antibiotic Administration Time in At-Risk Pediatric Populations: A Quality Improvement Project.

A novel biomimetic and redox-responsive hybrid lipid polymer nanoparticle for targeting sepsis microenvironment and modulating inflammation.

Septic cardiomyopathy (SCM) is a common and life-threatening complication of severe sepsis, with high mortality due to unclear underlying mechanisms. CXCL4, a key pro-inflammatory factor, is implicated in various heart diseases, while ferroptosis (iron and lipid hydrogen peroxide-dependent regulated cell death) plays a crucial role in SCM progression. However, the specific crosstalk between CXCL4, ferroptosis, and SCM remains unelucidated. BALB/c mice were randomly divided into six groups (Control, LPS, LPS + Sodium Cromoglycate (CS), LPS + Ferrostatin-1 (Fer-1), LPS + Pifithrin-α (PFT-α), LPS + Niclosamide) to establish the SCM model via intraperitoneal LPS injection. In vivo experiments included histopathological examination (H&E, toluidine blue staining), survival analysis, ELISA, Western blot, immunofluorescence, immunohistochemistry, TUNEL staining, and detection of myocardial markers (CK-MB, AST, LDH) and oxidative stress indicators (SOD, MDA, iron content). In vitro, RAW264.7 macrophages were treated with CXCL4 alone or combined with inhibitors (Fer-1, PFT-α, Niclosamide), followed by CCK-8 assay, ROS detection, qRT-PCR, Western blot, and phagocytosis microbead assay. In vivo, SCM mice exhibited significantly elevated CXCL4 levels in serum and heart tissue, accompanied by mast cell activation and degranulation. Inhibiting mast cell activation (with CS) reduced CXCL4 production, alleviated cardiac inflammation and ferroptosis (increased SLC7A11/GPX4 expression, decreased 4-HNE), and improved survival. TUNEL staining revealed predominant macrophage death in SCM hearts. In vitro, CXCL4 induced macrophage ferroptosis (downregulated SLC7A11/GPX4) and impaired phagocytic function (reduced CD36/MERTK expression), which was reversed by Fer-1. Mechanistically, CXCL4 activated STAT3 phosphorylation, regulating downstream P53; inhibiting STAT3 (Niclosamide) or P53 (PFT-α) alleviated macrophage ferroptosis, restored phagocytosis, and mitigated cardiac injury in SCM mice. Mast cell-derived CXCL4 induces macrophage ferroptosis via the STAT3/P53 signaling pathway, impairs macrophage phagocytic function, and exacerbates myocardial injury in SCM. Targeting mast cell activation, CXCL4 release, or the STAT3/P53-ferroptosis axis may serve as promising therapeutic strategies for SCM. Not applicable.

The Australian Commission on Safety and Quality in Healthcare developed a list of sixteen potentially preventable Hospital-Acquired Complications (HACs) and an algorithm using International Classification of Disease (ICD) codes to detect them. We evaluated this algorithm's performance for diagnosing hospital-onset bloodstream infections (HO-BSI). Administrative records were extracted for episodes of admitted patient care from July 2016 to June 2017 at five Australian principal referral hospitals. We applied the BSI HAC algorithm to each episode, then randomly selected 50 patients deemed positive and negative for HO-BSI at each site. Reviewers blinded to HAC status applied the reference surveillance definition for HO-BSI. The positive predictive value (PPV) and negative predictive value (NPV) for the BSI HAC were calculated. We explored changes to the HAC algorithm to improve these metrics. Overall, 352 917 episodes were included; median (IQR) age was 54 (33-71) years, 49.6 % were female, and 43.8 % were elective admissions. Of these, 2229 (0.6 %) had a HO-BSI according to the HAC algorithm. Among manually reviewed episodes, the PPV for the HAC algorithm was 0.28 (95 % CI, 0.23-0.34) and the NPV was 1.00 (95 % CI, 0.98-1.00). The codes 'Sepsis, unspecified' and 'bacterial sepsis of newborn, unspecified' were both common triggers for HO-BSI HACs (accounting for 35.8 % and 18.4 % of HO-BSIs, respectively) and had poor PPV (0.06 and 0.03, respectively). Removal of these codes from the algorithm increased PPV to 0.53 (0.45-0.62). The HAC algorithm had sub-optimal PPV for HO-BSI. This performance was improved by removing the 'unspecified sepsis' ICD codes.

Introduction: Critically ill patients with lung edema experience significant morbidity and mortality, with the gut-lung axis emerging as a potential therapeutic target. Probiotic interventions may modulate this bidirectional relationship, but evidence remains conflicting. This systematic review synthesizes evidence on probiotic effects on the gut-lung axis in critically ill adults with lung edema. Methods: A systematic review was conducted following PRISMA guidelines. We screened 200 sources from databases including PubMed, Scopus, and Web of Science (2000-2026). Included studies were randomized controlled trials, cohort studies, and meta-analyses examining probiotic or synbiotic interventions in critically ill adults (≥18 years) with lung edema/ARDS. Primary outcomes included ventilator-associated pneumonia (VAP), mechanical ventilation duration, and gut-lung axis mechanisms. Quality assessment used Cochrane Risk of Bias tools. Results: Forty-eight primary studies and 52 meta-analyses/systematic reviews were included (total N &gt;15,000 patients). Probiotics reduced VAP incidence (RR 0.52-0.75), with synbiotics showing greater efficacy (RR 0.61, 95% CI 0.47-0.80). Mechanical ventilation duration decreased by 1-2.5 days, and ICU length of stay by 1-2 days. Mortality reduction was inconsistent, though severe sepsis subgroups showed benefit (OR 0.38, 95% CI 0.16-0.93). Mechanistically, probiotics improved gut barrier function (reduced lactulose-mannitol ratio, enhanced tight junction proteins), modulated systemic inflammation (IL-6 reduction 140 pg/mL, CRP reduction 72.7%), increased short-chain fatty acid production, and reduced pathogenic colonization. The largest trial (PROSPECT, n=2,653) found no VAP reduction, highlighting context-dependent efficacy. Safety concerns included probiotic bacteremia (1.1% vs 0.1% in PROSPECT). Discussion: Probiotic efficacy is population-specific, with consistent benefits in trauma, surgical, and COVID-19 patients, but minimal effects in general mixed ICU populations receiving contemporary care. Synbiotics, higher doses (≥5×10⁹ CFU/day), and longer duration (≥14 days) optimize outcomes. Methodological quality explains discrepancies between early positive meta-analyses and recent negative trials. Conclusion: Probiotics modulate the gut-lung axis through multiple mechanisms, reducing VAP and ICU stay in selected populations. Routine use in unselected ICU patients is not supported, but targeted therapy in trauma and specific subgroups may be beneficial. Further research should optimize strain selection, dosing, and identify responsive phenotypes.