To evaluate early central venous-to-Pa co2 difference (∆P co2 ) and its correlation with later lactate concentration in pediatric patients with shock. Prospective observational study. Two medical-surgical PICUs in a tertiary-care university hospital. Children younger than 18 years old with septic or cardiogenic shock admitted to the PICUs (March 2021 to December 2022). None. Demographic, clinical, and outcome data were collected from medical records. Arterial and central venous blood samples were collected simultaneously at PICU admission and 6, 24, and 48 hours after admission to determine ∆P co2 , arterial lactate concentration, lactate clearance, and central venous oxygen-hemoglobin saturation (Scv o2 ). Left ventricle ejection fraction (LVEF) was estimated by echocardiography. Fifty-four patients 1.1 to 203.1 months old (median, 25.2 mo old) were included: (43/54 [79.6%] had septic shock and 11/54 [20.4%] had cardiogenic shock). Patients were divided into two groups according to ∆P co2 at 6 hours (24 ≤ 6 mm Hg and 30 > 6 mm Hg). The group with ∆P co2 greater than 6 mm Hg, compared with the group less than or equal to 6 mm Hg, had a higher Vasoactive-Inotropic Score and Pediatric Logistic Organ Dysfunction score, and there was a higher proportion of patients with low LVEF, elevated lactate concentrations, reduced lactate clearance, and Scv o2 less than 70%. ∆P co2 positively correlated with lactate concentrations and negatively correlated with lactate clearance and Scv o2 . The ∆P co2 cutoff of 7.5 mm Hg at 6 hours had sensitivity of 0.70, specificity of 0.76, positive predictive value of 0.87, and negative predictive value of 0.54 for predicting lactate clearance less than 10% at 24 hours (area under the receiver operating characteristic curve, 0.81 [95% CI, 0.69-0.91]). There were no differences in clinical outcomes between the groups. In pediatric shock, ∆P co2 measured 6 hours after presentation is correlated with subsequent lactate clearance at 24 hours and may serve as an early resuscitation and severity stratification metric.

Background: Sepsis management in elderly populations presents unique challenges due to age-related physiological changes and comorbidities. Current guidelines remain conflicted regarding optimal antibiotic timing. We conducted a retrospective, multicenter study to evaluate the association between antibiotic administration timing and short-term and long-term outcomes in elderly sepsis patients. Methods: This retrospective cohort study analyzed data from the MIMIC-IV (v3.1) database. Patients were categorized into the early group (antibiotics initiated within 1 h) and the late group (antibiotics initiated >1 h after diagnosis). Further analyses were stratified by shock status (septic shock vs non-septic shock) and pathogen type (Gram-positive vs Gram-negative bacteria). Multivariable Cox regression assessed associations between antibiotic administration timing and 28-/180-/365-day hospital mortality. Restricted cubic spline models evaluated dose-response relationships. The primary outcome was 28-day hospital mortality. Secondary outcomes included 180-day and 365-day mortality rates, along with the incidence of continuous renal replacement therapy (CRRT) and mechanical ventilation requirements. Results: A total of 12,425 patients met the inclusion criteria from the MIMIC-IV database. The multivariable-adjusted analysis demonstrated that delayed antibiotics administration was significantly associated with a 35% increased risk of 28-day all-cause hospital mortality (HR = 1.35, 95% CI 1.22-1.52; P < 0.001), a 43% elevated 180-day hospital mortality risk (HR = 1.43, 95% CI 1.30-1.56; P < 0.001), and a 45% higher 365-day mortality risk (HR = 1.45, 95% CI 1.33-1.56; P < 0.001). Stratified analyses revealed mortality benefits persisted in non-shock patients (28-day HR = 1.31, P < 0.001) and Gram-positive infections (28-day HR = 1.63, P < 0.001), whereas no significant associations emerged in septic shock (28-day HR = 0.82, 95%CI 0.65-1.03; P = 0.081) or Gram-negative infections (HR = 1.04, 95%CI 0.87-1.24; P = 0.692). A linear relationship was observed between antibiotic delay and mortality (Nonlinear P = 0.88). Conclusions: Early antibiotic administration improves survival in elderly sepsis patients, particularly non-shock cases and Gram-positive infections. These insights advocate the importance of individualized selection based on patients' clinical context in critical care practice.

A dysregulated host response to infection results in sepsis, where the mortality rate is high. A crucial component of managing sepsis is early detection and diagnosis. Advanced Haematology analyzers use volume, conductivity, and scatter (VCS) parameters to measure monocyte distribution width (MDW). An abnormal monocyte distribution width (MDW) greater than 20 U is considered a sign of sepsis. This study was done to utilize the potential of MDW as an early sepsis marker in ICU patients. Venous blood samples were collected from seventy-four patients suspected of having sepsis during a two-year prospective observational study. Sepsis cases were identified using the Systemic Inflammatory Response Syndrome (SIRS) criteria. Patients who received blood transfusions were excluded from this study. The DxH900 Haematology Analyzer (Beckman Coulter Inc., Miami, FL) was used to measure the MDW value. Procalcitonin (PCT), C-reactive protein (CRP), and total leucocyte count (TLC) were among the other conventional biomarkers of sepsis that were assessed. Seventy-four patients met the criteria for sepsis, of which twenty-three had septic shock. MDW was highest for patients in septic shock (P-value = 0.018). We have observed that as TLC, CRP, and PCT levels increased, so did MDW. As the SIRS score rose, it was discovered that the mean MDW value increased. In advanced Haematology analyzers, MDW, a new hematological parameter, is computed along with the complete blood count. When combined with other sepsis biomarkers, MDW is anticipated to be a helpful indicator for early sepsis screening in intensive care unit patients.

Sepsis is a recognized risk factor for upper gastrointestinal bleeding, yet sepsis-specific randomized evidence informing stress ulcer prophylaxis remains limited. This protocol describesthe rationale, methods, and statistical analysis plan for a post hoc subgroup analysis evaluating pantoprazole versus placebo in invasively ventilated critically ill adults with septic shock enrolled in the REVISE trial (NCT03374800). This study will be a post hoc extended subgroup analysis of the international, blinded, randomized REVISE trial, which enrolled 4821 mechanically ventilated adults in 68 ICUs across 8 countries. Patients were randomized to intravenous pantoprazole 40 mg once daily or placebo during invasive mechanical ventilation. Septic shock will be defined as receipt of vasopressors or inotropes at baseline together with an admitting diagnosis of infection according to APACHE III diagnostic categories. The primary efficacy outcome will be clinically important upper gastrointestinal bleeding in the ICU within 90 days after randomization, and the primary safety outcome will be all-cause mortality within 90 days. Additional trial outcomes will include patient-important upper gastrointestinal bleeding, ventilator-associated pneumonia, Clostridioides difficile infection during hospitalization, new renal replacement therapy, mortality in the ICU and hospital, and duration of ICU and hospital stay. Analyses will be adjusted for prehospital acid suppression; the mortality analyses will be additionally adjusted for APACHE II score. This protocol and statistical analysis plan describes an evaluation of the efficacy and safety of pantoprazole in patients with septic shock within a large randomized trial dataset. Trial Registration: ClinicalTrials.gov identifier: NCT03374800.

Individual differences exist in the recovery of muscle strength in critically ill patients with intensive care unit (ICU)-acquired weakness, but the characteristics of patients who do not recover muscle strength are unclear. To elucidate the factors associated with the nonrecovery of muscle strength in patients with ICU-acquired weakness. This prospective cohort study involved critically ill patients with ICU-acquired weakness. The patients' outcomes were categorized as recovery (Medical Research Council Sum Score [MRC-SS] ≥48 until hospital discharge or the time of stroke, death, or ICU readmission) or nonrecovery (MRC-SS <48). Separate logistic regression analyses adjusted for age and sex were performed for each candidate factor to identify factors associated with nonrecovery of muscle strength. A total of 111 patients were included in the analysis. Thirty patients were classified as having nonrecovery. Analysis using a logistic regression model showed that septic shock, duration of deep sedation, corticosteroid use, total amount of corticosteroids used, duration of mechanical ventilation, duration of renal replacement therapy, day of first out-of-bed mobilization, initial evaluation of MRC-SS, and length of ICU stay were age- and sex-adjusted predictors of nonrecovery of muscle strength. Patients with ICU-acquired weakness with the predictors identified in this study may not recover muscle strength. Future multicenter interventional studies should assess not only the timing of rehabilitation but also its intensity and the muscle groups specifically targeted.

Treatment-related adverse events of CD3-based T cell-engaging bispecific antibodies in patients with cancer: a meta-analysis of clinical trials.

Pulmonary microcirculatory dysfunction is a hallmark of sepsis, contributing to hypoxemia, pulmonary edema, and multiple organ failure. Anisodamine hydrobromide (ADM), a natural alkaloid with anti-inflammatory and endothelial-protective properties, has been used clinically in China for septic shock. However, its effects on pulmonary microcirculatory dysfunction in septic shock remain unclear. A rat model of sepsis was established via cecal ligation and puncture (CLP). Rats were treated with low, medium, or high doses of ADM. Seven-day survival rates and arterial blood gas parameters were monitored. Pulmonary microvascular leakage was evaluated using Evans blue extravasation and FITC-dextran imaging. Histological analysis, immunofluorescence, and Western blotting were performed to assess leukocyte adhesion, inflammatory cell infiltration, endothelial junction proteins, basement membrane proteins, and matrix metalloproteinases. ADM treatment significantly improved 7-day survival and restored arterial partial pressure of oxygen (PaO2), oxygen saturation (SaO2), and pH in CLP rats. High-dose ADM markedly reduced Evans blue and FITC-dextran leakage, attenuated pulmonary edema, and preserved alveolar architecture. ADM inhibited leukocyte adhesion in pulmonary microvessels and decreased infiltration of MPO- and CD68-positive inflammatory cells. Mechanistically, ADM suppressed CLP-induced Caveolin-1 upregulation, restored the expression of VE-Cadherin, Occludin, and Claudin-5, and prevented degradation of Collagen IV and Laminin. Additionally, ADM significantly downregulated MMP-9 expression, while MMP-2 levels remained unchanged, suggesting a role in limiting junctional and basement membrane degradation. ADM protects against CLP-induced pulmonary microcirculation dysfunction in rats by attenuating inflammatory cell infiltration, preserving pulmonary endothelial junctions, and maintaining basement membrane integrity. These results provide mechanistic insight into ADM's therapeutic potential in sepsis-induced pulmonary microcirculation dysfunction and support its use for sepsis in clinic.

Capnocytophaga canimorsus is a fastidious, capnophilic Gram-negative rod transmitted through exposure to the oral secretions of domesticated dogs and cats and may cause severe infection in immunocompromised hosts. Bacterial peritonitis due to C. canimorsus is rare and has been reported primarily in patients receiving peritoneal dialysis. We describe a 66-year-old man status post simultaneous liver and kidney transplantation who presented with septic shock, neutropenia, acute kidney injury, and worsening ascites. Peritoneal fluid analysis demonstrated neutrophilic ascites consistent with bacterial peritonitis, although cultures were negative. Blood cultures and broad-range bacterial polymerase chain reaction using 16S rRNA gene sequencing identified C. canimorsus, confirming the diagnosis. The patient reported close contact with pet dogs and improved with targeted beta-lactam therapy. This represents the first reported case of C. canimorsus peritonitis in a solid organ transplant recipient and highlights the diagnostic value of molecular testing in culture-negative peritonitis.

Acute effects of norepinephrine infusion on electrocardiographic parameters: A prospective study focusing on the frontal QRS-T angle.

Sepsis is a leading cause of preventable death in low-resource settings, where delays in recognition and emergency department (ED) treatment are common. Limited access to training also contributes to poor outcomes. We hypothesized that a contextualized telesimulation and debriefing program would be associated with better sepsis-related outcomes and time-critical care processes in children presenting to our center in Kumasi, Ghana. We also determined the program's acceptability and feasibility in our clinical providers. We conducted a 12-month mixed-method quasi-experimental (before vs. after implementation) study at Komfo Anokye Teaching Hospital, 2023-2024. Pediatric ED providers completed 30-minute, low-bandwidth telesimulation sessions using culturally-adapted real patient videos, filmed in the local Ghanaian hospital. Clinical outcomes and care processes were evaluated pre- and post-intervention. Trained observers recorded time-critical interventions: shock recognition, oxygen use, IV access, fluid bolus, reassessment, blood cultures, and antibiotics. Acceptability and feasibility were assessed using validated surveys. Tertiary academic hospital with 1200 beds, including 15 pediatric ED beds and 4 PICU beds. ED healthcare providers as well as clinical data from patients 2 months to 14 years old, screened at triage for suspected sepsis or septic shock. None. Post- vs pre-implementation care periods had mortality of 7 of 67 (10%) vs. 25 of 70 (36%), which represents an associated decrease in odds ratio (OR) of death 0.2 (95% CI, 0.1-0.5; p = 0.001). The post- vs pre-implementation changes in care characteristics, included: greater odds of supplemental oxygen use (OR 2.4 [95% CI, 1.0-5.7] p = 0.044) and IV placement (OR 3.8 [95% CI, 1.3-13.1] p = 0.012). Also, among trainees, 44/45 agreed that the program was acceptable and feasible. In our 2023-2024 pre- vs. post-implementation study, we found that contextualized telesimulation and debriefing were associated with lower odds of mortality, improved characteristics of care, and were acceptable and feasible to the healthcare team.

Vasopressor Timing and Mortality Impact in Septic Shock: July 2026 Annals of Emergency Medicine Journal Club.

This literature review examines the importance of Evidence-Based Practice (EBP) in nursing, with a focus on its application in Intensive Care Units (ICUs). EBP, through the synthesis of qualitative and quantitative data, promotes evidence-based decision-making, improving care quality, reducing mortality, and limiting complications. The methodology involved a search of the MEDLINE, ELSEVIER, and SCOPUS databases for studies published from 2000 onwards. The findings highlighted key interventions, such as infection prevention, septic shock management, pressure ulcer prevention, and end-of-life care. Additionally, the use of telemedicine and artificial intelligence fosters the integration of EBP into nursing practice. Despite advancements, the review highlights challenges such as lack of time, insufficient training, and limited administrative support. Strategies are proposed, including continuous education, technological support, and strengthening clinical practice through information systems. The findings indicate that the full integration of EBP can lead to significant improvements in care quality and clinical outcomes in ICUs, establishing it as a vital tool for delivering high-level nursing care.

Severe sepsis and septic shock frequently require escalating vasoactive support, but the prognostic utility of vasoactive-inotropic score (VIS) trajectories during polymyxin B hemoperfusion (PMX-HP) in Asian ICUs remains unclear. We conducted a retrospective single-center cohort study in a tertiary medical ICU in Taiwan, enrolling consecutive adults with severe sepsis or septic shock who received PMX-HP between July 2013 and December 2019. VIS was calculated before PMX-HP (VIS1), immediately after PMX-HP (VIS2), and approximately 24h post-treatment (VIS3); the primary outcome was 28-day all-cause mortality. In 64 patients, median VIS decreased from 28.8 (IQR 13.0-47.6) at VIS1 to 18.1 (IQR 7.8-45.0) at VIS2 and was 16.9 (IQR 1.3-45.1) at VIS3 among patients with available VIS3 data. VIS1, VIS2, and VIS3 were higher in non-survivors than survivors. A mixed-effects model using log(VIS + 1) confirmed significant effects of time, survival status, and their interaction. In an exploratory time-dependent Cox model, higher time-updated log(VIS + 1) was associated with 28-day mortality. The immediate VIS change showed limited discrimination for 28-day mortality (AUC 0.57, 95% CI 0.43-0.72), whereas VIS3 demonstrated better discrimination (AUC 0.78, 95% CI 0.66-0.91). Adding VIS3 to APACHE II improved discrimination compared with APACHE II alone (AUC 0.81 vs. 0.63; Delta AUC + 0.18; p = 0.020). Kaplan-Meier analysis using the ROC-derived VIS3 cut-off of 14.56 showed significantly worse 28-day survival when VIS3 remained above this threshold. Late post-treatment VIS monitoring may support bedside risk stratification in severe sepsis and septic shock undergoing PMX-HP; multicenter validation is warranted.Clinical trial number Not applicable.

Early pathogen detection is crucial in sepsis. We hypothesized that detection of microbial circulating cell-free DNA by metagenomic next-generation sequencing (mNGS) improves clinical outcomes and health-related quality of life without increasing healthcare costs. This randomized, controlled, interventional, open-label, multicenter trial was conducted in 24 intensive care units across Germany. The intervention group (n = 200) received mNGS diagnostics in addition to standard-of-care microbiology, compared with standard-of-care microbiology alone (control group; n = 189). The primary endpoint was the Desirability of Outcome Ranking/Response Adjusted for Duration of Antibiotic Risk (DOOR/RADAR) score. The DOOR/RADAR score was not significantly improved at 28days after sepsis onset (intervention group: 3.21 ± 1.54; control group: 3.49 ± 1.51; 95% CI - 0.58 to 0.03). However, other secondary endpoints were improved, including a reduced duration of mechanical ventilation (intervention group: 6.6 ± 9.4days; control group: 9.3 ± 10.6days; 95% CI - 5.03 to - 0.34) and faster shock resolution (intervention group: 6.9 ± 7.4days; control group: 8.8 ± 8.5days; 95% CI - 3.75 to - 0.04). Health-related quality of life at 90days (EQ-5D-5L) was improved in the intervention group (0.312 ± 0.386) compared with the control group (0.208 ± 0.373; p = 0.047). In the subgroup with available claims data (33.2% of participating patients), healthcare costs over 180days did not differ. The DOOR/RADAR score as primary endpoint was not significantly improved by mNGS. Exploratory secondary analyses revealed improvements in secondary endpoints. (Funding: German Innovation Fund; ClinicalTrials.gov number, NCT04571801, registration: 25.8.2020).

Norepinephrine attenuates acute lung injury by protecting mitochondria via the β2-AR-AKAP1 axis and inhibiting alveolar epithelial pyroptosis.

Iatrogenic oesophageal perforation (IOP) is a rare but potentially fatal complication of orogastric (OG) or nasogastric tube insertion in preterm neonates, with mortality rates up to 30%. We describe the case of a female neonate born at 31 + 5 weeks of gestation (birth weight 1.8 kg) who required extensive resuscitation and OG tube insertion after admission to the neonatal intensive care unit. Admission chest radiograph showed right-sided pneumothorax with OG tube aberrantly positioned in the right hemithorax which was missed initially. Following intercostal drain insertion and commencement of enteral feeds, milky pleural drainage was observed. Normal pleural triglyceride levels excluded chylothorax, prompting radiographic re-evaluation and paediatric surgical review, leading to diagnosis of IOP. Despite conservative management, the infant developed septic shock with sclerema and died on the 4th day of life. This case emphasises careful radiographic confirmation of tube placement in preterm neonates and the diagnostic significance of milky pleural drainage following feeds.

To quantify the heterogeneity of treatment effects of higher versus standard MAP targets on 28-day mortality, to identify distinct clinical phenotypes that respond differentially to MAP targets, and to derive simple bedside decision rules to guide individualised haemodynamic management. Current guidelines recommend a uniform mean arterial pressure (MAP) target of ≥65 mmHg for septic shock. However, trials like SEPSISPAM found no mortality benefit from higher targets in hypertensive patients. We hypothesised that this null finding results from the masking of heterogeneous treatment effects (HTEs) among phenotypically distinct individuals. We conducted a retrospective cohort study of 7665 hypertensive patients with septic shock from the Medical Information Mart for Intensive Care IV database (version 3.1). The primary exposure was time-weighted average MAP (TWA-MAP) during the first 24 h, dichotomised into high target (>75 mmHg) versus standard target (65-75 mmHg). The primary outcome was 28-day mortality. Individual treatment effects (ITEs) were estimated using a T-Learner causal machine learning framework with gradient boosting. Patients were stratified by ITE quartiles, and a Classification and Regression Tree (CART) was used to derive bedside clinical rules. We observed marked HTE (ITE range: -0.54 to +0.86). In the Strong Benefit group (Decompensated Phenotype) - characterised by tachycardia, hyperlactatemia and renal dysfunction - the high MAP target dramatically reduced 28-day mortality from 62.6% to 22.9% (absolute risk reduction = 39.7%, P < 0.001). Conversely, in the Harm group (Frail Phenotype) - characterised by older age and lower heart rate - the high target increased mortality from 14.7% to 33.9% (ARR = -19.2%, P < 0.001). The CART model identified heart rate >105 bpm and creatinine >1.65 mg/dL as simple bedside criteria to identify patients likely to benefit from higher targets. The impact of higher MAP targets in hypertensive septic shock exhibits a distinct crossover pattern: life-saving in decompensated patients but harmful in frail patients. This HTE explains the null results of previous landmark trials. Utilising simple parameters like heart rate and creatinine can guide a shift from 'one-size-fits-all' targets towards precision haemodynamic management.

Sepsis is characterized by adysregulated host response to infection and remains associated with substantial mortality. Extracorporeal blood purification strategies are explored as adjunctive approaches to modulate host-response dysregulation. Practice-oriented overview of current extracorporeal immunomodulatory strategies in sepsis and septic shock and asummary of available evidence and guideline position. Narrative review focusing on randomized trials, meta-analyses, guidelines, and ongoing study programs addressing nonselective hemoadsorption, selective endotoxin removal, and therapeutic plasma exchange. Evidence for nonselective hemoadsorption remains conflicting; recent higher-quality studies and guidelines do not show aproven clinical benefit and raise potential safety concerns. Selective endotoxin adsorption is biologically plausible and may be relevant in endotoxin-positive subgroups. Therapeutic plasma exchange is supported by mechanistic rationale, small randomized studies, and meta-analyses; confirmation in adequately powered multicenter trials is pending. Extracorporeal immunomodulation should not be regarded as auniform intervention. Progress will depend on precise patient selection, biomarker-guided allocation, appropriate dosing, and structured implementation. Until robust outcome data are available, these therapies should be used cautiously and preferably in experienced centers or study frameworks.

The aim of our study was to compare the prevalence, etiology, and outcomes of sepsis and associated AKI in pre- and post-COVID-19 pandemic. We conducted a retrospective observational analysis in 144 patients with sepsis and AKI, in two periods of time, 2 years before and after COVID-19 pandemic, with 2 years' washout period. The comparative analysis between the two periods demonstrated more severe forms of sepsis with septic shock dominating in the post pandemic period (5 (10%) vs 23 (25%), p = 0.037). According AKI staging we found AKI stage 3 more frequently present after pandemic and more patients needed dialysis in the post COVID-19 pandemic (35 (70%) vs 79 (84%), p = 0.04; 31 (62%) vs 78 (54%), p = 0.02; 16 (32%) vs 51% (54%), p = 0.018), respectively. Patients in post COVID-19 era survived less longer (22.66 ± 11.32 vs 17.132 ± 12.66, p = 0.021) with almost doubled risk for mortality HR: 1.977; 95% CI (1.127 ± 3.469), p = 0.018. Regarding causative agents' there was similar distribution in both periods, but the multiple antibiotic resistance index (MAR) was significantly higher in the post COVID-19 period for Staphylococcus coagulase negative (0.48 vs 0.62, p = 0.001). Sepsis and associated AKI occurrence, morbidity and mortality are significantly higher in the post COVID-19 pandemic and the increased MAR of the germs can be one of the main reason for it.

Presepsin outperforms conventional biomarkers for Sepsis diagnosis and 30-day mortality prediction: A multicenter prospective study in a north African ICU cohort.