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Background: Senescent immune cells exhibit altered gene expression and resistance to apoptosis. The prevalence of these cells increases with age and emerging data implicate senescence-associated maladaptive signaling as a potential contributor to sepsis and septic shock. The senolytic drug fisetin promotes clearance of senescent cells and is hypothesized to mitigate septic responses to infection. Methods: We are conducting a multi-center, randomized, double-blinded, adaptive allocation phase 2 clinical trial to assess the efficacy of the senolytic drug fisetin in preventing clinical deterioration of elderly patients diagnosed with sepsis. We intend to enroll and randomize 220 elderly patients (age > 65) with the clinical diagnosis of sepsis to receive either fisetin as a single oral dose of 20 mg/kg, fisetin in two oral doses of 20 mg/kg each spaced 1 day apart, or placebo. The primary outcome will be changed in the composite of cardiovascular, respiratory, and renal sequential organ failure assessment scores at 7 days from enrollment. Secondary outcomes include quantification of senescent CD3 + cells at 7 days, and 28-day assessments of organ failure-free days, days in an intensive care unit, and all-cause mortality. Discussion: This multi-center, randomized, double-blinded trial will assess the efficacy of fisetin in preventing clinical deterioration in elderly patients with sepsis and measure the effects of this drug on the prevalence of senescent immune cells. We intend that the results of this phase 2 trial will inform the design of a larger phase 3 study. Trial registration: This trial is registered to ClinicalTrials.gov under identifier NCT05758246, first posted on March 7, 2023. [ABSTRACT FROM AUTHOR]

Introduction: Early administration of appropriate antibiotics has been shown to be among the most effective interventions to reduce mortality in septic patients. We evaluated the attainment of efficacy and safety targets at 24 h associated with the use of intensive beta‐lactam therapy in patients admitted to the intensive care unit for sepsis. Methods: This was a prospective study with patients who received beta‐lactams for sepsis or septic shock between February 2023 and September 2023. The antibiotic dose was unadjusted for renal function and administered by a loading dose followed by extended infusions, according to local practices. Blood samples were taken at the trough 24 h after the start of the beta‐lactam to obtain serum levels. These levels were compared to efficacy and innocuity thresholds found in the literature. Results: Among 36 included patients, all of them achieved serum concentrations above the minimum inhibitory concentration (MIC) for 100% of the therapeutic interval and 75% of them achieved serum concentrations above four times the MIC for 100% of the therapeutic interval. The predefined toxicity thresholds were reached by 8.3% of patients. Renal impairment was the factor most associated with the achievement of higher serum levels. Conclusion: Nonrenally adjusted doses of beta‐lactams administered by extended infusion showed good attainment of effective concentrations and few toxic concentrations in critically ill patients with sepsis or septic shock. Further studies are needed to better define the association between toxic concentrations and toxicity manifestations. [ABSTRACT FROM AUTHOR]

Sepsis-associated organ dysfunction plays a critical role in its high mortality, mainly in connection with mitochondrial dysfunction. Whether the inhibition of mitochondrial fission is beneficial to sepsis-related organ dysfunction and underlying mechanisms are unknown. Cecal ligation and puncture induced sepsis in rats and dynamic related protein 1 knockout mice, lipopolysaccharide-treated vascular smooth muscle cells and cardiomyocytes, were used to explore the effects of inhibition of mitochondrial fission and specific mechanisms. Our study showed that mitochondrial fission inhibitor Mdivi-1 could antagonize sepsisinduced organ dysfunction including heart, vascular smooth muscle, liver, kidney, and intestinal functions, and prolonged animal survival. The further study showed that mitochondrial functions such as mitochondrial membrane potential, adenosinetriphosphate contents, reactive oxygen species, superoxide dismutase and malonaldehyde were recovered after Mdivi-1 administration via improving mitochondrial morphology. And sepsis-induced inflammation and apoptosis in heart and vascular smooth muscle were alleviated through inhibition of mitochondrial fission and mitochondrial function improvement. The parameter trends in lipopolysaccharidestimulated cardiomyocytes and vascular smooth muscle cells were similar in vivo. Dynamic related protein 1 knockout preserved sepsis-induced organ dysfunction, and the animal survival was prolonged. Taken together, this finding provides a novel effective candidate therapy for severe sepsis/septic shock and other critical clinical diseases. [ABSTRACT FROM AUTHOR]

Background: Trauma and infection induce emergency granulopoiesis. Counts of immature granulocytes and transcriptional pathways of terminal granulocytic differentiation in blood are elevated in sepsis but correlate with disease severity. This limits their performance as sepsis biomarkers in critically ill patients. We hypothesized that activation of these pathways in sepsis is attributable to immature low-density (LD) rather than mature high-density (HD) granulocytes. Methods: We included patients with sepsis and systemic inflammatory response syndrome (SIRS) of comparable disease severity, and additionally septic shock, on intensive or intermediate care unit admission. Blood granulocyte isolation by CD15 MicroBeads was followed by density-gradient centrifugation. Flow cytometry was used to determine counts of developmental stages (precursors) and their relative abundancies in total, HD, and LD granulocytes. Five degranulation markers were quantified in plasma by multiplex immunoassays. A set of 135 genes mapping granulocyte differentiation was assayed by QuantiGene™ Plex. CEACAM4, PLAC8, and CD63 were analyzed by qRT-PCR. Nonparametric statistical tests were applied. Results: Precursor counts appeared higher in sepsis than SIRS but did not correlate with disease severity for early immature and mature granulocytes. Precursor subpopulations were enriched at least ten-fold in LD over HD granulocytes without sepsis-SIRS differences. Degranulation markers in blood were comparable in sepsis and SIRS. Higher expression of early developmental genes in sepsis than SIRS was more pronounced in LD and less in HD than total granulocytes. Only the cell membrane protein encoding genes CXCR2 and CEACAM4 were more highly expressed in SIRS than sepsis. By qRT-PCR, the azurophilic granule genes CD63 and PLAC8 showed higher sepsis than SIRS levels in LD granulocytes and PLAC8 also in total granulocytes where its discriminatory performance resembled C-reactive protein (CRP). Conclusions: Transcriptional programs of early terminal granulocytic differentiation distinguish sepsis from SIRS due to both higher counts of immature granulocytes and elevated expression of early developmental genes in sepsis. The sustained expression of PLAC8 in mature granulocytes likely accounts for its selection in the whole blood SeptiCyte™ LAB test. Total granulocyte PLAC8 rivals CRP as sepsis biomarker. However, infection-specific transcriptional pathways, that differentiate sepsis from sterile stress-induced granulocytosis more reliably than CRP, remain to be identified. [ABSTRACT FROM AUTHOR]

The document is an erratum for a paper titled "Restrictive versus standard IV fluid therapy in adult ICU patients with septic shock" published in Acta Anaesthesiologica Scandinavica. The correction addresses errors in estimates for days alive without life support, with the corrected posterior probability of benefits with restrictive IV fluid being 39%. The authors also updated Figures 10-12 to reflect the correct orientation of the horizontal axis. The correction does not impact the overall interpretations or conclusions of the study. [Extracted from the article]

The enzyme, insulin regulated aminopeptidase (IRAP), is expressed in multiple immune cells such as macrophages, dendritic cells and T cells, where it plays a role in regulating the innate and adaptive immune response. There is a genetic association between IRAP and survival outcomes in patients with septic shock where a variant of its gene was found to be associated with increased 28-day mortality. This study investigated the role for IRAP in a lipopolysaccharide (LPS)-induced inflammatory response which is thought to model facets of the systemic inflammation observed in the early stages of human gram-negative sepsis. The frequencies and activation of splenic immune cell populations were investigated in the IRAP knockout (KO) mice compared to the wildtype controls over a period of 4-, 24-, or 48-hours following LPS stimulation. Dendritic cells isolated from the spleen of female IRAP KO mice, displayed significant increases in the activation markers CD40, CD86 and MHCII at 24 hours after LPS induction. A modest heightened pro-inflammatory response to LPS was observed with increased expression of activation marker CD40 in M1 macrophages from male IRAP knockout mice. Observations in vitro in bone marrow-derived macrophages (BMDM) revealed a heightened pro-inflammatory response to LPS with significant increases in the expression of CD40 in IRAP deficient cells compared with BMDM from WT mice. The heightened LPS-induced response was associated with increased pro-inflammatory cytokine secretion in these BMDM cells. A genotype difference was also detected in the BMDM from female mice displaying suppression of the LPS-induced increases in the activation markers CD40, CD86, CD80 and MHCII in IRAP deficient cells. Thus, this study suggests that IRAP plays specific time- and sex-dependent roles in the LPS-induced inflammatory response in dendritic cells and macrophages. [ABSTRACT FROM AUTHOR]

Fluid management remains a critical challenge in the treatment of septic shock, with individualized approaches lacking. This study aims to develop a statistical model based on transcriptomics to identify subgroups of septic shock patients with varied responses to fluid strategy. The study encompasses 494 septic shock patients. A benefit score is derived from the transcriptome space, with higher values indicating greater benefits from restrictive fluid strategy. Adherence to the recommended strategy is associated with a hazard ratio of 0.82 (95% confidence interval: 0.64–0.92). When applied to the baseline hospital mortality rate of 16%, adherence to the recommended fluid strategy could potentially lower this rate to 13%. A proteomic signature comprising six proteins is developed to predict the benefit score, yielding an area under the curve of 0.802 (95% confidence interval: 0.752–0.846) in classifying patients who may benefit from a restrictive strategy. In this work, we develop a proteomic signature with potential utility in guiding fluid strategy for septic shock patients. Fluid management in septic shock lacks personalized approaches, which are critical for improving patient outcomes. Here, the authors show that a proteomic signature can help identify patients who may benefit from a restrictive fluid strategy, potentially reducing hospital mortality rates. [ABSTRACT FROM AUTHOR]

Introduction: Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients. Methods: Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA. Ethics and dissemination: The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025. Trial registration: Trial registration number:NCT05833607. https://clinicaltrials.gov/study/NCT05833607. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the protective effects of anisodamine (654-1/654-2) against acute kidney injury (AKI) in LPS-induced septic shock rats and explore its molecular mechanisms. Methods: 56 rats were randomly divided into 8 groups: control, LPS, LPS + 654-1, and LPS + 654-2 (1.25, 2.5 and 5 mg/kg). The model was evaluated by monitoring MAP, HR, and plasma LD levels. ELISA and biochemical assay kits were used to measure the levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-a) and kidney injury markers (BUN and CRE). Additionally, RNA-seq and bioinformatic analysis were performed to explore the mechanism of action of 654-1/654-2, and verification was conducted by western blotting and RT-PCR. Results: 654-1/654-2 significantly restored the levels of MAP, HR, and plasma LD in septic shock rats. Furthermore, 654-1/654-2 (5 mg/kg) effectively ameliorated LPS-induced kidney structural damage and exhibited a dose-dependent reduction in levels of inflammatory cytokines and kidney injury markers. In addition, RNA-seq, WB, and RT-PCR analyses revealed that 654-1/654-2 exerted its effects by inhibiting the expressions of the NF-κB and MAPK pathways and activating the Pi3K/Akt/Bcl-2 signaling pathway, thereby mitigating AKI. Discussion: This study suggested that 654-1/654-2 could alleviate AKI in septic shock rats by improving inflammation invasion and cell apoptosis. Notably, 654-1/654-2 collectively suppressed inflammation response through the p38/JNK/AP-1/NF-κB pathway. Additionally, 654-1 promotes survival signaling via the Pi3K/Akt/Bcl-2 pathway, whereas 654-2 reduces apoptosis through the P53/Bax pathway. These findings provided a theoretical basis for the clinical application of 654-1/654-2 in treating organ damage caused by septic shock. [ABSTRACT FROM AUTHOR]

Sepsis and septic shock remain global healthcare problems associated with high mortality rates despite best therapy efforts. Circulating biomarkers may identify those patients at risk for poor outcomes, however, current biomarkers, most prominently lactate, are non-specific and have an inconsistent impact on prognosis and/or disease management. Activation of the renin-angiotensin- system (RAS) is an early event in sepsis patients and elevated levels of circulating renin are more predictive of worse outcomes than lactate. The precursor protein Angiotensinogen is another key component of the circulating RAS; it is the only known substrate for renin and the ultimate source of the vasopressor Angiotensin II (Ang II). We postulate that lower Angiotensinogen concentrations may reflect a dysfunctional RAS characterized by high renin concentrations but attenuated Ang II generation, which is disproportionate to the high renin response and may compromise adequate support of blood pressure and tissue perfusion in septic patients. The current study compared the association between serum Angiotensinogen with mortality to that of lactate and renin in the VICTAS cohort of sepsis patients at baseline (day 0) by receiver operating characteristic (ROC) and Kaplan–Meier curve analyses. Serum concentration of Angiotensinogen was more strongly associated with 30-day mortality than either the serum concentrations of renin or lactate in sepsis patients. Moreover, the clinical assessment of Angiotensinogen may have distinct advantages over the typical measures of renin. The assessment of intact Angiotensinogen may potentially facilitate more precise therapeutic approaches (including exogenous angiotensin II) to restore a dysfunctional RAS and improve patient outcomes. Additional prospective validation studies are clearly required for this biomarker in the future. [ABSTRACT FROM AUTHOR]

Background: Voriconazole (VRZ) is involved in a variety of drug‒drug interactions (DDIs), but few studies have reported adverse events (AEs) associated with the DDIs of VRZ. The primary goal of this study was to analyse the potential risk factors for AEs caused by DDIs between VRZ and other drugs via the OpenVigil FDA platform and to provide a reference for preventing VRZ DDIs and monitoring clinically related adverse drug events. Methods: A retrospective pharmacovigilance study was conducted to investigate the AEs related to DDIs between VRZ and four categories of drugs: proton pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressants, and other antibacterial drugs. AE information for the target drugs from the first quarter of 2004 to the third quarter of 2022 was downloaded from the OpenVigil FDA data platform. Four frequency statistical models—the reporting ratio method, Ω shrinkage measure model, combination risk ratio model, and the chi-square statistics model—were used to analyse the AEs related to DDIs and evaluate the correlation and influence of sex and age between the drug(s) and the target AEs detected. Results: A total of 38 drugs were included, with 262 AEs detected by at least one of the four models and 48 AEs detected by all four models. Some 77 detected AEs were significantly positively correlated with DDIs and were related to higher reporting rates of AEs than when used alone. Graft-versus-host disease was the AE that had the strongest correlation with the drug interaction between VRZ and immunosuppressants (tacrolimus, mycophenolate mofetil, cyclophosphamide, and cyclosporine), and multiple organ dysfunction syndrome was correlated with VRZ in combination with other antibacterial drugs (linezolid, meropenem, cefepime, and vancomycin). Significant sex and age differences in the target AEs were detected for five and nine target drugs, respectively. For VRZ in combination with linezolid, aggravated conditions and respiratory failure should be given more attention in male patients, and mycophenolate mofetil and respiratory failure in female patients. When conditions are aggravated, febrile neutropenia and septic shock should be of particular concern in patients over 18 years of age who use VRZ in combination with ceftazidime, ciprofloxacin, or cytarabine. In patients aged under 18, septic shock should be considered when VRZ is used in combination with meropenem and dexamethasone. Conclusion: AEs related to DDIs should receive more attention when VRZ is used in combination with PPIs (renal impairment), NSAIDs (constipation and renal failure), immunosuppressants (graft versus host disease, septic shock) and other antibacterial drugs (multiple organ dysfunction syndrome, febrile neutropenia, and respiratory failure). Considering the influence of sex and age differences in VRZ DDIs, these factors need to be considered when assessing the risk of AEs in patients receiving VRZ and other drugs. [ABSTRACT FROM AUTHOR]

Chlamydia psittaci pneumonia (CPP) exhibits similar characteristics as of COVID-19 with respect to clustering outbreaks and onset symptoms. This study is aimed at exploring the different clinical manifestations of both pneumonias to establish a simple nomogram to distinguish them. This multicenter, retrospective, case–control study compared two independent cohorts of patients with CPP or COVID-19. The risk factors of CPP were analyzed using multivariate logistic regression, which was used to establish the nomogram. Both patients with CPP and COVID-19 exhibited similar clinical symptoms. As compared to patients with COVID-19, a higher proportion of patients with CPP had nervous system symptoms. Patients with CPP had higher inflammatory indicators, creatine kinase, and lower lymphocyte and albumin. They also had lower proportions of ground-glass opacity and bilateral lung involvement than COVID-19 patients. Furthermore, patients with CPP had higher 30 day mortality as well as higher rates of severe pneumonia, septic shock, and ICU admission. Multivariate logistic regression showed that nervous system symptoms, lymphocytes, creatine kinase, bilateral lung lesions, and ground-glass opacity were risk factors for CPP. Incorporating these five factors, the nomogram achieved good concordance index of 0.989 in differentiating CPP from COVID-19, and had well-fitted calibration curves. Despite similar clinical characteristics, nervous system symptoms, lymphocyte, creatine kinase, lesions in bilateral lungs, and ground-glass opacity may help in differentiating the pneumonias. These were combined into a clinically useful nomogram for rapid and early identification of CPP to avoid misdiagnosis and help in the decision-making process. [ABSTRACT FROM AUTHOR]

Over the past 15 years, there has been a noticeable uptick in incidents involving children ingesting multiple magnetic foreign bodies which can cause injuries and gastrointestinal complications including death. The current study aimed to identify the prevalence, clinical presentation, and management of single or multiple magnet ingestions. A retrospective multi-central cross-sectional study was conducted to include all pediatric patients < 18 years presented to the emergency department with ingestion of single or multiple magnets and admitted across hospitals in Qatar, UAE, KSA, Tunisia, and Turkey between January 2011 and December 2021. Demographics, symptoms, management, and outcomes were analyzed. There were 189 magnet ingestions, of which 88 (46.6%) were multiple magnet ingestions. Most patients (55.6%) were male, and the median age was 3.9 (IQR 2–7) years. An abdominal X-ray was obtained in all cases. 119 (62%) patients were conservatively treated, 53 (28%) required surgical intervention and 17 (8.9%) underwent gastroscopy. None of the patients with single magnet ingestions experienced morbidity or severe outcomes. Multiple magnet ingestions led to significant morbidity including hospitalizations, perforations (44.3%), severe intestinal necrosis (19.3%), peritonitis (13.6%), severe abdominal infection (10.2%), and septic shock (4.5%). The rate of surgical intervention (59.1% vs. 1.0%) and gastroscopy (15.9% vs. 3.0%) was significantly higher in the multiple ingestion group compared to the single magnet ingestion group. No deaths were identified. A high risk of serious complications, including the need for surgery to remove the magnets and substantial morbidity may result from swallowing more than one magnet. Magnet safety requirements, public education, and improved legislation are urgently required. [ABSTRACT FROM AUTHOR]

This study assessed the impact of urinary tract anomalies or a history of upper urinary tract surgery (UTAS) on the minimally invasive endoscopic combined intrarenal surgery (mini-ECIRS) outcomes. Data from 1432 patients undergoing ECIRS for urolithiasis at three Japanese tertiary institutions between 2015 and 2021 were analyzed, with patients categorized into those with normal urinary tracts (non-UTAS) and those with UTAS (UTAS). We retrospectively examined the association between the UTAS and perioperative outcomes in mini-ECIRS. Of the 1096 cases in the final analysis, 1035 and 61 were identified as non-UTAS and UTAS, respectively. Stone-free rate (residual fragments > 2 mm, 62.8% vs. 62.7%), operation time (110.5 vs. 115.0 min), and hospital stay duration (5.6 vs. 5.7 days) showed no significant differences between non-UTAS and UTAS. The UTAS group demonstrated significantly higher rates of preoperative pyuria (86.2% vs. 71.1%), preoperative urinary tract infection (32.8% vs. 15.5%), preoperative stenting (52.5% vs. 31.0%), and preoperative nephrostomy (24.6% vs. 9.2%). However, the postoperative fever (26.3% vs. 25.0%) or septic shock (1.9% vs. 0%) were comparable between non-UTAS and UTAS. Stone burden and the number of calyces involved were significantly associated with a low stone-free rate (P < 0.001). Younger age, female sex, solitary stones, number of calyces involved, preoperative urinary tract infection, and absence of preoperative nephrostomy were identified as risk factors for perioperative complications. The UTAS was not associated with stone-free outcomes or perioperative complications. Mini-ECIRS demonstrated comparable stone-free outcomes and safety in patients with UTAS and those with normal urinary tracts. [ABSTRACT FROM AUTHOR]

Background & objective: The Infectious Disease Society of America guidelines recommend vancomycin trough levels of 15–20 mg/L for severe methicillin-resistant Staphylococcus aureus. However, recent consensus guidelines of four infectious disease organizations no longer recommend vancomycin dosing using minimum serum trough concentrations. Therefore, this study aimed to evaluate the impact of low (< 15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough levels on clinical outcomes in adult patients with sepsis or gram-positive bacterial infections. Method: A systematic literature review from inception to December 2022 was conducted using four online databases, followed by a meta-analysis. The outcomes of interest included clinical response/efficacy, microbial clearance, length of ICU stay, treatment failure, nephrotoxicity, and mortality. Results: Fourteen cohort studies met the inclusion criteria from which vancomycin trough concentration data were available for 5,228 participants. Our analysis found no association between vancomycin trough levels and clinical response [OR = 1.06 (95%CI 0.41–2.72], p = 0.91], microbial clearance [OR = 0.47 (95% CI 0.23–0.96), p = 0.04], ICU length of stay [MD=-1.01 (95%CI -5.73–3.71), p = 0.68], or nephrotoxicity [OR = 0.57 (95% CI 0.31–1.06), p = 0.07]. However, low trough levels were associated with a non-significant trend towards a lower risk of treatment failure [OR = 0.89 (95% CI 0.73–1.10), p = 0.28] and were significantly associated with reduced risk of all-cause mortality [OR = 0.74 (95% CI 0.62–0.90), p = 0.002]. Conclusion: Except for a lower risk of treatment failure and all-cause mortality at low vancomycin trough levels, this meta-analysis found no significant association between vancomycin trough levels and clinical outcomes in adult patients with sepsis or gram-positive bacterial infections. [ABSTRACT FROM AUTHOR]

Exploration of the incidence and outcomes of Acute Kidney Injury (AKI) broadly, and sepsis associated AKI specifically, in Aboriginal and Torres Strait Islander (First Nations) people has been limited. We compared a nested cohort of First Nations people drawn from a multinational randomised controlled trial of hydrocortisone in septic shock, to a cohort matched for age, sex and severity of illness. Acute Kidney Injury was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, as well as incident use of kidney replacement therapy (KRT). Major Adverse Kidney Events (MAKE) were described as the composite of death, new dialysis requirement or persisting kidney dysfunction at hospital discharge. A cohort of 57 Aboriginal and/or Torres Strait Islander patients with septic shock was identified. 91.2% (52) of the First Nations cohort met KDIGO criteria for Stage 1 AKI or greater and 63% (36) met Stage 3 criteria. 59.6% (34) of the First Nations required dialysis as compared to 45.6% (26) in the matched cohort. 60.7% (34) of First Nations participants met criteria for MAKE at hospital discharge. The proportions requiring dialysis at 6, 12 and 24 months were 8.3%, 9.1% and 6.9% respectively. The incidences of AKI and MAKE reported in this First Nations cohort are substantially higher than in previously published cohorts of patients with sepsis, even those that use sensitive definitions of AKI. Measures to promote better management of infectious diseases in First Nations communities are required. [ABSTRACT FROM AUTHOR]

Background: Peripheral veno-arterial extracorporeal membrane oxygenation (pECMO) has become the first-line device in refractory cardiogenic shock (rCS). Some pECMO complications can preclude any bridging strategies and a peripheral-to-central ECMO (cECMO) switch can be considered as a bridge-to-decision. We conducted this study to appraise the in-hospital survival and the bridging strategies in patients undergoing peripheral-to-central ECMO switch. Methods: This retrospective monocenter study included patients admitted to a ECMO-dedicated intensive care unit from February 2006 to January 2023. Patients with rCS requiring pECMO switched to cECMO were included. Patients were not included when the cECMO was the first mechanical circulatory support. Results: Eighty patients, with a median [IQR25-75] age of 44 [29–53] years at admission and a female-to-male sex ratio of 0.6 were included in the study. Refractory pulmonary edema was the main switching reason. Thirty patients (38%) were successfully bridged to: heart transplantation (n = 16/80, 20%), recovery (n = 10/80, 12%) and ventricle assist device (VAD, n = 4/30, 5%) while the others died on cECMO (n = 50/80, 62%). The most frequent complications were the need for renal replacement therapy (76%), hemothorax or tamponade (48%), need for surgical revision (34%), mediastinitis (28%), and stroke (28%). The in-hospital and one-year survival rates were 31% and 27% respectively. Myocardial infarction as the cause of the rCS was the only variable independently associated with in-hospital mortality (HR 2.5 [1.3–4.9], p = 0.009). Conclusions: The switch from a failing pECMO support to a cECMO as a bridge-to-decision is a possible strategy for a very selected population of young patients with a realistic chance of heart function recovery or heart transplantation. In this setting, cECMO allows patients triage preventing from wasting expensive and limited resources. [ABSTRACT FROM AUTHOR]

Lactate significantly impacts immune cell function in sepsis and septic shock, transcending its traditional view as just a metabolic byproduct. This review summarizes the role of lactate as a biomarker and its influence on immune cell dynamics, emphasizing its critical role in modulating immune responses during sepsis. Mechanistically, key lactate transporters like MCT1, MCT4, and the receptor GPR81 are crucial in mediating these effects. HIF-1a also plays a significant role in lactate-driven immune modulation. Additionally, lactate affects immune cell function through post-translational modifications such as lactylation, acetylation, and phosphorylation, which alter enzyme activities and protein functions. These interactions between lactate and immune cells are central to understanding sepsis-associated immune dysregulation, offering insights that can guide future research and improve therapeutic strategies to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Critical illness causes disturbances in lipid metabolism. Here, we investigated the levels of apolipoprotein A-IV (apoA-IV), a regulator of triglyceride and cholesterol metabolism, in human sepsis. ApoA-IV (analyzed in 156 patients with systemic inflammatory response syndrome (SIRS)/sepsis) and cholesteryl ester (CE) (analyzed in 121 of these patients) were lower in patients compared to 43 healthy controls. In contrast, triglyceride (TG) levels were elevated in patients. ApoA-IV levels in plasma of the patients did not correlate with these lipids. Patients with SIRS, sepsis or septic shock had comparable apoA-IV, TG, CE and free cholesterol (FC) levels. Patients on dialysis had significantly lower CE levels, whereas apoA-IV levels did not change much. CE levels were elevated in patients with viral sepsis due to SARS-CoV-2 infection in comparison to SIRS/sepsis patients not infected by this virus. CE levels correlated negatively with procalcitonin, interleukin-6 and bilirubin, while TGs were positively associated with bilirubin and C-reactive protein. ApoA-IV, TG, CE and FC levels were not associated with bacterial infection or survival. In conclusion, this analysis suggests that CE levels decline in sepsis-related renal failure and also shows that plasma apoA-IV and CE levels are early biomarkers of sepsis. [ABSTRACT FROM AUTHOR]

BACKGROUND: A multitude of required and non-necessary changes are linked to infections, and in extreme situations, these changes necessitate prompt attention as infections can be life-threatening and cause serious organ malfunction, which can lead to organ failure and death. Sepsis is a very common and complicated condition and is faced by both the developing and developed world. The global epidemiological burden of sepsis is difficult to ascertain. It is estimated to affect more than 30 million people worldwide every year, potentially leading to 6 million deaths. MATERIALS AND METHODS: A hospital based prospective study was conducted patients admitting in MICU and RICU at Basaveshwara Medical College Hospital, Chitradurga during the study period of 18 months from August 2022 to February 2024. Clearance from institution ethics committee was taken before the study was started. An informed consent was taken before including the study subjects in to the study. RESULTS: There was no statistically significant difference in cases with neutrophil lymphocyte ratio of less and more than 3. There was a statistically significant difference in the neutrophil count in cases with neutrophil lymphocyte ratio of less than 3 and more than 3. There was no statistically significant difference between the cases with neutrophil lymphocyte ratio of less and more than 3 with respect to lymphocyte counts at admission. CONCLUSION: This study was undertaken in order to study neutrophil lymphocyte ratio as a prognostic marker in cases of severe sepsis. This study had shown that, NLR was shown to be an important and readily available marker prognosis of sepsis. But this study is not without limitations. This used a convenience sample method where study results cannot be generalized. [ABSTRACT FROM AUTHOR]

Background: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Magnesium reportedly has immunomodulatory effects and is associated with dysregulated host response to infection and the pathophysiology of sepsis. Previous studies reported that hypomagnesemia was associated with lactic acidosis in sepsis, increased incidence of sepsis or septic shock in critically ill patients, and increased mortality in sepsis. Thus, this study is being conducted to explore the association between serum magnesium levels and coagulopathy in sepsis, outcomes. Materials: This cross-sectional study was performed on 40 Sepsis Cases Admitted in Intensive care Unit, Kempegowda institute of medical sciences during a 12-month period. SOFA score was calculated. Serum magnesium levels were estimated. Sepsis cases were categorized based on serum magnesium levels as low, normal, high on the day of diagnosis of sepsis. ISTH criteria will be used for diagnosis of overt DIC/coagulopathy in sepsis cases during the course in the hospital. Serum magnesium levels was independently associated with both coagulopathy/DIC and clinical outcome of sepsis cases. The data was collected and compiled in MS Excel. Descriptive statistics has been used to present the data. To analyse the data SPSS (Version 26.0) was used. Significance level was fixed as 5% (a = 0.05. Qualitative variables are expressed as frequency and percentages and Quantitative variables are expressed as Mean and Standard Deviation. To compare the association between numerical and categorical variables, student t test was used. Observation: The mean age of the study participants was found to be 58.75+17.299. 75% of the study participants were males. The mean serum magnesium levels were found to be 1.8798+0.56902. 67.5% of the study participants had low grade DIC and 32.5% of the study participants had overt DIC. The mortality rate in the present study was found to be 35%. The mean Serum magnesium of the study participants with Overt DIC were found to be lower than low grade DIC study participants (1.37+0.47vs2.12+0.44; P value=0.000). The mean Serum magnesium of the study participants who died were found to be lower than that of study participants who were discharged (1.59+0.60vs2.03+0.49; P value=0.019). Conclusion: Serum magnesium was found to be inversely related to DIC in sepsis patients and hypomagnesemia is associated with poor clinical outcome in sepsis patients. Consequently, treatment of hypomagnesemia may be a viable therapeutic approach for the prevention and management of coagulopathy in sepsis. [ABSTRACT FROM AUTHOR]

Objective: To assess the predictive abilities of Doppler‐based resistive index and plasma biomarkers of endothelial cell activation in identifying persistent acute kidney injury (pAKI) among patients with septic shock. Method: Patients diagnosed with septic shock were categorized into none AKI (n = 25), transient AKI (tAKI, n = 47), and pAKI (n = 48) groups. Kidney function parameters (urine output, serum creatinine, and serum urea) were measured within the initial 24 h upon intensive care unit (ICU) admission. The Doppler‐based resistive index, and the plasma biomarkers [fractalkine, soluble E‐Selectin (sE‐Selectin), and soluble intercellular adhesion molecule‐1 (sICAM‐1)] were evaluated upon admission to the ICU. Results: The predictive capacity of Doppler‐based resistive index for distinguishing pAKI at day 3 from none AKI/tAKI in septic shock patients was moderate, with sensitivity of 47.92% and specificity of 76.39%. Fractalkine levels displayed significant differences across groups and exhibited a favorable predictive ability for pAKI at day 3 (AUC = 0.800), while sE‐Selectin and sICAM‐1 showed moderate predictive abilities (AUC = 0.636 and 0.634, respectively). Comparative analysis of predictive models demonstrated that incorporating kidney function parameters, Doppler‐based resistive index, and plasma biomarkers yielded the highest AUC of 0.903, followed closely by the model utilizing serum creatinine, urine output, and plasma fractalkine, with an AUC of 0.896. Conclusion: Integrating kidney function parameters, along with Doppler‐based resistive index and plasma biomarkers of endothelial cell activation, yielded the strongest predictive model for pAKI. Additionally, the combination of serum creatinine, urine output, and plasma fractalkine shows promise in risk assessment and management strategies for pAKI. [ABSTRACT FROM AUTHOR]

Background • Septic shock poses a significant threat to life safety, with continuous blood purification as a primary treatment modality. Enhancing the therapeutic efficacy of continuous blood purification holds crucial implications for septic shock management. Objective • This study aims to observe the therapeutic efficacy of glucocorticoid-assisted continuous blood purification (CBP) in septic shock patients, providing valuable insights for future clinical treatments. Methods • A total of 200 septic shock patients admitted between October 2020 and January 2023 were selected and categorized into an observation group and a control group. The observation group (n=118) received glucocorticoid- assisted CBP, while the control group (n=82) received standard CBP. Changes in various parameters, including pH, blood urea nitrogen, serum creatinine, bicarbonate, inflammatory cytokines, T lymphocyte subsets, mean arterial pressure, pulmonary vascular permeability index, intrathoracic blood volume index, and cardiac index, were recorded before and after treatment. Complications during treatment were also documented. Results • Post-treatment bicarbonate and cardiac index showed no significant difference between the two groups (P > .05). However, the observation group exhibited higher pH, mean arterial pressure, CD3+, CD4+, and CD8+ levels than the control group, as well as lower blood urea nitrogen, serum creatinine, inflammatory cytokines, and CD4+/CD8+ ratio (P < .05). Moreover, no notable difference in complication rates was identified between the groups (P > .05). Conclusions • Glucocorticoids-assisted continuous blood purification therapy effectively improves vital signs and immune function in septic shock patients, offering a more reliable guarantee for patient life safety. [ABSTRACT FROM AUTHOR]

Background: Surgery often leads to bleeding associated with hypofibrinogenemia. Supplementation with fibrinogen concentrate appears to be effective and safe, although findings from studies are inconsistent. The primary aim of this study was to assess the safety of fibrinogen concentrate during the perioperative period. Methods: This single-centre, prospective, observational study included adult patients undergoing scheduled or emergency surgery related to bleeding coagulopathy and the administration of fibrinogen concentrate. Patients were followed until their discharge from the institution. Comprehensive data were collected, including age, sex, type of surgery, associated comorbidities, anticoagulant and/or anti-aggregating therapy, and the number of blood transfusions. Laboratory data on plasma fibrinogen concentration, haemoglobin, and platelet count before and after surgery were also collected. The primary outcomes were the mortality rate at discharge and any reported thrombotic or thromboembolic events, including deep vein thrombosis, pulmonary embolism, and myocardial infarction. Results: The study included 91 adult patients who had undergone surgery, with 29 surgeries (32%) conducted in an emergency setting. The mean age was 59.2 years, and 53.8% were male. Major bleeding occurred in 29 cases, mainly in older males and those on anticoagulant therapy. The pre-operative fibrinogen level averaged 161 mg/dL, and the average dosage of fibrinogen concentrate administered was 2.7 g. Eight patients died (8.8%), mostly due to septic or cardiogenic shock, with deaths being more frequent in emergency settings. Thromboembolic events occurred in eight patients, none of whom died. No additional adverse events directly related to the administration of fibrinogen concentrate were reported. Conclusions: Our findings suggest a favourable safety profile for fibrinogen concentrate in surgical patients, as evidenced by a low incidence of deaths and thromboembolic events, which were primarily attributed to other factors. Future research should strive to increase statistical robustness to further illuminate clinically significant patient safety measures. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) are reported to have an increased risk of developing severe infections, leading to hospitalizations with sepsis. However, data regarding the impact of comorbid NAFLD on in-hospital outcomes of patients with sepsis is scarce. Methods: This nationwide retrospective observational study using discharge data from the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), and Agency for Healthcare Research and Quality included 21,057,911 adult patients who were admitted to hospitals in the United States between 2000 and 2019 with a primary discharge diagnosis of sepsis. These patients were categorized according to the presence or absence of comorbid NAFLD. The twenty-year trend of nationwide NAFLD prevalence among sepsis inpatients was elucidated. Multivariable logistic regression analysis was used to analyze NAFLD's impact on sepsis outcomes. Results: In the twenty-year study period, the prevalence of NALFD among sepsis inpatients trended up from 1.2% in 2000 to 4.2% in 2019. Similar trends were observed in regional analysis. While overall sepsis mortality decreased, comorbid NAFLD in sepsis patients was consistently associated with a higher adjusted in-hospital all-cause mortality rate (adjusted odds ratio (OR), 1.19; 95% confidence interval (CI), 1.07–1.32), higher odds of developing septic shock, and higher likelihood of development of multi–organ dysfunction. Conclusions: Comorbid NAFLD in the stage of NASH or cirrhosis is associated with higher in-hospital all-cause mortality and worse clinical outcomes in sepsis inpatients. Addressing this rising epidemic will be of paramount importance to improve sepsis in-hospital outcomes. [ABSTRACT FROM AUTHOR]

Background/Objectives: Sepsis and septic shock remain significant contributors to high early mortality rates among patients admitted to the emergency department (ED). The objective of this study was to identify among newer biomarkers those with the highest sensitivity in early mortality prediction. Methods: This prospective, unicentric, observational study enrolled 47 adult patients admitted to the ED between November 2020 and December 2022. This study monitored the kinetics of the older and newer biomarkers, including azurocidin (AZU1), soluble triggering receptor expressed on myeloid cells (sTREM), soluble urokinase-type plasminogen activator receptor (suPAR), high-sensitivity C-reactive protein (hsCRP), procalcitonin (PCT), and interleukin-6 (IL-6), and their capacity in predicting mortality. Results: SuPAR showed the most significant predictive utility for early prognosis of mortality in the ED, with an area under the curve (AUC) of 0.813 (95% CI: 0.672 to 0.912), a cutoff value > 8168 ng/mL, sensitivity of 75%, and specificity of 81.48% (p < 0.001). IL-6 and PCT showed comparable prognostic accuracy, whereas hsCRP and AZU1 demonstrated lower predictive performance. Conclusions: In our study, suPAR, IL-6, and PCT showed good predictive value for short-term mortality in sepsis and septic shock patients. [ABSTRACT FROM AUTHOR]

Sepsis poses a significant challenge due its lethality, involving multiple organ dysfunction and impaired immune responses. Among several factors affecting sepsis, monocytes play a crucial role; however, their phenotype, proteomic profile, and function in septic shock remain unclear. Our aim was to fully characterize the subpopulations and proteomic profiles of monocytes seen in septic shock cases and discuss their possible impact on the disease. Peripheral blood monocyte subpopulations were phenotype based on CD14/CD16 expression by flow cytometry, and proteins were extracted from the monocytes of individuals with septic shock and healthy controls to identify changes in the global protein expression in these cells. Analysis using 2D-nanoUPLC-UDMSE identified 67 differentially expressed proteins in shock patients compared to controls, in which 44 were upregulated and 23 downregulated. These proteins are involved in monocyte reprogramming, immune dysfunction, severe hypotension, hypo-responsiveness to vasoconstrictors, vasodilation, endothelial dysfunction, vascular injury, and blood clotting, elucidating the disease severity and therapeutic challenges of septic shock. This study identified critical biological targets in monocytes that could serve as potential biomarkers for the diagnosis, prognosis, and treatment of septic shock, providing new insights into the pathophysiology of the disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the utility of Pulse index Contour Continuous Cardiac Output (PiCCO) monitoring in critically ill patients. Study Design: Cross-sectional study. Setting: Intensive Care Unti of Sindh Institute of Urology and Transplant, Karachi, Pakistan. Period: October 2022 to March 2023. Methods: Patients presenting with various types of shock, requiring high-dose vasopressors or inotropes, and not responding to initial fluid therapy were analyzed. Demographic details, SOFA score, APACHE score, and invasive hemodynamic parameters using the PiCCO system were documented. Results: Out of 142 ICU admissions, 38 patients were included in the study. Most patients were males (73%) with a median age of 39 years. Significant changes were observed in the cardiac index, cardiac performance index, global ejection fraction, and systemic vascular resistance index (SVRI), all with p-values less than 0.05. The interventions included the initiation of inotropes in 22 patients (57.8%), diuretics in 4 patients (10.5%), and intravenous fluids in 19 patients (50%). Additionally, vasopressor doses were adjusted in 18 patients (47.3%). Initially, patients were presumed to have pure septic shock based on CO2 gap, mixed venous saturation, and echocardiographic assessment. However, after applying PiCCO monitoring, the diagnosis was revised to mixed shock in 21 patients (55.2%). Conclusion: PiCCO monitoring appears to be a valuable tool in the ICU for managing patients with complex hemodynamic profiles, facilitating targeted interventions that lead to significant improvements in hemodynamic stability. [ABSTRACT FROM AUTHOR]

Purpose: Specialized pressure transducers for arterial pulse waveform analysis (S-APWA) devices are dedicated kits connected to an arterial pressure catheter that monitors hemodynamic parameters, such as cardiac output, pulse pressure variation, and stroke volume variation, less invasively. While the association between the use of S-APWA devices and clinical outcomes in perioperative patients has been previously evaluated, its assessment in patients with septic shock remains inadequate. Materials and Methods: This retrospective cohort study utilized a nationwide Diagnosis Procedure Combination database in Japan. Adult patients with septic shock admitted to the intensive care unit (ICU) with arterial pressure catheter placement on the admission day from August 2012 to February 2021 were included. Hospitalizations meeting the eligibility criteria were categorized into groups based on S-APWA device usage. The primary outcome, evaluated using Cox regression analysis, was 30-day all-cause mortality in the propensity score overlap-weighted population. Secondary outcomes included in-hospital mortality, ICU duration, and overall hospital stay. Results: Among 5130 eligible hospitalizations, 643 were in the S-APWA group and 4487 were in the conventional pressure transducer group. Cox regression analysis within the propensity score overlap-weighted population showed no significant difference in 30-day mortality (adjusted hazard ratio: 0.94; 95% confidence interval: 0.9-1.38; P =.58). Logistic regression analysis indicated no significant differences in the in-hospital mortality. While the S-APWA group had prolonged ICU stays, no significant difference in the overall hospital stay was observed according to linear regression analyses. Conclusions: Our study found no significant association between S-APWA use and 30-day mortality in patients with septic shock. These findings offer insights into optimizing monitoring systems in ICUs. [ABSTRACT FROM AUTHOR]

Objectives: To investigate characteristics and outcomes of critically ill cancer patients with marked hyperferritinemia. Methods: A single‐center retrospective analysis comprising cancer patients with a ferritin level >10.000 μg/L treated in the intensive care unit (ICU) between 2012 and 2022 was conducted. Results: A total of 117 patients were included in the analysis. The median age was 59 years (range: 15–86 years). Females accounted for 48% of cases. 90% of patients had a hematologic malignancy. The median maximum ferritin level was 27.349 μg/L (range: 10.300–426.073 μg/L). The diagnostic criteria of septic shock were fulfilled in 51% of cases; 31% of patients had hemophagocytic lymphohistiocytosis (HLH) according to the HLH‐2004 criteria. Mechanical ventilation, renal replacement therapy and the use of vasopressors were necessary in 59%, 35% and 70% of cases, respectively. The ICU, hospital, 90‐day and 1‐year survival rates were 33.3%, 23.1%, 23.7% and 11.7%. Patients with septic shock had a worse survival than those without septic shock (p =.001); the survival of patients who fulfilled the HLH‐2004 criteria did not differ from those who did not (p =.88). Conclusion: Critically ill cancer patients with marked hyperferritinemia have poor outcomes. The present data may help to make informed decisions for this patient group. [ABSTRACT FROM AUTHOR]

Introduction: This systematic review aimed to assess the efficacy and safety of hydrocortisone, ascorbic acid, and thiamine (HAT) combination therapy in patients with sepsis and septic shock. Methods: We conducted a database search in MEDLINE, Embase, CENTRAL, Web of Science, and CNKI for randomised controlled trials (RCTs) comparing HAT against placebo/standard of care or against hydrocortisone in sepsis/septic shock patients. Outcomes included mortality, ICU/hospital length of stay (LOS), vasopressor durations, mechanical ventilation durations, change in SOFA at 72 h, and adverse events. RCT results were pooled in random-effects meta-analyses. Quality of evidence was assessed using GRADE. Results: Fifteen RCTs (N = 2,594) were included. At 72 h, HAT reduced SOFA scores from baseline (mean difference [MD] −1.16, 95% confidence interval [CI]: −1.58 to −0.74, I2 = 0%) compared to placebo/SoC, based on moderate quality of evidence. HAT also reduced the duration of vasopressor use (MD −18.80 h, 95% CI: −23.67 to −13.93, I2 = 64%) compared to placebo/SoC, based on moderate quality of evidence. HAT increased hospital LOS (MD 2.05 days, 95% CI: 0.15–3.95, I2 = 57%) compared to placebo/SoC, based on very low quality of evidence. HAT did not increase incidence of adverse events compared to placebo/SoC. Conclusions: HAT appears beneficial in reducing vasopressor use and improving organ function in sepsis/septic shock patients. However, its advantages over hydrocortisone alone remain unclear. Future research should use hydrocortisone comparators and distinguish between sepsis-specific and comorbidity- or care-withdrawal-related mortality. [ABSTRACT FROM AUTHOR]

Introduction Appendicitis in patients with hematologicalmalignancies presents with vague symptoms, thus requiring a high degree of suspicion for early diagnosis and treatment to prevent complications. Objectives The aim of this article was to describe the demographic, clinicoradiological, operative findings, and outcomes in patients with acute appendicitis with underlying hematological malignancies. Materials and Methods A retrospective review of pediatric patients with hematological malignancy who developed acute appendicitis was conducted. Medical records of patients were reviewed for patient demographics, disease status, signs, and symptoms at the time of diagnosis of acute appendicitis, and outcome. The laboratory, radiological, and histological findings were retrieved from the hospital records. Results Six (2.4%) patients developed acute appendicitis over the past 8 years among a total of 254 patients treated for hematological malignancies in the unit. Five patients had underlying acute lymphoblastic leukemia (ALL) and one had acutemyeloid leukemia (AML). Of the five patients, three were in postremission consolidation, one each in the delayed intensification and maintenance phase of chemotherapy. The child with AML was on induction chemotherapy for the first relapse at the time of diagnosis. Fever and abdominal pain were the common presenting symptoms. Diagnosis was made on ultrasound abdomen in five patients, and one patient was diagnosed on computed tomography. All patients underwent open appendectomy. Two patients had evidence of appendiceal perforation. Three patients had neutropenia at the time of developing appendicitis and underwent appendectomy regardless of the absolute neutrophil count (ANC). Five patients recovered well, and chemotherapy was restarted within 2 weeks of appendectomy. One patient developed a superficial surgical site infection. and one patient with relapsed AML expired due to refractory septic shock. Conclusion Acute appendicitis in patients with hematological malignancies can present with subtle signs and symptoms. Appendectomy can be safely performed irrespective of the ANC. [ABSTRACT FROM AUTHOR]

Background: Precise estimates of risk-adjusted increases in postoperative length of stay (LOS) associated with postoperative complications across a range of complications and operations are not available in the existing literature. Methods: Associations between preoperative characteristics, postoperative complications and postoperative LOS were tested using medians, interquartile ranges, and nonparametric rank sum tests in a retrospective cohort study using the 2005–2018 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) dataset. A negative binomial model was used with postoperative LOS as the dependent variable and preoperative characteristics and postoperative complications as independent variables. The model was applied to estimate each patient's postoperative LOS with and without each postoperative complication to measure the association between each complication and risk-adjusted change in postoperative LOS. Results: A total of 4,495,582 patients were included. After risk-adjustment, occurrence of each postoperative complication was associated with significantly increased postoperative LOS (between + 3.9 and + 20.1 days, p < 0.0001). The longest risk-adjusted postoperative LOS increases were associated with prolonged ventilator use (+ 20.1 days), wound disruption (+ 19.4 days), and acute renal failure (+ 17.1 days). Conclusion: Occurrence of any postoperative complication was associated with increased risk-adjusted postoperative LOS. Degree of increase varied by complication. These data could be useful for patient counseling, allocation of resources, discharge planning, and quality improvement efforts. [ABSTRACT FROM AUTHOR]

Purpose: Excessive tachycardia in resuscitated septic shock patients can impair hemodynamics and worsen patient outcome. We investigated whether heart rate (HR) control can be achieved without increased vasopressor requirements using the titratable highly selective, ultra-short-acting β1-blocker landiolol. Methods: This randomized, open-label, controlled trial was conducted at 20 sites in 7 European countries from 2018 to 2022 and investigated the efficacy and safety of landiolol in adult patients with septic shock and persistent tachycardia. Patients were randomly assigned to receive either landiolol along with standard treatment (n = 99) or standard treatment alone (n = 101). The combined primary endpoint was HR response (i.e., HR within the range of 80−94 beats per minute) and its maintenance without increasing vasopressor requirements during the first 24 h after treatment start. Key secondary endpoints were 28-day mortality and adverse events. Results: Out of 196 included septic shock patients, 98 received standard treatment combined with landiolol and 98 standard treatment alone. A significantly larger proportion of patients met the combined primary endpoint in the landiolol group than in the control group (39.8% [39/98] vs. 23.5% [23/98]), with a between-group difference of 16.5% (95% confidence interval [CI]: 3.4–28.8%; p = 0.013). There were no statistically significant differences between study groups in tested secondary outcomes and adverse events. Conclusion: The ultra-short-acting beta-blocker landiolol was effective in reducing and maintaining HR without increasing vasopressor requirements after 24 h in patients with septic shock and persistent tachycardia. There were no differences in adverse events and clinical outcomes such as 28-day mortality vs. standard of care. The results of this study, in the context of previous trials, do not support a treatment strategy of stringent HR reduction (< 95 bpm) in an unselected septic shock population with persistent tachycardia. Further investigations are needed to identify septic shock patient phenotypes that benefit clinically from HR control. [ABSTRACT FROM AUTHOR]

Background: Heart rate is crucial for patients with septic shock, but there are few studies on the scope of heart rate. Therefore, we studied the relationship between different heart rates and mortality of critically ill patients with septic shock, and explored the optimal heart rate range, in order to provide new insights for clinical treatment of septic shock. Methods: This retrospective study utilized time-series heart rate data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients with septic shock were identified as the Sepsis 3.0 criteria and received vasopressor therapy in the first 24 h since ICU admission. We calculated the time-weighted average heart rate (TWA-HR) based on the time-series data. The restricted cubic spline (RCS) analysis was employed to investigate the nonlinear relationship between heart rate and 28-day mortality, aiming to explore the optimal heart rate control target for septic patients and using this target as the exposure factor. The primary outcome was 28-day mortality, and the secondary outcome were ICU and in-hospital mortality. For the original cohort, we applied the log-rank test to infer the relationship between heart rate and mortality. To control for bias introduced by confounders, we utilized propensity score matching (PSM) to reduce imbalances between normal TWA-HR and high TWA-HR groups, and we established a series of models [the multivariable Cox model, matching weight (MW)-adjusted Cox model, multivariable logistic regression, MW-adjusted logistic regression, and doubly robust model] as sensitivity analyses and subgroup analyses to demonstrate the robustness of our findings. Results: A total of 13492 patients were included in our study. The RCS analysis based on Cox and logistic regression showed increased risk of mortality (P < 0.001, non-linear P < 0.001) when TWA-HR > 85 beats per minute (bpm). The log-rank test revealed in terms of the 28-day mortality, the hazard ratio (HR) (95% confidence interval [CI]) was 1.92 (1.78—2.06, P < 0.001) for patients with high TWA-HR compared to normal TWA-HR group. Similarly, for the ICU mortality, the HR (95% CI) was 1.64 (1.52—1.78, P < 0.001), and for the in-hospital mortality, the HR (95% CI) was 1.61 (1.48—1.76, P < 0.001). Collectively, the sensitivity analysis consistently demonstrated higher 28-day mortality, ICU mortality, and in-hospital mortality in patients with TWA-HR > 85 bpm. Conclusion: Patients with septic shock whose heart rate was controlled no more than 85 bpm during ICU stay received survival benefit in terms of 28-day, ICU and in-hospital mortality. [ABSTRACT FROM AUTHOR]

Sepsis and septic shock are frequent and severe clinical pictures in intensive care medicine that result from a dysregulated immune response to an infection and cause a high mortality rate. This article provides an overview of the various extracorporeal procedures used to treat sepsis. Various procedures are used to treat sepsis and septic shock. These include high-volume hemofiltration (HVHF), very high-volume hemofiltration (VHVHF), high cut-off filter (HCO), polymyxin B hemoperfusion and cytokine adsorption filters. The HVHF and VHVHF remove inflammatory mediators but show no significant benefit in terms of stabilization and survival in sepsis patients. The HCO filters effectively eliminate cytokines but so far there is no evidence of a survival benefit. Polymyxin B hemoperfusion shows promising results in initial studies in certain patient groups, while evidence for cytokine adsorption filters is limited. Combined plasma filtration and adsorption (CPFA) and therapeutic plasma exchange (TPE) have so far shown promising results in small studies. Although CPFA shows no survival benefit, TPE may have protective effects on the vascular glycocalyx. Extracorporeal procedures carry risks such as thrombosis and loss of proteins and clotting factors. The therapeutic benefit of these procedures in the treatment of sepsis remains unclear and further prospective randomized multicenter studies are needed to evaluate their efficacy and safety. There are currently no guideline recommendations for the routine use of these procedures in sepsis. [ABSTRACT FROM AUTHOR]

Background: There is a critical need for a rapid and sensitive pathogen detection method for septic patients. This study aimed to investigate the diagnostic efficacy of Digital droplet polymerase chain reaction (ddPCR) in identifying pathogens among suspected septic patients. Methods: We conducted a prospective pilot diagnostic study to clinically validate the multiplex ddPCR panel in diagnosing suspected septic patients. A total of 100 sepsis episodes of 89 patients were included in the study. Results: In comparison to blood culture, the ddPCR panel exhibited an overall sensitivity of 75.0% and a specificity of 69.7%, ddPCR yielded an additional detection rate of 17.0% for sepsis cases overall, with a turnaround time of 2.5 h. The sensitivity of ddPCR in the empirical antibiotic treatment and the non-empirical antibiotic treatment group were 78.6% versus 80.0% (p > 0.05). Antimicrobial resistance genes were identified in a total of 13 samples. Whenever ddPCR detected the genes beta-lactamase-Klebsiella pneumoniae carbapenemase (blaKPC) or beta-lactamase-New Delhi metallo (blaNDM), these findings corresponded to the cultivation of carbapenem-resistant gram-negative bacteria. Dynamic ddPCR monitoring revealed a consistent alignment between the quantitative ddPCR results and the trends observed in C-reactive protein and procalcitonin levels. Conclusions: Compared to blood culture, ddPCR exhibited higher sensitivity for pathogen diagnosis in suspected septic patients, and it provided pathogen and drug resistance information in a shorter time. The quantitative results of ddPCR generally aligned with the trends seen in C-reactive protein and procalcitonin levels, indicating that ddPCR can serve as a dynamic monitoring tool for pathogen load in septic patients. [ABSTRACT FROM AUTHOR]

Objective: Sepsis can have severe implications on lung function, leading to acute lung injury (ALI), a major contributor to sepsis-related mortality. Anisodamine hydrobromide (Ani HBr), a bioactive constituent derived from the root of Scopolia tangutica Maxim, a plant endemic to China, has demonstrated efficacy in treating septic shock. We aim to explore whether Ani HBr can alleviate sepsis-triggered ALI and elucidate the fundamental mechanisms involved. Materials and method: The protective effects of Ani HBr were assessed in two models: in vitro, lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and in vivo, cecal ligation puncture (CLP)-induced sepsis. To measure the cell viability of RAW264.7 cells after Ani HBr treatment, we used the CCK-8 assay. We quantified the levels of pro-inflammatory cytokines expression using ELISA. We also measured the expression of pyrotosis indicators by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence. Results: Our study demonstrates that Ani HBr can alleviate pulmonary edema, bleeding, and excessive inflammation induced by CLP. Additionally, it exhibits protective effects against cytotoxicity induced by LPS in RAW264.7 macrophage cells. Furthermore, Ani HBr downregulates the mRNA and protein levels of NLRP3, Caspase-1, GSDMD, IL-18, and IL-1β in both animal models and cell cultures, thereby inhibiting pyroptosis in a similar mechanism to AC-YVAD-CMK (AYC)'s blockade of Caspase-1. Moreover, Ani HBr suppresses the production and release of proinflammatory cytokines. Conclusion: These findings suggest that Ani HBr could serve as a protective agent against sepsis-induced ALI by suppressing pyroptosis. [ABSTRACT FROM AUTHOR]

Sepsis-induced myocardial dysfunction (SIMD), also known as sepsis-induced cardiomyopathy (SICM), is linked to significantly increased mortality. Despite its clinical importance, effective therapies for SIMD remain elusive, largely due to an incomplete understanding of its pathogenesis. Over the past five decades, research involving both animal models and human studies has highlighted several pathogenic mechanisms of SICM, yet many aspects remain unexplored. Initially thought to be primarily driven by inflammatory cytokines, current research indicates that these alone are insufficient for the development of cardiac dysfunction. Recent studies have brought attention to additional mechanisms, including excessive nitric oxide production, mitochondrial dysfunction, and disturbances in calcium homeostasis, as contributing factors in SICM. Emerging clinical evidence has highlighted the significant role of myocardial edema in the pathogenesis of SICM, particularly its association with cardiac remodeling in septic shock patients. This review synthesizes our current understanding of SIMD/SICM, focusing on myocardial edema's contribution to cardiac dysfunction and the critical role of the bradykinin receptor B1 (B1R) in altering myocardial microvascular permeability, a potential key player in myocardial edema development during sepsis. Additionally, this review briefly summarizes existing therapeutic strategies and their challenges and explores future research directions. It emphasizes the need for a deeper understanding of SICM to develop more effective treatments. [ABSTRACT FROM AUTHOR]

To estimate risk factors for acute kidney injury (AKI) and the effect of AKI on mortality in Staphylococcus aureus bacteraemia, while taking into account recurrent AKI episodes, competing risks, time-varying variables, and time-varying effects. We performed an unplanned analysis using data from a multicentre cohort study of patients with Staphylococcus aureus bacteraemia (SAB). The primary outcome was cumulative incidence of AKI, according to Kidney Disease Improving Global Outcomes definitions. We included 453 patients in this study of whom 194 (43%) patients experienced one or more AKI episodes. Age (hazard ratio (HR) 1.013, 95% CI 1.001–1.024), Charlson comorbidity index (HR 1.07, 95% CI 1.01–1.14), prior chronic kidney disease (HR 1.76, 95% CI 1.28–2.42), septic shock (HR 3.28, 95% CI 2.31–4.66), persistent bacteraemia (HR 1.53, 95% CI 1.08–2.17), and vancomycin therapy (HR 1.80, 95% CI 1.05–3.09) were independently associated with AKI, but flucloxacillin, cefazolin, rifampicin, and aminoglycoside therapy were not. After adjustment for confounders and immortal time bias, AKI was associated with an increased risk of 90-day mortality (HR 4.26, 95% CI 2.91–6.23). The incidence of AKI in SAB is high and a substantial proportion of patients develop recurrent episodes of AKI after recovery. AKI is specifically linked to the use of vancomycin and not to anti-staphylococcal penicillins. The clinical outcome of patients with SAB complicated by AKI is worse than previously estimated. [ABSTRACT FROM AUTHOR]

• The death group exhibits higher APACHE II/SOFA scores and LYM/CRP/Scr levels. • The death group shows higher SII/PCT levels than the survival group. • SII/PCT positively correlate with APACHE II/SOFA scores and LYM/CRP/Scr levels. • SII/PCT are independent risk factors for poor prognosis in septic shock patients. • The SII-PCT combination helps predict the poor prognosis of septic shock patients. Septic shock is the most serious complication of sepsis, with more secure and efficient biomarkers urgently needed. Systemic immune-inflammation index (SII) and serum procalcitonin (PCT) show involvement in predicting septic shock prognosis. Herein, we explored the clinical value of the SII-PCT combination in the short-term prognosis of septic shock patients. Totally 200 septic shock patients were analyzed retrospectively and allocated into the survival and death groups upon 28-day in-hospital outcomes. Correlations of SII, PCT, acute physiology and chronic health evaluation II (APACHE II)/sepsis-related organ failure assessment (SOFA) scores, C-reactive protein (CRP), and serum creatinine (Scr) were analyzed using Spearman. The influencing factors of SII and serum PCT for short-term poor prognosis were analyzed using logistic multivariate regression model. The auxiliary predictive value of SII, PCT, and their combination for short-term adverse septic shock prognosis was evaluated by the receiver operating characteristic curve. Differences in the area under the curve (AUC) were compared using MedCalc. The death group had higher APACHE II/SOFA scores, LYM, CRP, Scr, SII, and PCT levels than the survival group. SII and PCT were positively correlated with APACHE II and SOFA scores, LYM, CRP, and Scr, and were independent risk factors influencing the adverse septic shock prognosis. The AUC of the SII-PCT combination in predicting short-term adverse septic shock prognosis was 0.893 (0.841-0.932), with 76.12% sensitivity and 87.97% specificity, with the combination showing a higher AUC than SII/PCT alone. The SII-PCT combination helps predict the adverse prognosis of septic shock patients. [ABSTRACT FROM AUTHOR]

Data comparing the clinical outcomes of novel β-lactam-β-lactamase inhibitors given in combination versus monotherapy for the treatment of multidrug-resistant (MDR) P. aeruginosa infections are lacking. This retrospective cohort study included patients who received novel β-lactam–β-lactamase inhibitors as monotherapy or in combination for the treatment of MDR P. aeruginosa infections. The study was conducted between 2017 and 2022 in 6 tertiary care hospitals in Saudi Arabia. Overall in-hospital mortality, 30-day mortality, clinical cure, and acute kidney injury (AKI) were compared between recipients of monotherapy versus combination using multivariate logistic regression analysis. 118 patients and 82 patients were included in monotherapy and combination therapy arms, respectively. The cohort represented an ill population with 56% in the intensive care unit and 37% in septic shock. A total of 19% of patients presented with bacteremia. Compared to monotherapy, combination therapy did not significantly differ in clinical cure (57% vs. 68%; P = 0.313; OR, 0.63; 95% CI, 0.36–1.14) in-hospital mortality (45% vs. 37%; P = 0.267; OR, 1.38; 95% CI, 0.78–2.45), or 30-day mortality (27% vs. 24%; P = 0.619; OR, 1.18; 95% CI, 0.62–1.25). However, AKI (32% vs. 12%; P = 0.0006; OR, 3.45; 95% CI, 1.67–7.13) was significantly more common in patients who received combination therapy. Novel β-lactam–β-lactamase inhibitors when used in combination with other antibiotics did not add clinical benefit compared to their use as monotherapy in the treatment of MDR P. aeruginosa infections. A Combination regimen was associated with an increased risk of nephrotoxicity. [ABSTRACT FROM AUTHOR]

Sepsis is responsible for tremendous morbidity, mortality, and healthcare expenditure worldwide. Over the past decade, the conceptualization of sepsis has shifted from one based upon an inflammatory response to one defined by a dysregulated immune response to infection and resulting organ dysfunction. The definitions of sepsis and septic shock were revised to improve their diagnostic specificity and facilitate accurate and timely diagnoses at the bedside. The core of sepsis management remains early identification and diagnostic testing, early antimicrobial therapy, and early haemodynamic resuscitation. Recently, there has been additional movement towards classifying and treating sepsis based on genotype, phenotype, and endotype, though these methods are not yet widely accessible or adopted. Current guidelines recommend that the first steps in treatment and resuscitation take place within 1 hour from when septic shock is suspected. Additional essential elements in the current sepsis management guidelines include using dynamic parameters to assess fluid responsiveness, a conservative fluid strategy following initial resuscitation (with subsequent de-resuscitation when possible), serial reassessments of haemodynamic status, and adaptable treatment plans. This review provides a summary of the most recent clinical trials and practice guidelines for the diagnosis and treatment of sepsis in the critical care setting. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sepsis, a leading global health challenge, accounts for around 20% of deaths worldwide. The complexity of sepsis, especially the difference between bacterial and viral etiologies, requires an effective assessment of microcirculation during resuscitation. This study aimed to evaluate the impact of infusion therapy on microcirculation in patients with sepsis, focusing on bacterial- and COVID-19-associated sepsis using remote photoplethysmography (rPPG) and the automated capillary refill time (aCRT). Materials and Methods: This single-center prospective study was conducted in the ICU of Pauls Stradins Clinical University Hospital, including 20 patients with sepsis/septic shock. The patients were selected based on hemodynamic instability and divided into COVID-19 and Bacterial Septic Shock groups. Fluid responsiveness was assessed using the Passive Leg Raising Test (PLRT). Systemic hemodynamics and microcirculation were monitored through MAP CRT, rPPG, and serum lactate levels. Statistical analyses compared responses within and between the groups across different stages of the protocol. Results: The Bacterial group exhibited higher initial serum lactate levels and more pronounced microcirculatory dysfunction than the COVID-19 group. rPPG was more sensitive in detecting perfusion changes, showing significant differences between the groups. The automated CRT demonstrated greater sensitivity compared to the manual CRT, revealing significant differences during PLRT stages between bacterial- and COVID-19-associated sepsis. Both groups had a transient hemodynamic response to PLRT, with subsequent stabilization upon fluid infusion. Conclusions: When managing patients with sepsis in intensive care, monitoring microcirculation is of paramount importance in infusion therapy. Our study highlights the potential of rPPG and aCRT as tools for this purpose. These techniques can be used in conjunction with routine parameters, such as lactate levels and systemic hemodynamic parameters, to provide a comprehensive assessment of a patient's condition. [ABSTRACT FROM AUTHOR]

Background and Objectives: The predictive value of changes in C-reactive protein (CRP), procalcitonin, and leukocyte levels, which are commonly used in the diagnosis of infection in sepsis and septic shock, remains a topic of debate. The aim of this study was to evaluate the effectiveness of changes in CRP, procalcitonin, and leukocyte counts on the prognosis of 230 patients admitted to the intensive care unit (ICU) with the diagnosis of sepsis and pneumonia-related septic shock between 1 April 2022 and 31 December 2023, and to investigate whether any of these markers have a superior predictive value over the others in forecasting prognosis. Materials and Methods: This single-center, retrospective, cross-sectional observational study included patients who developed sepsis and septic shock due to community-acquired pneumonia and were admitted to the ICU. Demographic data, 1-month and 90-day mortality rates, length of stay in the ICU, discharge to the ward or an outside facility, need for dialysis after sepsis, need for invasive or noninvasive mechanical ventilation during the ICU stay and the duration of this support, whether patients admitted with sepsis or septic shock required inotropic agent support during their stay in the ICU and whether they received monotherapy or combination therapy with antibiotics during their admission to the ICU, the Comorbidity Index score (CCIS), CURB-65 score (confusion, uremia, respiratory rate, BP, age ≥ 65), and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score were analyzed. Additionally, CRP, procalcitonin, and leukocyte levels were recorded, and univariate and multivariate logistic regression analyses were performed to evaluate their effects on 1- and 3-month mortality outcomes. In all statistical analyses, a p-value of <0.05 was accepted as a significant level. Results: According to multivariate logistic regression analysis, low BMI, male gender, and high CCIS, CURB-65, and APACHE-II scores were found to be significantly associated with both 1-month and 3-month mortality (p < 0.05). Although there was no significant relationship between the first-day levels of leukocytes, CRP, and PCT and mortality, their levels on the third day were observed to be at their highest in both the 1-month and 3-month mortality cases (p < 0.05). Additionally, a concurrent increase in any two or all three of CRP, PCT, and leukocyte values was found to be higher in patients with 3-month mortality compared with those who survived (p = 0.004). Conclusions: In patients with pneumoseptic or pneumonia-related septic shock, the persistent elevation and concurrent increase in PCT, CRP, and leukocyte values, along with male gender, advanced age, low BMI, and high CCIS, CURB-65, and APACHE-II scores, were found to be significantly associated with 3-month mortality. [ABSTRACT FROM AUTHOR]

Introduction: α-galactosylceramide (α-GalCer), a prototypical agonist of invariant natural killer T (iNKT) cells, stimulates iNKT cells to produce various cytokines such as IFNγ and IL4. Moreover, repeated α-GalCer treatment can cause protective or pathogenic outcomes in various immune-mediated diseases. However, the precise role of α-GalCer-activated iNKT cells in sepsis development remains unclear. To address this issue, we employed a lipopolysaccharide (LPS)/D- galactosamine (D-GalN)-induced murine sepsis model and two alternative models. Methods: Sepsis was induced in wild-type (WT) C57BL/6 (B6) mice by three methods (LPS/D-GalN, α-GalCer/D-GalN, and cecal slurry), and these mice were monitored for survival rates. WT B6 mice were intraperitoneally injected with α-GalCer or OCH (an IL4-biased α-GalCer analog) one week prior to the induction of sepsis. To investigate the effects of α-GalCer-mediated iNKT cell activation on sepsis development, immune responses were analyzed by flow cytometry using splenocytes and liver-infiltrating leukocytes. In addition, a STAT6 inhibitor (AS1517499) and an IL10 inhibitor (AS101) were employed to evaluate the involvement of IL4 or IL10 signaling. Furthermore, we performed B cell adoptive transfers to examine the contribution of α-GalCer-induced regulatory B (Breg) cell populations in sepsis protection. Results: In vivo α-GalCer pretreatment polarized iNKT cells towards IL4- and IL10-producing phenotypes, significantly attenuating LPS/D-GalN-induced septic lethality in WT B6 mice. Furthermore, α-GalCer pretreatment reduced the infiltration of immune cells to the liver and attenuated pro-inflammatory cytokine production. Treatment with a STAT6 inhibitor was unable to modulate disease progression, indicating that IL4 signaling did not significantly affect iNKT cell-mediated protection against sepsis. This finding was confirmed by pretreatment with OCH, which did not alter sepsis outcomes. However, interestingly, prophylactic effects of α-GalCer on sepsis were significantly suppressed by treatment with an IL10 antagonist, suggesting induction of IL10-dependent anti-inflammatory responses. In addition to IL10-producing iNKT cells, IL10-producing B cell populations were significantly increased after α-GalCer pretreatment. Conclusion: Overall, our results identify α-GalCer-mediated induction of IL10 by iNKT and B cells as a promising option for controlling the pathogenesis of postoperative sepsis. [ABSTRACT FROM AUTHOR]

Background Septic melioidosis is associated with high mortality in resource-limited settings. The current study aims to find 28-d all-cause mortality predictors within 24 h of admission in melioidosis patients presenting to an emergency department. Methods This retrospective cohort study (2018–2022) included melioidosis patients divided into two groups based on their primary outcomes (28-d mortality). All the clinically relevant factors significant in univariate analysis were selected for binary logistic regression analysis. Those factors significant in logistic regression analysis were considered independent predictors of mortality. Results Of the 53 patients with melioidosis, the 28-d mortality of melioidosis patients admitted to the emergency department was 51% (n=27). Respiratory involvement, renal dysfunction, haemodynamic instability, elevated aspartate transaminase, elevated activated partial thromboplastin time, elevated CRP, elevated procalcitonin, decreased albumin, decreased absolute neutrophil count, decreased absolute lymphocyte count and use of piperacillin-tazobactam or azithromycin were significant predictors of mortality on univariate analysis. Vasopressor requirement (p=0.03) and low serum albumin level (0.041) at presentation were independent predictors of mortality. Conclusion Vasopressor requirement and low albumin levels at presentation in the emergency department are independent predictors of mortality. There is a need to create awareness among primary care physicians to enable early diagnosis and prompt initiation of treatment. [ABSTRACT FROM AUTHOR]

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Background: The appropriate third-line vasopressor in septic shock patients receiving norepinephrine and vasopressin is unknown. Angiotensin-II (AT-II) offers a unique mechanism of action to traditionally used vasopressors in septic shock. Objective: The objective of this study was to compare the clinical efficacy and safety of third-line AT-II to epinephrine in patients with septic shock. Methods: A single-center, retrospective cohort study of critically ill patients was performed between April 1, 2019 and July 31, 2022. Propensity-matched (2:1) analysis compared adults with septic shock who received third-line AT-II to controls who received epinephrine following norepinephrine and vasopressin. The primary outcome was clinical response 24 hours after third-line vasopressor initiation. Additional efficacy and safety outcomes were investigated. Results: Twenty-three AT-II patients were compared with 46 epinephrine patients. 47.8% of AT-II patients observed a clinical response at hour 24 compared with 28.3% of epinephrine patients (P = 0.12). In-hospital mortality (65.2% vs 73.9%, P = 0.45), cardiac arrhythmias (26.1% vs 26.1%, P = 0.21), and thromboembolism (4.3% vs 2.2%, P = 0.61) were not observed to be statistically different between groups. Conclusions and relevance: Administration of AT-II as a third-line vasopressor agent in septic shock patients was not associated with significantly improved clinical response at hour 24 compared with epinephrine. Although underpowered to detect meaningful differences, the clinical observations of this study warrant consideration and further investigation of AT-II as a third-line vasopressor in septic shock. [ABSTRACT FROM AUTHOR]