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Background : Previous studies have reported the fundamental role of immunoregulatory proteins in the clinical phenotype and outcome of sepsis. This study investigated two functional single nucleotide polymorphisms (SNPs) of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), which has a negative stimulatory function in the T cell immune response. Methods : Patients with sepsis ( n = 712) were prospectively enrolled from three intensive care units (ICUs) at the University Medical Center Goettingen since 2012. All patients were genotyped for the TIM-3 SNPs rs1036199 and rs10515746. The primary outcome was 28-day mortality. Disease severity and microbiological findings were secondary endpoints. Results : Kaplan-Meier survival analysis demonstrated a significantly lower 28-day mortality for TIM-3 rs1036199 AA homozygous patients compared to C-allele carriers (18% vs. 27%, p = 0.0099) and TIM-3 rs10515746 CC homozygous patients compared to A-allele carriers (18% vs. 26%, p = 0.0202). The TIM-3 rs1036199 AA genotype and rs10515746 CC genotype remained significant predictors for 28-day mortality in the multivariate Cox regression analysis after adjustment for relevant confounders (adjusted hazard ratios: 0.67 and 0.70). Additionally, patients carrying the rs1036199 AA genotype presented more Gram-positive and Staphylococcus epidermidis infections, and rs10515746 CC homozygotes presented more Staphylococcus epidermidis infections. Conclusion : The studied TIM-3 genetic variants are associated with altered 28-day mortality and susceptibility to Gram-positive infections in sepsis.

Objective: The mortality associated with sepsis remains unacceptably high, despite modern high-quality intensive care. Based on the results from previous studies, anaemia and its management in patients with sepsis appear to impact outcomes; however, the transfusion policy is still being debated, and the ideal approach may be extremely specific to the individual. This study aimed to investigate the long-term impact of anaemia requiring red blood cell (RBC) transfusion on mortality and disease severity in patients with sepsis. We studied a general surgical intensive care unit (ICU) population, excluding cardiac surgery patients. 435 patients were enrolled in this observational study between 2012 and 2016., Results: Patients who received RBC transfusion between 28 days before and 28 days after the development of sepsis (n = 302) exhibited a significantly higher 90-day mortality rate (34.1% vs 19.6%; P = 0.004, Kaplan-Meier analysis). This association remained significant after adjusting for confounders in the multivariate Cox regression analysis (hazard ratio 1.68; 95% confidence interval 1.03-2.73; P = 0.035). Patients who received transfusions also showed significantly higher morbidity scores, such as SOFA scores, and ICU lengths of stay compared to patients without transfusions (n = 133). Our results indicate that anaemia and RBC transfusion are associated with unfavourable outcomes in patients with sepsis.

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a surface protein on T cells, that has an inhibitory effect on the host immune reaction and prevents overreaction of the immune system. Because the functional single-nucleotide polymorphism (SNP) rs231775 of the CTLA-4 gene is associated with autoimmune diseases and because of the critical role of the immune reaction in sepsis, we intended to examine the effect of this polymorphism on survival in patients with sepsis. 644 septic adult Caucasian patients were prospectively enrolled in this study. Patients were followed up for 90 days. Mortality risk within this period was defined as primary outcome parameter. Kaplan-Meier survival analysis revealed a significantly lower 90-day mortality risk among GG homozygous patients (n = 101) than among A allele carriers (n = 543; 22% and 32%, respectively; p = 0.03565). Furthermore, the CTLA-4 rs231775 GG genotype remained a significant covariate for 90-day mortality risk after controlling for confounders in the multivariate Cox regression analysis (hazard ratio: 0.624; 95% CI: 0.399-0.975; p = 0.03858). In conclusion, our study provides the first evidence for CTLA-4 rs231775 as a prognostic variable for the survival of patients with sepsis and emphasizes the need for further research to reveal potential functional associations between CTLA-4 and the immune pathophysiology of sepsis.

According to previous investigations, CD14 is suggested to play a pivotal role in initiating and perpetuating the pro-inflammatory response during sepsis. A functional polymorphism within the CD14 gene, rs2569190, has been shown to impact the pro-inflammatory response upon stimulation with lipopolysaccharide, a central mediator of inflammation in sepsis. In this study, we hypothesized that the strong pro-inflammatory response induced by the TT genotype of CD14 rs2569190 may have a beneficial effect on survival (30-day) in patients with sepsis. A total of 417 adult patients with sepsis (and of western European descent) were enrolled into this observational study. Blood samples were collected for rs2569190 genotyping. Patients were followed over the course of their stay in the ICU, and the 30-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure as a secondary variable. Moreover, organ support-free days were evaluated as a secondary outcome parameter. TT-homozygous patients were compared to C-allele carriers. Kaplan-Meier survival analysis revealed a higher 30-day mortality risk among C-allele carriers compared with T homozygotes (p = 0.0261). To exclude the effect of potential confounders (age, gender, BMI and type of infection) and covariates that varied at baseline with a p-value < 0.2 (e.g., comorbidities), we performed multivariate Cox regression analysis to examine the survival time. The CD14 rs2569190 C allele remained a significant covariate for the 30-day mortality risk in the multivariate analysis (hazard ratio, 2.11; 95% CI, 1.08-4.12; p = 0.0282). The 30-day mortality rate among C allele carriers was 23%, whereas the T homozygotes had a mortality rate of 13%. Additionally, an analysis of organ-specific SOFA scores revealed a significantly higher SOFA-Central nervous system score among patients carrying the C allele compared with T-homozygous patients (1.9±1.1 and 1.6±1.0, respectively; p = 0.0311). In conclusion, CD14 rs2569190 may act as a prognostic variable for the short-term outcome (30-day survival) in patients with sepsis.

According to previous studies, the clinical course of sepsis could be affected by preexisting medical conditions, which are very common among patients with sepsis. This observational study aimed at investigating whether common chronic medical conditions affect the 90-day mortality risk in adult Caucasian patients with sepsis. A total of 482 patients with sepsis were enrolled in this study. The ninety-day mortality was the primary outcome; organ failure was the secondary outcome. Sepsis-related organ failure assessment (SOFA) scores and the requirements for organ support were evaluated to assess organ failure. A multivariate Cox regression model for the association between the 90-day mortality risk and chronic preexisting medical conditions adjusted for all relevant confounders and mortality predictors revealed the highest hazard ratio for patients with chronic kidney disease (CKD) (hazard ratio, 2.25; 95% CI, 1.46-3.46; p = 0.0002). Patients with CKD had higher SOFA scores than patients without CKD (8.9 ± 4.0 and 6.5 ± 3.4, respectively; p < 0.0001). Additionally, an analysis of organ-specific SOFA scores revealed higher scores in three organ systems (kidney, cardiovascular and coagulation). Patients with CKD have the highest 90-day mortality risk compared with patients without CKD or with other chronic medical conditions.

Background: Toll-like receptor 4 (TLR4), a lipopolysaccharide (LPS) receptor complex signal-transducing molecule, plays a crucial role in sensing LPS from gram-negative bacteria. TLR4 signaling pathway activation by LPS plays a major role in sepsis pathogenesis. A single nucleotide polymorphism, rs11536889, in the 3'-untranslated region of the TLR4 gene is thought to affect TLR4 translation. This study aimed to investigate whether organ failure in sepsis patients is related to the TLR4 rs11536889 genotype., Methods: Adult Caucasian patients with sepsis from the intensive care unit of a university medical center were followed up for 90 days, and organ failure was recorded as the primary outcome variable. Blood samples were collected at enrollment for TLR4 rs11536889 genotyping. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure., Results: A total of 210 critically ill patients with sepsis were enrolled into this study. Wild-type GG was compared to GC/CC. During their stay in the intensive care unit, GG patients presented significantly higher SOFA scores than did C allele carriers (7.9 ± 4.5 and 6.8 ± 4.2, respectively; p = 0.0005). Analysis of organ-specific SOFA sub-scores revealed significant differences in three organ systems: renal, coagulation and hepatic (p = 0.0005, p = 0.0245 and p < 0.0001, respectively). Additionally, the rs11536889 polymorphism was associated with a higher incidence of gram-negative infections., Conclusions: These results offer the first evidence that TLR4 rs11536889 is a useful marker of organ failure in patients with sepsis.

Background: Sepsis is a life-threatening condition. Programmed cell death 1 protein (PD-1), a negative costimulatory molecule, is suggested to be involved in pathogenesis as mortality is associated with high expression and as neutralizing antibodies improve survival in a mouse model. The PD-1 gene harbors an intronic single-nucleotide polymorphism, rs11568821, which is located in a transcription factor-binding site and supposed to affect PD-1 transcription., Objective: This study aimed at investigating whether mortality (90-day) among patients with sepsis associates with PD-1 rs11568821 genotypes., Methods: Adult white patients with sepsis from the surgical intensive care units of a university medical center were followed up for 90 days, and mortality was recorded as primary outcome variable. Blood samples were taken for PD-1 rs11568821 genotyping. Sequential Organ Failure Assessment scores increased at enrollment and during the observation period to monitor morbidity., Results: Two hundred nineteen critically ill patients with sepsis were enrolled in this investigation. Ninety-day mortality was significantly higher among G homozygotes than among A allele carriers (P = 0.0032). During intensive care unit stay, G homozygotes experienced higher Sequential Organ Failure Assessment scores (P < 0.001) and a higher demand of vasopressor therapy (P = 0.0107)., Conclusions: Data provide first associative evidence for PD-1 rs11568821 as a prognostic indicator in patients with sepsis.

(1) Background: Patients with sepsis following surgical intervention may exhibit fundamental distinctions from those experiencing sepsis without prior surgery. Despite the potential clinical importance of distinguishing these two sepsis subpopulations, dissimilarities, particularly in outcome, between surgical and non-surgical patients have been subject to limited scientific investigations in the existing literature. This study aimed to investigate the differences in mortality and sepsis-associated organ dysfunction between these two groups. (2) Methods: A retrospective analysis was conducted using data from a large cohort of prospectively enrolled patients with sepsis (n = 737) admitted to three intensive care units at University Medical Center Goettingen; patients were categorized into surgical (n = 582) and non-surgical sepsis groups (n = 155). The primary outcomes assessed were 28- and 90-day mortality rates, and secondary endpoints were multiple clinical parameters and measures of sepsis-associated organ dysfunction. (3) Results: Non-surgical patients presented a significantly higher 90-day mortality (37%) compared to surgical sepsis patients (30%, p = 0.0457). Moreover, the non-surgical sepsis group exhibited increased sepsis-associated organ dysfunction, as evidenced by higher average SOFA scores (p < 0.001), elevated levels of serum Procalcitonin (p = 0.0102), and a higher utilization of organ replacement therapies such as ventilation (p < 0.001), vasopressor treatment (p < 0.001), and renal replacement therapy (p = 0.0364). Additionally, non-surgical sepsis patients had higher organ-specific SOFA respiratory (p < 0.001), cardiovascular (p < 0.001), renal (p < 0.001), coagulation (0.0335), and central nervous system (p = 0.0206) subscores. (4) Conclusions: These results suggested that patients with non-surgical sepsis may face distinct challenges and a higher risk of adverse outcomes compared to patients with sepsis following surgical intervention. These findings have important implications for clinical decision-making, patient management, and resource allocation in sepsis care. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances in the clinical management and understanding of sepsis and septic shock, these complex clinical syndromes continue to have high mortality rates. The effect of sex on these diseases' mortality, clinical presentation and morbidity remains controversial. This study aimed to investigate the association of sex with mortality and organ dysfunction in patients with sepsis and septic shock. Methods: Prospectively enrolled patients with clinically defined sepsis and septic shock in three intensive care units at University Medical Center Göttingen, Germany, were investigated. The primary outcomes were 28- and 90-day mortality, while the secondary endpoints included the evaluation of organ dysfunction as measured by clinical scores and laboratory parameters. Results: A total of 737 septic patients were enrolled, including 373 in septic shock, 484 males, and 253 females. No significant differences in 28- and 90-day mortality were observed in the cohort. However, men with sepsis had significantly higher SOFA scores, SOFA respiratory and renal subscores, bilirubin and creatinine values, and lower weight-adapted urine outputs, indicating higher organ dysfunction compared to women. Conclusions: Our findings revealed notable differences in organ dysfunction between male and female patients, with males exhibiting more pronounced dysfunction across multiple clinical indicators. These results highlight the potential influence of sex on sepsis disease severity and suggest the need for tailored approaches in sepsis management according to patient sex. [ABSTRACT FROM AUTHOR]