Sepsa je život ohrozujúci stav s orgánovou dysfunkciou a dysregulovanou odpoveďou organizmu na infekčné agens. Incidencia v Európe je 3,4 milióna prípadov každý rok. Mortalita je vysoká a má 2 vrcholy – u detí vo veku do 5 rokov a u seniorov. Analyzovali sme 65-ročných a starších pacientov so sepsou (n = 32). Zamerali sme sa na vzájomný vzťah kardiálnych (NT-proBNP a troponín) a renálnych (urea a kreatinín) ukazovateľov v časovom rámci prvých 72 hodín od stanovenia diagnózy sepsy. Vychádzali sme z predpokladu, že srdce a obličky nie sú dve oddelené nádoby, ale sú skôr dva kodominantné permanentne prepojené elementy. Súvislosti sme sledovali v 2 rovinách a to v rámci kardiorenálnych interakcií a pri kardiorenoinflamatórnom komplexe. Preukázal sa pozitívny vzťah medzi markermi v oboch týchto rovinách, avšak ich prepojenie nebolo fixné, ale dynamicky sa meniace, pričom ako rozhodujúci časový rámec vyšiel horizont prvých 24 hodín. To podporuje koncept kardiorenálneho syndrómu (KRS) 5. typu ako dynamického ochorenia. Hoci pribúdajú údaje o stúpajúcej incidencii latentného chronického postihnutia srdca aj obličiek, ostáva otvorená otázka, či KRS 5. typu je samostatnou nozologickou jednotkou, alebo je subtypom KRS 1. či 3. typu.

Sepsis is a life-threatening condition with organ dysfunction and dysregulated body response to infectious agents. The incidence in Europe is 3.4 million cases each year. Mortality is high and has 2 peaks – in children under the age of 5 and in the elderly. We analyzed a set of 65-years old and older pacients with sepsis (n = 32). We focused on the relationship between cardiac (NT-proBNP and troponin) and renal (urea and creatinine) indicators within the time frame of the first 72 hours after diagnosis of sepsis. We started from the assumption that the heart and kidneys are not two separate vessels, but rather two codominant permanently connected elements. We monitored relationships in 2 levels, within the cardio-renal interactions and in the cardio-reno-inflammatory complex. A positive relationship between markers in both levels was demonstrated, but their connection was not fixed, but dynamically changing, with the first 24 hours being the decisive time frame. This supports the concept of cardio-renal syndrome(KRS) type 5 as a dynamic disease. Due to the increasing data on the rising incidence of latent chronic involvement of the heart and kidneys, the question is whether CRS type 5 is a separate nosological unit or is a subtype of CRS type 1 or 3.

• MeSH
• Analysis of Variance MeSH
• Biomarkers blood   MeSH
• Time Factors MeSH
• Cardio-Renal Syndrome diagnosis   blood   MeSH
• Clinical Laboratory Techniques methods   instrumentation   MeSH
• Humans MeSH
• Renal Insufficiency diagnosis   blood   MeSH
• Aged MeSH
• Sepsis * complications   MeSH
• Heart Failure * diagnosis   blood   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Clinical Study MeSH

OBJECTIVE: Pelvic exenteration is a radical surgery for advanced or recurrent pelvic tumors, requiring careful patient selection and a multi-disciplinary approach. Despite advancements, it remains high-risk, with limited data on outcomes. The present meta-analysis evaluates survival, mortality, and trends to clarify its role in gynecologic oncology. METHODS: A systematic search was conducted in January 2025 to identify studies on pelvic exenteration outcomes for gynecologic malignancies. Studies with at least 10 patients reporting 5-year overall survival or 30-day mortality were included. Data extracted included patient and surgical characteristics, and a scoring system based on study design, sample size, and center volume was used to include high-quality studies (score ≥3). Poisson regression models were used to analyze the associations between predictors and outcomes, with results expressed as incidence rate ratios and a 95% CI. RESULTS: A total of 46 studies involving 4417 patients met the inclusion criteria. Most patients underwent pelvic exenteration for cervical cancer (N = 3183). Positive pelvic and aortic nodal involvement were key predictors of reduced 5-year overall survival, decreasing by 3.9% and 5.9% per 1% increase in nodal positivity, respectively. Pelvic wall involvement also significantly reduced survival by 15.9%. The 30-day mortality rate was 5.1%, with sepsis (27.2%) being the leading cause of death. Peri-operative mortality decreased significantly over time, with each year of publication associated with a 2.6% decrease in incidence rate. However, pelvic sidewall involvement and total exenteration increased 30-day mortality by 11.5% and 0.7%, respectively. CONCLUSIONS: Pelvic exenteration remains a viable but high-risk option for select patients with advanced gynecologic malignancies. Pre-operative assessment and multi-disciplinary planning are essential for optimizing outcomes.

• MeSH
• Pelvic Exenteration * mortality   methods   MeSH
• Humans MeSH
• Genital Neoplasms, Female * surgery   mortality   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) for COVID-19 was thoroughly assessed during the first pandemic wave, but data on subsequent waves are limited. We aimed to investigate in-hospital and 6-month survival of patients with COVID-19 supported with ECMO from the second pandemic wave (Sept 15, 2020) until the end of the pandemic (March 21, 2023, announced by WHO). METHODS: EuroECMO-COVID is a prospective, observational study including adults (aged ≥16 years) requiring ECMO respiratory support for COVID-19 from 98 centres in 21 countries. We compared patient characteristics and outcomes between in-hospital survivors and non-survivors. Mixed-effects multivariable logistic regressions were used to investigate factors linked to in-hospital mortality. 6-month survival and overall patient status were determined via patient contact or chart review. This study is registered with ClinicalTrials.gov, NCT04366921, and is complete. FINDINGS: We included 3860 patients (2687 [69·7%] were male and 1169 [30·3%] were female; median age 51 years [SD 11]) from 98 centres in 21 countries. In-hospital mortality was 55·9% (n=2158), with 81·2% (n=1752) deaths occurring during ECMO support. More non-survivors had diabetes, hypertension, cardiovascular disease, and renal failure, and required more pre-ECMO inotropes and vasopressors compared with survivors. Median support duration was 18 days (IQR 10-31) for both groups. Factors linked to in-hospital mortality included older age, pre-ECMO renal failure, pre-ECMO vasopressors use, longer time from intubation to ECMO initiation, and complications, including neurological events, sepsis, bowel ischaemia, renal failure, and bleeding. Of the 1702 (44·1%) in-hospital survivors, 99·7% (n=1697) were alive at 6 months follow-up. Many patients at 6 months follow-up had dyspnoea (501 [32·0%] of 1568 patients), cardiac (122 [7·8%] of 1568 patients), or neurocognitive (168 [10·7%] of 1567 patients) symptoms. INTERPRETATION: Our data for patients undergoing ECMO support for respiratory distress from the second COVID-19 wave onwards confirmed most findings from the first wave regarding patient characteristics and factors correlated to in-hospital mortality. Nevertheless, in-hospital mortality was higher than during the initial pandemic wave while 6-month post-discharge survival remained favourable (99·7%). Persisting post-discharge symptoms confirmed the need for post-ECMO patient follow-up programmes. FUNDING: None.

• MeSH
• COVID-19 * therapy   mortality   epidemiology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Extracorporeal Membrane Oxygenation * methods   MeSH
• Hospital Mortality MeSH
• Follow-Up Studies MeSH
• Prospective Studies MeSH
• SARS-CoV-2 MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH

BACKGROUND: Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea. METHODS: Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea. We will exclude patients with ongoing sepsis, need of systemic antibiotics, or those after recent bowel surgery or any other reason that prevents the FMT. Randomisation will be in 1:1 ratio. Patients in the control group will receive standard treatment based on oral diosmectite. In the intervention group, patients will receive, in addition to the standard of care, faecal microbiota transplantation via rectal tube, in the form of a preparation mixed from 7 thawed aliquots (50 mL) made from fresh stool of 7 healthy unrelated donors and quarantined deep frozen for 3 to 12 months. Primary outcome is treatment failure defined as intervention not delivered or diarrhoea persisting at day 7 after randomisation. Secondary outcomes include safety measures such as systemic inflammatory response, adverse events, and also diarrhoea recurrence within 28 days. Exploratory outcomes focus on gut barrier function and composition of intestinal microbiota. DISCUSSION: Faecal microbiota transplantation has been effective for dysbiosis in non-critically ill patients with recurrent C. difficile infections and it is plausible to hypothesize that it will be equally effective for symptoms of dysbiosis in the critically ill patients. In addition, animal experiments and observational data suggest other benefits such as reduced colonization with multi-drug resistant bacteria and improved gut barrier and immune function. The frozen faeces from unrelated donors are immediately available when needed, unlike those from the relatives, who require lengthy investigation. Using multiple donors maximises graft microbiota diversity. Nonetheless, in vulnerable critically ill patients, Faecal microbiota transplantation might lead to bacterial translocation and unforeseen complications. From growing number of case series it is clear that its off label use in the critically ill patients is increasing and that there is a burning need to objectively assess its efficacy and safety, which this trial aims. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT05430269).

• MeSH
• Anti-Bacterial Agents * adverse effects   therapeutic use   MeSH
• Dysbiosis therapy   microbiology   MeSH
• Feces microbiology   MeSH
• Fecal Microbiota Transplantation * methods   adverse effects   MeSH
• Clinical Trials, Phase II as Topic MeSH
• Critical Illness * MeSH
• Humans MeSH
• Multicenter Studies as Topic MeSH
• Prospective Studies MeSH
• Diarrhea * therapy   microbiology   MeSH
• Randomized Controlled Trials as Topic MeSH
• Gastrointestinal Microbiome * drug effects   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH

Linoleic acid (LA), an essential fatty acid, has emerged as a pivotal regulator in disorders associated with inflammation in recent years; however, the underlying mechanisms are still not completely understood. We utilized network pharmacology and experimental methodologies to elucidate the mechanisms underlying the anti-inflammatory effects of LA. Our network pharmacology analysis revealed that LA shares common targets with sepsis. These targets are enriched in various pathways comprising C-type signaling pathway, PI3K-Akt signaling pathway, toll-like receptor signaling pathway, neutrophil extracellular trap formation, AMPK signaling pathway, and autophagy-animal. These findings suggest that LA may exert regulatory effects on inflammation and autophagy during sepsis. Subsequently, we established in vivo and ex vivo models of sepsis using lipopolysaccharide (LPS) in experimental study. Treatment with LA reduced lung damage in mice with LPS-induced lung injury, and reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma, bronchoalveolar lavage fluid (BALF), and peritoneal lavage fluid (PLF). LA also decreased the production of TNF-α and IL-6 in RAW264.7 macrophages exposed to LPS. In LPS-induced RAW264.7 macrophages, LA induced an elevation in LC3-II while causing a reduction in p62, which was associated with downregulation of toll-like receptor 4 (TLR4). We utilized 3-methyladenine (3-MA) to inhibit the autophagic activity, which reversed the modulatory effects of LA on LC3-II and p62. 3-MA also prevented the decline in TLR4 expression along with reduction in pro-inflammatory cytokines secretion. Our findings suggest that the activation of autophagy by LA may lead to the downregulation of TLR4, thereby exerting its anti-inflammatory effects.

• MeSH
• Autophagy * drug effects   MeSH
• Linoleic Acid * pharmacology   MeSH
• Lipopolysaccharides * toxicity   MeSH
• Macrophages * drug effects   metabolism   immunology   MeSH
• Mice MeSH
• RAW 264.7 Cells MeSH
• Sepsis chemically induced   drug therapy   metabolism   immunology   MeSH
• Signal Transduction drug effects   MeSH
• Toll-Like Receptor 4 * metabolism   MeSH
• Inflammation * metabolism   drug therapy   chemically induced   pathology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

OBJECTIVES: Most post-cardiotomy (PC) extracorporeal membrane oxygenation (ECMO) runs last less than 7 days. Studies on the outcomes of longer runs have provided conflicting results. This study investigates patient characteristics and short- and long-term outcomes in relation to PC ECMO duration, with a focus on prolonged (> 7 d) ECMO. DESIGN: Retrospective observational cohort study. SETTING: Thirty-four centers from 16 countries between January 2000 and December 2020. PATIENTS: Adults requiring post PC ECMO between 2000 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Characteristics, in-hospital, and post-discharge outcomes were compared among patients categorized by ECMO duration. Survivors and nonsurvivors were compared in the subgroup of patients with ECMO duration greater than 7 days. The primary outcome was in-hospital mortality. Two thousand twenty-one patients were included who required PC ECMO for 0-3 days ( n = 649 [32.1%]), 4-7 days ( n = 776 [38.3%]), 8-10 days ( n = 263 [13.0%]), and greater than 10 days ( n = 333 [16.5%]). There were no major differences in the investigated preoperative and procedural characteristics among ECMO duration groups. However, the longer ECMO duration category was associated with multiple complications including bleeding, acute kidney injury, arrhythmias, and sepsis. Hospital mortality followed a U-shape curve, with lowest mortality in patients with ECMO duration of 4-7 days ( n = 394, 50.8%) and highest in patients with greater than 10 days ECMO support ( n = 242, 72.7%). There was no significant difference in post-discharge survival between ECMO duration groups. In patients with ECMO duration greater than 7 days, age, comorbidities, valvular diseases, and complex procedures were associated with nonsurvival. CONCLUSIONS: Nearly 30% of PC ECMO patients were supported for greater than 7 days. In-hospital mortality increased after 7 days of support, especially in patients undergoing valvular and complex surgery, or who had complications, although the long-term post-discharge prognosis was comparable to PC ECMO patients with shorter support duration.

• MeSH
• Time Factors MeSH
• Cardiac Surgical Procedures * adverse effects   mortality   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Extracorporeal Membrane Oxygenation * methods   adverse effects   MeSH
• Hospital Mortality * MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH

OBJECTIVES: The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. DESIGN: Prospective randomized large-animal peritoneal septic shock experiment. SETTING: Laboratory investigation. SUBJECTS: Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 μg/kg/min (LATE, n = 8). INTERVENTIONS: Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. CONCLUSIONS: In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.

• Publication type
• Journal Article MeSH

PURPOSE: The aim of this study was to examine the effects of intravenous (IV) fluid restriction on time to resolution of hyperlactatemia in septic shock. Hyperlactatemia in sepsis is associated with worse outcome. Sepsis guidelines suggest targeting lactate clearance to guide fluid therapy despite the complexity of hyperlactatemia and the potential harm of fluid overload. METHODS: We conducted a post hoc analysis of serial plasma lactate concentrations in a sub-cohort of 777 patients from the international multicenter clinical CLASSIC trial (restriction of intravenous fluids in intensive care unit (ICU) patients with septic shock). Adult ICU patients with septic shock had been randomized to restrictive (n = 385) or standard (n = 392) intravenous fluid therapy. The primary outcome, time to resolution of hyperlactatemia, was analyzed with a competing-risks regression model. Death and discharge were competing outcomes, and administrative censoring was imposed 72 h after randomization if hyperlactatemia persisted. The regression analysis was adjusted for the same stratification variables and covariates as in the original CLASSIC trial analysis. RESULTS: The hazard ratios (HRs) for the cumulative probability of resolution of hyperlactatemia, in the restrictive vs the standard group, in the unadjusted analysis, with time split, were 0.94 (confidence interval (CI) 0.78-1.14) at day 1 and 1.21 (0.89-1.65) at day 2-3. The adjusted analyses were consistent with the unadjusted results. CONCLUSION: In this post hoc retrospective analysis of a multicenter randomized controlled trial (RCT), a restrictive intravenous fluid strategy did not seem to affect the time to resolution of hyperlactatemia in adult ICU patients with septic shock.

• MeSH
• Time Factors MeSH
• Hyperlactatemia * etiology   MeSH
• Intensive Care Units * statistics & numerical data   MeSH
• Lactic Acid blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Shock, Septic * therapy   complications   blood   mortality   MeSH
• Fluid Therapy * methods   standards   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

BACKGROUND: Prostate cancer is the most common malignant solid tumour in men aged >70 years and is the second most common cause of death from oncological circumstances. AIM: To evaluate the effect of different short-term prophylactic antibiotic regimens in transrectal prostate biopsy (PB) on the incidence of infectious complications. METHODS: Patients who underwent transrectal ultrasound-guided PB between January 2021 and December 2022 were included in the prospective randomized study. According to the regimen of prophylaxis, patients were randomized into three groups: (1) fosfomycin trometamol 3 g, 3 h before the procedure + ciprofloxacin 500 mg, 2 h before the procedure; (2) fosfomycin trometamol 3 g, 3 h before and 24 h after the procedure; (3) ciprofloxacin 500 mg 12, 2 h before the procedure, and 12 h after the procedure. A rectal swab was performed 1-2 weeks before PB to evaluate the culture findings. Complications were evaluated during follow-up visits within one month after PB. FINDINGS: In the monitored period, 605 PBs were performed, and 544 patients met the inclusion criteria (184, 161, and 199 in groups 1, 2, and 3). Infectious complications occurred in 10 cases (1.83%), namely 3, 4, and 3 according to patient groups. There was no statistically significant difference between the individual groups. None of the patients required hospitalization and all were free of symptoms of sepsis. CONCLUSION: Short-term antibiotic prophylaxis in PB using fosfomycin trometamol, ciprofloxacin, or their combination appears to be effective. Fosfomycin trometamol is a suitable alternative to fluoroquinolone antibiotics.

• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Antibiotic Prophylaxis methods   MeSH
• Biopsy adverse effects   methods   MeSH
• Ciprofloxacin therapeutic use   MeSH
• Fosfomycin * therapeutic use   MeSH
• Humans MeSH
• Prospective Studies MeSH
• Prostate * diagnostic imaging   pathology   MeSH
• Rectum MeSH
• Tromethamine MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

OBJECTIVE: The purpose of this study was to identify a panel of biomarkers for distinguishing early stage sepsis patients from non-infected trauma patients. BACKGROUND: Accurate differentiation between trauma-induced sterile inflammation and real infective sepsis poses a complex life-threatening medical challenge because of their common symptoms albeit diverging clinical implications, namely different therapies. The timely and accurate identification of sepsis in trauma patients is therefore vital to ensure prompt and tailored medical interventions (provision of adequate antimicrobial agents and if possible eradication of infective foci) that can ultimately lead to improved therapeutic management and patient outcome. The adequate withholding of antimicrobials in trauma patients without sepsis is also important in aspects of both patient and environmental perspective. METHODS: In this proof-of-concept study, we employed advanced technologies, including Matrix-Assisted Laser Desorption/Ionization (MALDI) and multiplex antibody arrays (MAA) to identify a panel of biomarkers distinguishing actual sepsis from trauma-induced sterile inflammation. RESULTS: By comparing patient groups (controls, infected and non-infected trauma and septic shock patients under mechanical ventilation) at different time points, we uncovered distinct protein patterns associated with early trauma-induced sterile inflammation on the one hand and sepsis on the other hand. SYT13 and IL1F10 emerged as potential early sepsis biomarkers, while reduced levels of A2M were indicative of both trauma-induced inflammation and sepsis conditions. Additionally, higher levels of TREM1 were associated at a later stage in trauma patients. Furthermore, enrichment analyses revealed differences in the inflammatory response between trauma-induced inflammation and sepsis, with proteins related to complement and coagulation cascades being elevated whereas proteins relevant to focal adhesion were diminished in sepsis. CONCLUSIONS: Our findings, therefore, suggest that a combination of biomarkers is needed for the development of novel diagnostic approaches deciphering trauma-induced sterile inflammation from actual infective sepsis.

• MeSH
• Anti-Infective Agents * MeSH
• Biomarkers MeSH
• Communicable Diseases * complications   MeSH
• Humans MeSH
• Sepsis * complications   diagnosis   MeSH
• Shock, Septic * complications   MeSH
• Synaptotagmins MeSH
• Inflammation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH