Search Results (1,794)

Introduction: Septic-induced cardiomyopathy (SICM) is a life-threatening condition in patients with septic shock. Persistent hypoperfusion despite adequate volume status and vasopressor use is associated with poor outcomes and is currently managed with inotropes. However, the superiority of available inotropic agents remains unclear. This meta-analysis aims to determine which inotropic agent may be more effective in this clinical scenario. Methods: A systematic review and meta-analysis were conducted, including data from randomized clinical trials (RCTs) comparing levosimendan and dobutamine in patients with septic shock and persistent hypoperfusion. Summary effect estimates, including odds ratios (ORs), standardized mean differences (SMDs), and 95% confidence intervals (CIs), were calculated using a random-effects model. Trial sequential analysis (TSA) was also performed. Results: Of 244 studies screened, 11 RCTs were included. Levosimendan was associated with a reduction in in-hospital mortality (OR 0.64; 95% CI: 0.47; 0.88) and ICU length of stay (SMD 5.87; 95% CI: –8.37; 20.11) compared with dobutamine. Treatment with levosimendan also resulted in significant reductions in BNP (SMD –1.87; 95% CI: –2.45; −1.2) and serum lactate levels (SMD –1.63; 95% CI: –3.13; −0.12). However, TSA indicated that the current evidence is insufficient to definitively confirm or exclude effects on in-hospital and 28-day mortality. Conclusions: Levosimendan may improve hemodynamics, tissue perfusion, and biomarkers, and may reduce in-hospital mortality and ICU length of stay in patients with SICM compared with dobutamine. However, TSA highlights the need for further studies to inform clinical practice and optimize inotrope selection. Full article

Endotoxemia is commonly observed in donkeys, secondary to colic, pleuropneumonia, or diarrhea among other disorders. Hematologic ratios are new biomarkers widely used in the diagnosis and prognosis of multiple conditions in human medicine, including sepsis. While the utility of these ratios has been proved in septic foals, no data are available on donkeys. Moreover, reference intervals (RIs) have not been studied in this species. In this study, RIs of the most commonly reported hematologic ratios were determined in 73 healthy adult donkeys. In addition, variations in these ratios in response to LPS infusion were also evaluated in six healthy adult donkeys. Most of the ratios evaluated showed significant variations after induced endotoxemia, with most of them showing values outside of the established RIs. Similarly to septic foals, the neutrophil to lymphocyte ratio was significantly reduced after LPS infusion. No significant changes were observed in the red cell distribution width to platelet ratio, contrary to reports on septic foals. Previously reported cut-off values for both of these ratios should not be extrapolated to donkeys. Future studies evaluating these ratios in natural endotoxemia or other diseases in donkeys, as well as establishing species-specific cut-off values, are necessary. Full article

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of chromatin DNA, histones, and granular proteins released by neutrophils through a specialized form of cell death known as NETosis. While NETs contribute to the containment of pathogens, their excessive or dysregulated production in sepsis is associated with endothelial damage, immunothrombosis, and organ dysfunction. Several NET-associated biomarkers have been identified, including circulating cell-free DNA (cfDNA), histones, MPO-DNA complexes, and neutrophil elastase–DNA complexes, which correlate with the disease severity and prognosis. Therapeutic strategies targeting NETs are currently under investigation. Inhibition of NET formation using PAD4 inhibitors or ROS scavengers has shown protective effects in preclinical models. Conversely, DNase I therapy facilitates the degradation of extracellular DNA, reducing the NET-related cytotoxicity and thrombotic potential. Additionally, heparin and its derivatives have demonstrated the ability to neutralize NET-associated histones and mitigate coagulopathy. Novel approaches include targeting upstream signaling pathways, such as TLR9 and IL-8/CXCR2, offering further therapeutic promise. Full article

We planned a systemic review and meta-analysis to evaluate the diagnostic accuracy of Monocyte Distribution Width (MDW) in aiding the diagnosis of sepsis in the Emergency Department (ED) and Intensive Care Unit (ICU). A systematic literature search was performed in PubMed, Scopus, and OVID to retrieve studies published up to 29 January 2024. We examined results using mean difference and conducted a diagnostic test accuracy (DTA) meta-analysis using a bivariate random effects model. Pooled results showed that MDW was significantly higher in sepsis patients admitted to the ED (MD = 5.59, 95%CI: 4.14–7.05) or to the ICU (MD = 8.30, 95%CI: 2.98–13.62). Nine studies conducted in the ED were included in the DTA review. The overall sensitivity was 0.80 (95%CI: 0.75–0.85), the specificity was 0.76 (95%CI: 0.66–0.83), and the false-positive rate (FPR) was 0.24 (95%CI: 0.17–0.34). Three studies were conducted in the ICU, but only two were included in the DTA meta-analysis. Of the 662 patients admitted to the ICU, 175 developed sepsis, showing higher MDW values than non-septic patients. However, significant heterogeneity was noted among the studies. MDW is a helpful biomarker for sepsis in adult patients admitted to the ED and ICU. In the ED, MDW could aid clinicians in ruling out sepsis. Full article

Background: Septic arthritis is an orthopedic emergency. However, optimal biomarkers and diagnostic criteria remain unclear. The study aimed to evaluate the diagnostic performance of routinely used and novel biomarkers, including serum C-reactive protein (CRP), synovial white blood cells (WBC), pentraxin-3 (PTX3), interleukin-6 (IL-6), and presepsin, in distinguishing septic from non-septic arthritis. Methods: Thirty-one patients undergoing arthrocentesis were included. Patients were categorized into septic and non-septic arthritis groups. Synovial fluid and serum samples were analyzed for five biomarkers. Diagnostic performance was assessed by calculating the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Synovial WBC demonstrated the highest diagnostic performance among single biomarkers (AUC = 0.837, p = 0.012). Among novel biomarkers, PTX3 showed the highest accuracy and sensitivity. The serum CRP and synovial WBC combination yielded an AUC of 0.853, with 100% sensitivity, 68.0% specificity, 42.9% PPV, and 100% NPV. Adding all three novel biomarkers to this combination increased the AUC to 0.887 (p = 0.004), maintaining 100% sensitivity and NPV. When individually added, PTX3 achieved 100% sensitivity and NPV, while presepsin showed the highest specificity (96.0%), PPV (75.0%), and accuracy (87.1%). Conclusions: Serum CRP and synovial WBC remain essential biomarkers for diagnosing septic arthritis; however, combining them with PTX3, IL-6, and presepsin improved diagnostic accuracy. PTX3 is best suited for ruling out septic arthritis due to its high sensitivity and NPV, whereas presepsin is more useful for confirmation, given its specificity and PPV. These results support a tailored biomarker approach aligned with diagnostic intent. Full article

In Gram-negative bacteria, lipopolysaccharides (LPSs, also known as endotoxin) can induce extensive immune responses that will enable victims to produce severe septic shock syndrome. Because of the high mortality of sepsis in the face of standard treatment, advance detoxification schemes are urgently needed in clinics. Herein, we described a supramolecular detoxification approach via direct host–guest complexation by a giant macrocycle. Cationic pentaphen[3]arene (CPP3) bearing multiple quaternary ammonium groups was screened as a candidate antidote. CPP3 exhibited robust binding affinity toward LPS with an association constant of (4.79 ± 0.29) × 10⁸ M⁻¹. Co-dosing with an equivalent amount of CPP3 has been demonstrated to decrease LPS-induced cytotoxicity on a cellular level through inhibiting ROS generation and proinflammatory cytokine expression. In vivo experiments have further proved that post-treatment by CPP3 could significantly improve the survival rate of LPS-poisoned mice from 0 to 100% over a period of 3 days, and inflammatory abnormalities and tissue damage were also alleviated. Full article

Background and Aims: Sepsis-associated acute kidney injury (S-AKI) is common and is associated with poor outcomes. This prospective observational study aimed to assess the predictive value of four novel biomarkers—syndecan-1 (SDC1), neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin (PENK), and presepsin (PSPN)—for renal outcomes and mortality in septic ICU patients. Methods: Serum biomarker levels were measured in serum samples collected at the time of sepsis diagnosis on the basis of the Sepsis-3 criteria. Acute kidney injury (AKI) was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, and patients were grouped by the presence of AKI, renal replacement therapy requirement (RRT), and intensive care unit (ICU) survival. Demographic, clinical, laboratory, and severity score data were compared between groups to evaluate the predictive performance of biomarkers and clinical parameters. Results: Of the 140 septic patients included, 55.0% developed AKI, 17.2% required RRT, and the ICU mortality rate was 50.0%. SDC1 was independently associated with both AKI (OR: 1.201; p = 0.024) and RRT initiation (OR: 1.260; p = 0.004). It also demonstrated the highest predictive performance for RRT (AUC: 0.715; p = 0.001) and a significant AUC for AKI evaluation (AUC: 0.659; p = 0.002). NGAL levels were significantly elevated in patients with AKI and higher SOFA scores but were not independently predictive. PENK and PSPN were not significantly associated with any renal outcome or mortality. The combined SOFA–SDC1 model improved discrimination for both AKI (AUC: 0.770) and RRT (AUC: 0.737), surpassing individual predictors. Conclusions: SDC1 emerged as the most reliable biomarker for assessing AKI and predicting the need for RRT, highlighting its potential role in early renal risk stratification among critically ill patients. Full article

Background/Objective: Sepsis is a leading cause of death in noncoronary intensive care units (ICUs). Fluids for intravascular resuscitation include crystalloids and colloids. There is extensive clinical evidence on colloid use, but large trials comparing gelatine with crystalloid regimens in ICU and septic patients are lacking. This study aimed to determine whether early, protocol-driven volume resuscitation using a gelatine-based regimen achieves hemodynamic stability (HDS) more rapidly than a crystalloid-based regimen in septic patients. Methods: This prospective, controlled, randomised, double-blind, multinational phase IV study compared two parallel groups of septic patients receiving a gelatine-based regimen (Gelaspan^® 4% and Sterofundin^® ISO, B. Braun Melsungen AG each, at a 1:1 ratio) or a crystalloid regimen (Sterofundin^® ISO). Primary endpoint was time to first HDS within 48 h after randomisation. Secondary endpoints included fluid overload, fluid balance, and patient outcomes. Results: 167 patients were randomised. HDS was achieved after 4.7 h in the gelatine group and after 5.8 h in the crystalloid group (p = 0.3716). The gelatine group had a more favourable fluid balance at 24 h (medians: 3463.00 mL vs. 4164.00 mL; p = 0.0395) and less fluid overload (medians: 4296.05 vs. 5218.75%; p = 0.0217). No differences were observed in serious adverse events or mortality. Conclusions: The study provided clinical evidence of balanced gelatine solution for volume resuscitation in septic patients, although it was terminated prematurely. The early and protocol-based administration of gelatine was safe and effective in the enrolled patient population. Time to HDS was not different between groups but the gelatine-based regimen led to better fluid balance and less fluid overload. Full article

Background and Objectives: Severe sepsis complicated by refractory shock is associated with high mortality. Adding continuous hemofiltration to venovenous extracorporeal membrane oxygenation (ECMO) may accelerate clearance of inflammatory mediators and improve haemodynamic stability, but evidence remains limited. We analysed 44 consecutive septic-shock patients treated with combined ECMO-hemofiltration (ECMO group) and compared them with 92 septic-shock patients managed without ECMO or renal replacement therapy (non-ECMO group). Methods: This retrospective single-centre study reviewed adults admitted between January 2018 and March 2025. Demographic, haemodynamic, laboratory and outcome data were extracted from electronic records. Primary outcome was 28-day mortality; secondary outcomes included intensive-care-unit (ICU) length-of-stay, vasopressor-free days, and change in Sequential Organ Failure Assessment (SOFA) score at 72 h. Results: Baseline age (49.2 ± 15.3 vs. 52.6 ± 16.1 years; p = 0.28) and APACHE II (27.8 ± 5.7 vs. 26.9 ± 6.0; p = 0.41) were comparable. At 24 h, mean arterial pressure rose from 52.3 ± 7.4 mmHg to 67.8 ± 9.1 mmHg in the ECMO group (mean change [∆] + 15.5 mmHg, p < 0.001). Controls exhibited a modest 4.9 mmHg rise that did not reach statistical significance (p = 0.07). Inflammatory markers decreased more sharply with ECMO (IL-6 ∆ −778 pg mL⁻¹ vs. −248 pg mL⁻¹, p < 0.001). SOFA fell by 3.6 ± 2.2 points with ECMO versus 1.6 ± 2.4 in controls (p = 0.01). Twenty-eight-day mortality did not differ (40.9% vs. 48.9%, p = 0.43), but ICU stay was longer with ECMO (median 12.5 vs. 9.3 days, p = 0.002). ΔIL-6 correlated with ΔSOFA (ρ = 0.46, p = 0.004). Conclusions: ECMO-assisted hemofiltration improved early haemodynamics and organ-failure scores and accelerated cytokine clearance, although crude mortality remained unchanged. Larger prospective trials are warranted to clarify survival benefit and optimal patient selection. Full article

Infections with multidrug-resistant (MDR) organisms remain a significant cause of morbidity and mortality among liver transplant recipients, despite advances in surgical techniques and immunosuppressive therapy. This prospective observational study aimed to evaluate the impact of targeted perioperative antibiotic prophylaxis against MDR Gram-negative bacteria on postoperative infections and mortality in liver transplant recipients. Seventy-nine adult patients who underwent liver transplantation and were admitted to the ICU for more than 24 h postoperatively were included. Demographics, disease severity scores, comorbidities, and lengths of ICU and hospital stay were recorded. Colonization with carbapenem-resistant Gram-negative bacteria was assessed via preoperative and postoperative cultures from the blood, urine, rectum, and tracheal secretions. Patients were divided into two groups: those with MDR colonization or infection who received targeted prophylaxis and controls who received standard prophylaxis. Infectious complications (30.4%) occurred significantly less frequently than non-infectious ones (62.0%, p = 0.005). The most common infections were bacteremia (22.7%), pneumonia (17.7%), and surgical site infections (2.5%), with most events occurring within 15 days post-transplant. MDR pathogens isolated included Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Although overall complication and mortality rates at 30 days and 3 months did not differ significantly between groups, the targeted prophylaxis group had fewer infectious complications (22.8% vs. 68.5%, p = 0.008), particularly bacteremia (p = 0.007). Infection-related mortality was also significantly reduced in this group (p = 0.039). These findings suggest that identification of MDR colonization and administration of targeted perioperative antibiotics may reduce septic complications in liver transplant patients. Further prospective studies are warranted to confirm benefits on outcomes and resource utilization. Full article

Cat bites frequently lead to polymicrobial infections due to deep puncture wounds that inoculate oral flora into poorly oxygenated tissues. While Pasteurella multocida is the most commonly implicated organism, environmental and atypical pathogens may also play a role, yet often go unrecognized. This article reports a rare case of polymicrobial septic arthritis caused by a domestic cat bite in an immunocompetent adult, with isolation of Rahnella aquatilis, a freshwater-associated Enterobacterales species not previously reported in this context. A 33-year-old immunocompetent male presented with acute hand swelling, pain, and functional impairment within 24 h of the bite. Emergency surgery revealed purulent tenosynovitis and arthritis. Intraoperative cultures identified R. aquatilis, P. multocida, and Pantoea agglomerans. Identification was performed using MALDI-TOF MS. The R. aquatilis isolate was susceptible to beta-lactams (excluding ampicillin), quinolones, and co-trimoxazole. The patient received amoxicillin–clavulanic acid and fully recovered within two weeks. This is the first reported case of joint infection involving R. aquatilis following a cat bite. It highlights the importance of considering environmental Enterobacterales in animal bite wounds, and the utility of advanced microbiological tools for detecting uncommon pathogens. Broader awareness may improve diagnosis and guide targeted therapy in polymicrobial infections. Full article

(1) Background: Murine typhus, caused by Rickettsia typhi, is a neglected rickettsial disease and an underdiagnosed cause of acute febrile illness (AFI), particularly in endemic regions such as Indonesia. (2) Case description: We report a case series of four patients presenting with AFI of less than seven days in duration. Three patients were admitted with moderate disease, while one presented with septic shock with the macrophage activation-like syndrome (MALS) phenotype. Common clinical features included myalgia and headache; additional symptoms included cough, sore throat, and abdominal pain. Laboratory findings revealed bicytopenia, elevated transaminases, and raised inflammatory and bacterial infection markers. Common tropical infections—dengue, typhoid fever, and leptospirosis—and other potential sources of infection were excluded early during hospitalization. Diagnosis was confirmed by nucleic acid amplification testing (NAAT), which detected R. typhi in all patients. Doxycycline was initiated following confirmation, leading to defervescence within 36–48 h. (3) Conclusions: Murine typhus remains an underrecognized cause of febrile illness in Indonesia. In the near future, the inclusion of rickettsial testing in the diagnostic protocol of AFI will be crucial, as it enables timely administration of effective, low-cost treatment. Full article

Introduction: Acute Myeloid Leukemia (AML) is a hematologic malignancy characterized by the clonal expansion of myeloid progenitors. While it primarily affects the bone marrow, extramedullary relapse occurs in 3–5% of cases, and it is linked to poor prognosis. Central nervous system (CNS) involvement presents diagnostic challenges due to nonspecific symptoms. CNS manifestations include leptomeningeal dissemination, nerve infiltration, parenchymal lesions, and myeloid sarcoma, occurring at any disease stage and frequently asymptomatic. Methods: A 62-year-old man with a recent history of AML in remission presented with diplopia and aching paresthesias in the left periorbital region spreading to the left frontal area. The diagnostic workup included neurological and hematological evaluation, lumbar puncture, brain CT, brain magnetic resonance imaging (MRI) with contrast, and dermatological evaluation with skin biopsy due to the appearance of nodular skin lesions on the abdomen and thorax. Results: Neurological evaluation showed hypoesthesia in the left mandibular region, consistent with left trigeminal nerve involvement, extending to the periorbital and frontal areas, and impaired adduction of the left eye with divergent strabismus in the primary position due to left oculomotor nerve palsy. Brain MRI showed an equivocal thickening of the left oculomotor nerve without enhancement. Cerebrospinal fluid (CSF) analysis initially showed elevated protein (47 mg/dL) with negative cytology; a repeat lumbar puncture one week later detected leukemic cells. Skin biopsy revealed cutaneous AML localization. A diagnosis of AML relapse with CNS and cutaneous localization was made. Salvage therapy with FLAG-IDA-VEN (fludarabine, cytarabine, idarubicin, venetoclax) and intrathecal methotrexate, cytarabine, and dexamethasone was started. Subsequent lumbar punctures were negative for leukemic cells. Due to high-risk status and extramedullary disease, the patient underwent allogeneic hematopoietic stem cell transplantation. Post-transplant aplasia was complicated by septic shock; the patient succumbed to an invasive fungal infection. Conclusions: This case illustrates the diagnostic complexity and poor prognosis of extramedullary AML relapse involving the CNS. Early recognition of neurological signs, including cranial nerve dysfunction, is crucial for timely diagnosis and management. Although initial investigations were negative, further analyses—including repeated CSF examinations and skin biopsy—led to the identification of leukemic involvement. Although neuroleukemiosis cannot be confirmed without nerve biopsy, the combination of clinical presentation, neuroimaging, and CSF data strongly supports the diagnosis of extramedullary relapse of AML. Multidisciplinary evaluation remains essential for detecting extramedullary relapse. Despite treatment achieving CSF clearance, the prognosis remains unfavorable, underscoring the need for vigilant clinical suspicion in hematologic patients presenting with neurological symptoms. Full article

There is a present need to develop alternative biotherapeutic drugs to mitigate the exacerbated inflammatory immune responses characteristic of sepsis. The potent endotoxin lipopolysaccharide (LPS), a major component of Gram-negative bacterial outer membrane, activates the immune system via Toll-like receptor 4 (TLR4), triggering macrophages and a persistent cascade of inflammatory mediators. Our previous studies have demonstrated that Fh15, a recombinant member of the Fasciola hepatica fatty acid binding protein family, can significantly increase the survival rate by suppressing many inflammatory mediators induced by LPS in a septic shock mouse model. Although Fh15 has been proposed as a TLR4 antagonist, the specific mechanisms underlying its immunomodulatory effect remained unclear. In the present study, we employed a quantitative proteomics approach using tandem mass tag (TMT) followed by LC-MS/MS analysis to identify and quantify differentially expressed proteins that participate in signaling pathways downstream TLR4 of macrophages, which can be dysregulated by Fh15. Data are available via ProteomeXchange with identifier PXD065520. Based on significant fold change (FC) cut-off of 1.5 and p-value ≤ 0.05 criteria, we focused our attention to 114 proteins that were upregulated by LPS and downregulated by Fh15. From these proteins, TNFα, IL-1α, Lck, NOS2, SOD2 and CD36 were selected for validation by Western blot on murine bone marrow-derived macrophages due to their relevant roles in the NF-κB, iNOS, oxidative stress, and phagosome signaling pathways, which are closely associated with sepsis pathogenesis. These results suggest that Fh15 exerts a broad spectrum of action by simultaneously targeting multiple downstream pathways activated by TLR4, thereby modulating various aspects of the inflammatory responses during sepsis. Full article

Background/Objectives: Platelet transfusions are administered to preterm neonates with thrombocytopenia prophylactically to decrease their bleeding risk. The amplitude difference between the extrinsic rotational thromboelastometry (EXTEM) and the fibrinogen rotational thromboelastometry (FIBTEM) assays is considered an index of platelet contribution to clot strength, guiding transfusion management. The difference in maximum clot elasticity (MCE) (namely the platelet contribution to clot elasticity—MCEplatelet) is considered highly accurate. Limited data exist to specify the contribution of platelets and fibrinogen in clot formation during sepsis in neonates with thrombocytopenia. We investigated the potential of MCFplatelet (platelet contribution to clot firmness) and MCEplatelet in reflecting platelet count and function in septic preterm neonates. We simultaneously assessed the contribution of both platelets and fibrinogen to clot strength during sepsis. Methods: We compared 28 preterm neonates with sepsis born (gestational age 24⁺¹-34⁺³) with 30 healthy counterparts by using rotational thromboelastometry (ROTEM) and platelet flow cytometry. Results: MCEplatelet showed a higher association with platelet count in the sepsis group than MCFplatelet (R² = 47.66% vs. R² = 18.79%). MCEplatelet (AUC = 0.81) had better discrimination capability than MCFplatelet (AUC = 0.78) in platelet count <100 × 10³/L. MCEplatelet was poorly associated with platelet function. The contribution of platelets was significantly lower (MCEplatelet = 84.03 vs. 89.21; p < 0.001) compared with fibrinogen (36.9 vs. 25.92; p < 0.001) in the sepsis group. Conclusions: MCEplatelet has a better predictive value than MCFplatelet. In clinical practice, the elasticity difference between EXTEM and FIBTEM may replace the amplitude difference. The higher contribution of fibrinogen in clot strength during neonatal sepsis results in higher MCF, even in neonates with thrombocytopenia. Full article