Search Results (3,627)

Introduction: Renal malacoplakia is a rare chronic granulomatous disease, often associated with immunosuppression and persistent Gram-negative infections, particularly Escherichia coli. Case Presentation: We present a case involving a 31-year-old woman with hypertension, gestational diabetes, and prior uterine curettage after labor induction for preeclampsia at 23 weeks. She developed urinary sepsis post-procedure. Imaging revealed bilateral nephromegaly, while laboratory tests showed acute kidney injury (KDIGO stage III), anemia, and thrombocytopenia. Blood and urine cultures grew Escherichia coli. Renal biopsy confirmed malacoplakia, demonstrating PAS-positive Michaelis–Gutmann bodies and Von Hansemann cells. The patient responded to prolonged antibiotic therapy and supportive care. Discussion and Conclusion: This case highlights the importance of considering renal malacoplakia in patients with atypical urinary tract infections and nephromegaly, particularly in obstetric settings. Histopathological confirmation is essential, and timely treatment with intracellularly active antibiotics can lead to favorable outcomes. Early diagnosis is critical to prevent irreversible renal damage. 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

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical public health threat due to its rapid nosocomial dissemination, limited therapeutic options, and elevated mortality rates. This study aimed to characterize the epidemiology, carbapenemase profiles, and antimicrobial susceptibility patterns of CRKP isolates, as well as the clinical features and outcomes observed in infected or colonized patients. Materials and Methods: We conducted a retrospective analysis of clinical and microbiological data from patients with CRKP infections or colonization admitted between January 2023 and January 2024. Descriptive statistics were used to assess prevalence, resistance patterns, and patient outcomes. Two binary logistic regression models were applied to identify independent predictors of sepsis and in-hospital mortality. Results: Among 89 CRKP isolates, 45 underwent carbapenemase typing. More than half were metallo-β-lactamase (MBL) producers, with 44.4% co-harbouring NDM and OXA-48-like enzymes. Surgical intervention was associated with a significantly lower risk of sepsis (p < 0.01) and in-hospital mortality (p = 0.045), whereas intensive care unit (ICU) stay was a strong predictor of both outcomes. ICU admission conferred a 10-fold higher risk of sepsis (95%Cl 2.4–41.0) and a 40.8-fold higher risk of in-hospital death (95% Cl 3.5–473.3). Limitations: This single-center retrospective study included a limited number of isolates in certain groups. Additionally, cefiderocol (FDC) susceptibility was assessed by disk diffusion rather than by the broth microdilution method. Conclusions: Our study underscores the increasing prevalence of metallo-beta-lactamase-producing CRKP, particularly strains harbouring dual carbapenemases. Timely recognition of high-risk patients, combined with the implementation of targeted infection control measures and the integration of novel therapeutic options, is crucial to optimize clinical management and reduce mortality associated with CRKP. 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: Right ventricular (RV) dysfunction is associated with poor clinical outcomes in critically ill sepsis patients, but its pathophysiology and predictors are incompletely characterized. We aimed to investigate the predictors of RV dysfunction and its outcomes in sepsis patients admitted to the intensive care unit (ICU). Methods: This is a single-center retrospective cohort study of adult patients admitted to the ICU for sepsis who had echocardiography within 72 h of diagnosis. Patients with acute coronary syndrome, acute decompensated heart failure, or significant valvular dysfunction were excluded. RV dysfunction was defined as the presence of RV dilation, hypokinesis, or both. Demographics and clinical outcomes were obtained from electronic medical records. Results: A total of 361 patients were included in our study—47 with and 314 without RV dysfunction. The mean age of the population was 66.8 years and 54.6% were females. Compared to those without RV dysfunction, patients with RV dysfunction were more likely to require mechanical ventilation (63.8% vs. 43.9%, p = 0.01) and vasopressor support (61.7% vs. 36.6%, p < 0.01). On multivariate logistic regression analysis, increasing age (OR 1.03, 95% C.I. 1.00–1.06), a history of HIV infection (OR 5.88, 95% C.I. 1.57–22.11) and atrial fibrillation (OR 4.34, 95% C.I. 1.83–10.29), and presence of LV systolic dysfunction (OR 14.40, 95% C.I. 5.63–36.84) were independently associated with RV dysfunction. Patients with RV dysfunction had significantly worse 30-day survival (Log-Rank p = 0.023). On multivariate Cox regression analysis, older age (HR 1.02, 95% C.I. 1.00–1.04) and peak lactate (HR 1.16, 95% C.I. 1.11–1.21) were independent predictors of 30-day mortality. Conclusions: Among other findings, our data suggests a possible association between a history of HIV infection and RV dysfunction in critically ill sepsis patients, and this should be investigated further in future studies. Patients with evidence of RV dysfunction had poorer survival in this population; however this was not an independent predictor of mortality in the multivariate analysis. A larger cohort with a longer follow-up period may provide further insights. Full article

The genotoxin colibactin, a complex secondary metabolite, targets eukaryotic cell cycle machinery and contributes to neonatal sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) XM, which produces this genotoxin, is an agent of poultry diseases with zoonotic potential. In this study, we confirmed that clbF was necessary for the APEC XM strain to produce colibactin, but it did not affect the growth, adhesion, or invasion of cells. Deletion of clbF substantially diminished both virulence and systemic dissemination, but it also changed the gene expression of the antiserum survival factor, adherence and invasion, iron acquisition genes, and the secretion system. In conclusion, clbF is necessary for the synthesis of the genotoxin colibactin and affects the development of APEC meningitis in mice. Full article

Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, characterized by an initial hyperinflammatory phase frequently followed by compensatory immunosuppression (CARS). Regulatory T cells (Tregs) play a critical, biphasic role: inadequate suppression during early hyperinflammation fails to control cytokine storms, while excessive/persistent activity in late-phase immunosuppression drives immune paralysis and secondary infection susceptibility. This review explores advances in targeting Treg immunoregulation across bacterial, viral, and fungal sepsis, where pathogenic type critically influenced the types of immunoresponses, shaping Treg heterogeneity in terms of phenotype, survival, and function. Understanding this multifaceted Treg biology offers novel therapeutic avenues, highlighting the need to decipher functional heterogeneity and develop precisely timed, pathogen-tailored immunomodulation to safely harness beneficial Treg roles while mitigating detrimental immunosuppression. Full article

Background/Objectives: Antibiotic use is common among hospitalized pediatric patients. However, inappropriate use, including excessive use of Watch antibiotics, can contribute to antimicrobial resistance, adverse events, and increased healthcare costs. Consequently, there is a need to continually assess their usage among this vulnerable population. This was the objective behind this study. Methods: The medical records of all pediatric patients (under 12 years) admitted and treated with antibiotics at a Ghanaian Teaching Hospital between January 2022 and March 2022 were extracted from the hospital’s electronic database. The prevalence and appropriateness of antibiotic use were based on antibiotic choices compared with current guidelines. Influencing factors were also assessed. Results: Of the 410 admitted patients, 319 (77.80%) received at least one antibiotic. The majority (68.65%; n = 219/319) were between 0 and 2 years, and males (54.55%; n = 174/319). Ceftriaxone was the most commonly prescribed antibiotic (20.69%; n = 66/319), and most of the systemic antibiotics used belonged to the WHO Access and Watch groups, including a combination of Access and Watch groups (42.90%; n = 136/319). Neonatal sepsis (24.14%; n = 77/319) and pneumonia (14.42%; n = 46/319) were the most common diagnoses treated with antibiotics. Antibiotic appropriateness was 42.32% (n = 135/319). Multivariate analysis revealed ceftriaxone prescriptions (aOR = 0.12; CI = 0.02–0.95; p-value = 0.044) and surgical prophylaxis (aOR = 0.07; CI = 0.01–0.42; p-value = 0.004) were associated with reduced antibiotic appropriateness, while a pneumonia diagnosis appreciably increased this (aOR = 15.38; CI = 3.30–71.62; p-value < 0.001). Conclusions: There was high and suboptimal usage of antibiotics among hospitalized pediatric patients in this leading hospital. Antibiotic appropriateness was influenced by antibiotic type, diagnosis, and surgical prophylaxis. Targeted interventions, including education, are needed to improve antibiotic utilization in this setting in Ghana and, subsequently, in ambulatory care. Full article

Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping review of reviews of AI/ML applications spanning reproductive, prenatal, postpartum, neonatal, and early child-development care. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus through April 2025. Two reviewers independently screened records, extracted data, and assessed methodological quality using AMSTAR 2 for systematic reviews, ROBIS for bias assessment, SANRA for narrative reviews, and JBI guidance for scoping reviews. Results: Thirty-nine reviews met our inclusion criteria. In preconception and fertility treatment, convolutional neural network-based platforms can identify viable embryos and key sperm parameters with over 90 percent accuracy, and machine-learning models can personalize follicle-stimulating hormone regimens to boost mature oocyte yield while reducing overall medication use. Digital sexual-health chatbots have enhanced patient education, pre-exposure prophylaxis adherence, and safer sexual behaviors, although data-privacy safeguards and bias mitigation remain priorities. During pregnancy, advanced deep-learning models can segment fetal anatomy on ultrasound images with more than 90 percent overlap compared to expert annotations and can detect anomalies with sensitivity exceeding 93 percent. Predictive biometric tools can estimate gestational age within one week with accuracy and fetal weight within approximately 190 g. In the postpartum period, AI-driven decision-support systems and conversational agents can facilitate early screening for depression and can guide follow-up care. Wearable sensors enable remote monitoring of maternal blood pressure and heart rate to support timely clinical intervention. Within neonatal care, the Heart Rate Observation (HeRO) system has reduced mortality among very low-birth-weight infants by roughly 20 percent, and additional AI models can predict neonatal sepsis, retinopathy of prematurity, and necrotizing enterocolitis with area-under-the-curve values above 0.80. From an operational standpoint, automated ultrasound workflows deliver biometric measurements at about 14 milliseconds per frame, and dynamic scheduling in IVF laboratories lowers staff workload and per-cycle costs. Home-monitoring platforms for pregnant women are associated with 7–11 percent reductions in maternal mortality and preeclampsia incidence. Despite these advances, most evidence derives from retrospective, single-center studies with limited external validation. Low-resource settings, especially in Sub-Saharan Africa, remain under-represented, and few AI solutions are fully embedded in electronic health records. Conclusions: AI holds transformative promise for perinatal care but will require prospective multicenter validation, equity-centered design, robust governance, transparent fairness audits, and seamless electronic health record integration to translate these innovations into routine practice and improve maternal and neonatal outcomes. Full article

Background: The identification and clinical implementation of robust biomarkers are essential for improving diagnosis, prognosis, and treatment across a wide range of diseases. Pancreatic stone protein (PSP) has recently emerged as a promising candidate biomarker. Objective: This narrative review aims to provide an updated and comprehensive overview of the clinical applications of PSP in infectious, oncological, metabolic, and surgical contexts. Methods: We conducted a structured literature search using PubMed^®, applying the SANRA framework for narrative reviews. Boolean operators were used to retrieve relevant studies on PSP in a wide range of clinical conditions, including sepsis, gastrointestinal cancers, diabetes, and ventilator-associated pneumonia. Results: PSP has shown strong diagnostic and prognostic potential in sepsis, where it may outperform traditional markers such as CRP and PCT. It has also demonstrated relevance in gastrointestinal cancers, type 1 and type 2 diabetes, and perioperative infections. PSP levels appear to rise earlier than other inflammatory markers and may be less affected by sterile inflammation. Conclusion: PSP represents a versatile and clinically valuable biomarker. Its integration into diagnostic protocols could enhance early detection and risk stratification in critical care and oncology settings. However, widespread adoption is currently limited by the availability of point-of-care assay platforms. Full article

Background: COVID-19-associated coagulopathy (CAC) is a complex condition, with high rates of thrombosis, high levels of inflammation markers and hypercoagulation (increased levels of fibrinogen and D-Dimer), as well as extensive microthrombosis in the lungs and other organs of the deceased. It resembles, without being identical, other coagulation disorders such as sepsis-DIC (SIC/DIC), hemophagocyte syndrome (HPS) and thrombotic microangiopathy (TMA). Platelets (PLTs), key regulators of thrombosis, inflammation and immunity, are considered an important risk mediator in COVID-19 pathogenesis. Platelet index MPV/PLT ratio is reported in the literature as more specific in the prognosis of platelet-related systemic thrombogenicity. Studies of MPV/PLT ratio with regards to the severity of COVID-19 disease are limited, and there are no references regarding this ratio to the outcome of COVID-19 disease at specific time points of hospitalization. The aim of this study is to evaluate the relationship of COVID-19 mortality with the red cell distribution width–coefficient of variation (RDW-CV), platelets and MPV/PLT ratio parameters. Methods: Values of these parameters in 511 COVID-19 hospitalized patients were recorded (a) on admission, (b) as mean values of the 1st and 2nd week of hospitalization, (c) over the total duration of hospitalization, (d) as nadir and zenith values, and (e) at discharge. Results: As for mortality (survivors vs. deceased), statistical analysis with ROC curves showed that regarding the values of the parameters on admission, only the RDW-CV baseline was of prognostic value. Platelet parameters, absolute number and MPV/PLT ratio had predictive potential for the disease outcome only as 2nd week values. On the contrary, with regards to disease severity (mild/moderate versus severe/critical), only the MPV/PLT ratio on admission can be used for prognosis, and to a moderate degree. On multivariable logistic regression analysis, only the RDW-CV mean hospitalization value (RDW-CV mean) was an independent and prognostic variable for mortality. Regarding disease severity, the MPV/PLT ratio on admission and RDW-CV mean were independent and prognostic variables. Conclusions: RDW-CV, platelets and MPV/PLT ratio hematological parameters could be of predictive value for mortality and severity in COVID-19 disease, depending on the hospitalization timeline. Full article

Sepsis is a serious public health problem. sTREM-1 is a marker of inflammatory and infectious processes that has the potential to become a useful tool for predicting the evolution of sepsis. A prediction model for sepsis was constructed by combining sTREM-1, CRP, and a leukogram via a Bayesian network. A translational study carried out with 32 children with congenital heart disease who had undergone surgical correction at a public referral hospital in Northeast Brazil. In the postoperative period, the mean value of sTREM-1 was greater among patients diagnosed with sepsis than among those not diagnosed with sepsis (394.58 pg/mL versus 239.93 pg/mL, p < 0.001). Analysis of the ROC curve for sTREM-1 and sepsis revealed that the area under the curve was 0.761, with a 95% CI (0.587–0.935) and p = 0.013. With the Bayesian model, we found that a 100% probability of sepsis was related to postoperative blood concentrations of CRP above 71 mg/dL, a leukogram above 14,000 cells/μL, and sTREM-1 concentrations above the cutoff point (283.53 pg/mL). The proposed model using the Bayesian network approach with the combination of CRP, leukocyte count, and postoperative sTREM-1 showed promise for the diagnosis of sepsis. 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/Objectives: Infants with high-output enterostomies often require prolonged parenteral nutrition (PN), increasing risks of infections, liver dysfunction, and impaired growth. Mucous fistula refeeding (MFR) is proposed to enhance intestinal adaptation, weight gain, and distal bowel maturation. This systematic review and meta-analysis assessed its effectiveness, safety, and technical aspects. Methods: Following PRISMA guidelines, studies reporting MFR-related outcomes were included without data or language restrictions. Data sources included PubMed, EMBASE, CINAHL, Scopus, Web of Science, Cochrane Library, and UpToDate. Bias risk was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Meta-analysis employed random- and fixed-effects models, with outcomes reported as odds ratios (ORs) and 95% confidence interval (CI). Primary outcomes assessed were weight gain, PN duration, and complications and statistical comparisons were made between MFR and non-MFR groups. Results: Seventeen studies involving 631 infants were included; 482 received MFR and 149 did not. MFR started at 31 postoperative days and lasted for 50 days on average, using varied reinfusion methods, catheter types, and fixation strategies. MFR significantly improved weight gain (4.7 vs. 24.2 g/day, p < 0.05) and reduced PN duration (60.3 vs. 95 days, p < 0.05). Hospital and NICU stays were also shorter (160 vs. 263 days, p < 0.05; 122 vs. 200 days, p < 0.05). Cholestasis risk was lower (OR 0.151, 95% CI 0.071–0.319, p < 0.0001), while effects on bilirubin levels were inconsistent. Complications included sepsis (3.5%), intestinal perforation (0.83%), hemorrhage (0.62%), with one MFR-related death (0.22%). Conclusions: Despite MFR benefits neonatal care, its practices remain heterogeneous. Standardized protocols are required to ensure MFR safety and efficacy. Full article

Sepsis is a fetal disease that requires a clear diagnostic biomarker for timely antibiotic treatment. Recent research has identified a pyroptosis-inducing epitope known as P5-5 in tetranectin (TN), a plasma protein produced by monocytes. Previously, we produced a 12F1 monoclonal antibody against the P5-5 and discovered that it could not only diagnose the presence but also monitor the progress of sepsis in the clinic. In the current study, we further investigated the structure site of the P5-5 and the recognition mechanism between the 12F1 mAb and the P5-5 epitope. To this end, 10 amino acids (NDALYEYLRQ) in the P5-5 were individually mutated to alanine, and their binding to the mAb was tested to confirm the most significant antigenic recognition sites. In the meanwhile, the spatial conformation of 12F1 mAb variable regions was modeled, and the molecular recognition mechanisms in detail of the mAb to the P5-5 epitope were further studied by molecular docking. Following epitope prediction and experimental verification, we demonstrated that the motif “DALYEYL” in the epitope sequence position 2−8 of TN-P5-5 is the major binding region for mAb recognition, in which two residues (4L and 8L) were essential for the interaction between the P5-5 epitope and the 12F1 mAb. Therefore, our study greatly narrowed down the previously reported motif from ten to seven amino acids and identified two Leu as critical contact residues. Finally, a single-chain variable fragment (scFv) from the 12F1 hybridoma was constructed, and it was confirmed that the identified motif and residues are prerequisites for the strong binding between P5-5 and 12F1. Altogether, the data of the present work could serve as a theoretic guide for the clinical design of biosynthetic drugs by artificial intelligence to treat sepsis. Full article