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Search Results (473)

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Case Report
First Case Report of Choledochoenterostomy in a Cat with Biliary Obstruction Due to Cholangiohepatitis and Papillary Stenosis
by Nicole Diana Wolf, Juliette Bénédicte Burg-Personnaz, Jennifer Stéphanie Eiermann and Simona Vincenti
Animals 2025, 15(17), 2634; https://doi.org/10.3390/ani15172634 (registering DOI) - 8 Sep 2025
Abstract
A 2-year-old male neutered domestic shorthair cat was presented with a 12-month history of anorexia, weight loss, vomiting, polyuria, and polydipsia. Physical examination revealed a responsive but debilitated cat with icteric mucous membranes and a low body-condition score. Laboratory tests showed mild macrocytic [...] Read more.
A 2-year-old male neutered domestic shorthair cat was presented with a 12-month history of anorexia, weight loss, vomiting, polyuria, and polydipsia. Physical examination revealed a responsive but debilitated cat with icteric mucous membranes and a low body-condition score. Laboratory tests showed mild macrocytic anemia, elevated liver enzymes, hyperproteinemia with hypoalbuminemia, hyperbilirubinaemia, and a decreased vitamin B12 level. Abdominal ultrasound revealed marked dilation of the common bile duct (CBD) and gallbladder, consistent with suspected extrahepatic biliary tract obstruction, as well as secondary pancreatic and intrahepatic duct distension. Cytological and bacteriological analyses confirmed bacterial cholangiohepatitis due to a mixed infection with Escherichia coli and Peptostreptococcus canis. Despite initial conservative management, the cat’s clinical condition remained unchanged, prompting exploratory laparotomy. Intraoperative findings confirmed the ultrasonographic suspicions and revealed severe pancreatitis. Based these findings, a cholecystectomy, choledochoenterostomy, and placement of a cholecystostomy tube as well as an abdominal drain and jejunal feeding tube were performed. Postoperatively, the cat initially showed improvement but subsequently developed signs of sepsis requiring intensive care. Although temporary stabilization was achieved, the cat died suddenly ten days after surgery due to unknown causes. This case report highlights the diagnostic and therapeutic challenges associated with bacterial cholangiohepatitis secondary to biliary obstruction in cats and documents the first clinical application of choledochoenterostomy—a surgical procedure previously only described hypothetically in this species. Full article
(This article belongs to the Special Issue Advances in Small Animal Gastrointestinal and Hepatic Diseases)
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17 pages, 693 KB  
Review
Hyperferritinemia and Macrophage Activation Syndrome in Septic Shock: Recent Advances with a Pediatric Focus (2020–2025)
by Efrossini Briassouli, Natalia Syrimi and Stavroula Ilia
Children 2025, 12(9), 1193; https://doi.org/10.3390/children12091193 - 8 Sep 2025
Abstract
Macrophage activation syndrome (MAS), a hyperinflammatory condition driven by uncontrolled immune activation, is widely recognized as a critical complication in pediatric septic shock. This syndrome shares pathophysiological features with hemophagocytic lymphohistiocytosis (HLH) and other cytokine storm syndromes, and it contributes to significant morbidity [...] Read more.
Macrophage activation syndrome (MAS), a hyperinflammatory condition driven by uncontrolled immune activation, is widely recognized as a critical complication in pediatric septic shock. This syndrome shares pathophysiological features with hemophagocytic lymphohistiocytosis (HLH) and other cytokine storm syndromes, and it contributes to significant morbidity and mortality in pediatric and adult patients. Hyperferritinemia—a hallmark of MAS—is not only a diagnostic clue but also a prognostic marker for poor outcomes in sepsis. High ferritin levels are strongly suggestive of MAS, yet even moderate elevations in combination with the trend of ferritin levels can be indicative of heightened mortality risk. Distinguishing MAS from severe sepsis or other hyperinflammatory syndromes in children (such as multisystem inflammatory syndrome in children (MIS-C)) can be challenging, as clinical features often overlap. However, early recognition and timely immunomodulatory therapy, particularly corticosteroids and targeted biologic agents, can be life-saving. Recent advances emphasize a syndromic approach to diagnosing MAS within the spectrum of hyperferritinemic sepsis, using scoring tools or MAS-specific criteria adapted to sepsis or MIS-C contexts. Ongoing studies aim to refine biomarker-based stratification and therapeutic algorithms. This review synthesizes current knowledge on MAS as a complication of sepsis, including the diagnostic importance of ferritin levels, differential diagnosis with other cytokine storm syndromes, and the latest therapeutic approaches. It underscores the importance of early suspicion and intervention to reverse immune dysregulation and improve outcomes in critically ill pediatric patients. Full article
(This article belongs to the Special Issue Diagnosis, Treatment and Outcomes of Pediatric Septic Shock)
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12 pages, 1232 KB  
Article
Midkine Deficiency Attenuates Lipopolysaccharide-Induced Pulmonary Inflammation
by Yoshinori Tanino, Xintao Wang, Takefumi Nikaido, Yuki Sato, Ryuichi Togawa, Natsumi Watanabe, Mishie Tanino, Kenji Kadomatsu and Yoko Shibata
Int. J. Mol. Sci. 2025, 26(17), 8519; https://doi.org/10.3390/ijms26178519 - 2 Sep 2025
Viewed by 196
Abstract
Midkine (MDK) is a multifunctional heparin-binding growth factor, and has been shown to regulate cell growth, survival, and migration. It also plays important roles in several inflammatory diseases such as sepsis. However, the role of MDK in the lungs has not yet been [...] Read more.
Midkine (MDK) is a multifunctional heparin-binding growth factor, and has been shown to regulate cell growth, survival, and migration. It also plays important roles in several inflammatory diseases such as sepsis. However, the role of MDK in the lungs has not yet been elucidated. In the present study, we investigated the role of MDK in pulmonary inflammation experiments using a mouse lipopolysaccharide (LPS)-induced pulmonary inflammation model and human bronchial cells. Wild-type and MDK-deficient mice were administered intratracheally with LPS, and several inflammatory parameters were analyzed. In the wild-type mice, MDK mRNA and protein in lung tissues were significantly increased after intratracheal LPS administration. The MDK-deficient mice showed significantly lower counts of total cells and neutrophils, as well as lower concentrations of total protein and neutrophil chemokines, KC and MIP-2 in bronchoalveolar lavage fluid, compared to wild-type mice. Moreover, mRNA expressions of TNF-α, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2 in lung tissues, as well as the histopathological lung inflammation score, were significantly lower in the MDK-deficient mice. Furthermore, in in vitro experiments using bronchial epithelial cells, LPS stimulation increased mRNA expression of MDK, and MDK knockdown by siRNA decreased LPS-induced TNF-α and CXCL8 upregulation. These findings suggest that deficiency of MDK attenuates LPS-induced pulmonary inflammation, at least in part, through inhibiting inflammatory cytokine and chemokine upregulation in the lungs. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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12 pages, 3524 KB  
Article
Is GDF15 a Feasible Biomarker in Sepsis?
by Ertugrul Yigit, Mehmet Akif Simsek, Merve Huner Yigit, Gorkem Akca, Berat Sonmez and Hakki Uzun
Diagnostics 2025, 15(17), 2224; https://doi.org/10.3390/diagnostics15172224 - 2 Sep 2025
Viewed by 270
Abstract
Background/Objectives: Sepsis is a high-mortality syndrome characterized by organ dysfunction resulting from a dysregulated host response to infection. This study aimed to evaluate the potential of growth differentiation factor 15 (GDF15), a stress-inducible cytokine, as a biomarker in patients diagnosed with urosepsis. [...] Read more.
Background/Objectives: Sepsis is a high-mortality syndrome characterized by organ dysfunction resulting from a dysregulated host response to infection. This study aimed to evaluate the potential of growth differentiation factor 15 (GDF15), a stress-inducible cytokine, as a biomarker in patients diagnosed with urosepsis. Methods: A total of 13 patients diagnosed with urosepsis, based on an increase of ≥2 points in the Sequential Organ Failure Assessment (SOFA) score and positive urine culture, were included in the study. Daily blood samples were collected from patients for 10 days, and serum levels of GDF15, procalcitonin (PCT), and presepsin (P-SEP) were measured by ELISA. C-reactive protein (CRP), blood urea nitrogen (BUN), serum creatinine, estimated glomerular filtration rate (eGFR), hemoglobin, and neutrophil, lymphocyte, and platelet counts were determined using autoanalyzers. Temporal changes were analyzed using the Friedman test, and correlations were analyzed using Spearman’s test. Results: GDF15 levels began to decrease from Day 3, with a significant decline observed from Day 7 compared to Day 1 (p < 0.001). Similar decreasing trends were observed in CRP and PCT levels, whereas presepsin levels did not exhibit significant changes. Significant positive correlations were identified between GDF15 and CRP (r = 0.65, p = 0.015), BUN (r = 0.57, p = 0.041), and creatinine (r = 0.62, p = 0.024), and a significant negative correlation was observed with eGFR (r = −0.62, p = 0.024). No significant correlation was found between GDF15 and presepsin (p > 0.05). Conclusions: GDF15 is a biomarker sensitive to the resolution phase of inflammation and organ dysfunction in sepsis, demonstrating significant temporal changes. It holds potential as an indicator for monitoring clinical progression and assessing prognosis. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Sepsis)
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16 pages, 1905 KB  
Article
Microbiological and Clinical Characteristics of Pediatric Sepsis Patients with and without Septic Shock: A Retrospective Study at a Tertiary Pediatric Hospital in China
by Kai-Cheng Peng, Qin-Yuan Li, Lin Chen, Yan Zhao, Hui Liu, Zhen-Xuan Kong and Zheng-Xiu Luo
Children 2025, 12(9), 1146; https://doi.org/10.3390/children12091146 - 28 Aug 2025
Viewed by 285
Abstract
Background: Pediatric sepsis, a life-threatening condition, often progresses to septic shock. However, microbiological and clinical profiles between pediatric sepsis patients with and without septic shock remain underexplored. Methods: This retrospective cohort study included 1200 pediatric sepsis patients (Phoenix Sepsis Score ≥ 2) from [...] Read more.
Background: Pediatric sepsis, a life-threatening condition, often progresses to septic shock. However, microbiological and clinical profiles between pediatric sepsis patients with and without septic shock remain underexplored. Methods: This retrospective cohort study included 1200 pediatric sepsis patients (Phoenix Sepsis Score ≥ 2) from the Children’s Hospital of Chongqing Medical University between June 2018 and June 2023. Pediatric sepsis patients with septic shock were diagnosed based on the Phoenix Cardiovascular Score being ≥1. Clinical data and pathogens were taken from the electronic medical records and analyzed. Univariate and multivariable logistic regressions were conducted to identify the risk factors for septic shock. Results: Septic shock patients had longer hospital stays (14.8 vs. 12.0 days, p = 0.003) and higher mortality (17.4% vs. 4.7%, p < 0.001) when compared to non-septic-shock patients. Among these two groups, the pathogen prevalence revealed that bacterial pathogens dominated (48.9%), followed by viruses (10.3%). Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus remained the predominant pathogens; Pseudomonas aeruginosa and Mycoplasma pneumoniae were also increased. Combination antibiotic therapy was most frequent in patients with viral and fungal sepsis (79% and 86.5%, respectively). Patients with fungal sepsis had significantly longer hospital stays than those with viral sepsis (20.74 vs. 12.97 days, p = 0.017). Multivariable analysis identified that elevated lactate (OR = 1.49, 95% CI = 1.29–1.75) and pulmonary infection (OR = 2.25, 95% CI = 1.35–3.73) were independent risk factors for septic shock. Conclusions: Children with septic shock had higher mortality and prolonged hospitalization, with distinct microbiological profiles when compared with patients in the non-septic-shock group. Elevated lactate and presence of pulmonary infection are independent risk factors for septic shock. Early recognition of high-risk patients and tailored antimicrobial strategies are critical for improving outcomes. Full article
(This article belongs to the Section Pediatric Allergy and Immunology)
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13 pages, 1190 KB  
Article
Influence of Aspirin on Hospital and Clinical Outcomes in Hepatocellular Carcinoma: Insights from National Data
by Manasa Ginjupalli, Praneeth Bandaru, Anuj Raj Sharma, Jayalekshmi Jayakumar, Raissa Nana Sede Mbakop Forlemu, Ali Wakil, Arnold Forlemu and Madhavi Reddy
Gastroenterol. Insights 2025, 16(3), 33; https://doi.org/10.3390/gastroent16030033 - 28 Aug 2025
Viewed by 367
Abstract
Background: Hepatocellular carcinoma (HCC) is a major global health burden and a leading cause of cancer-related deaths. While aspirin has shown potential chemopreventive effects in chronic liver disease, its impact on clinical outcomes among patients hospitalized with HCC remains under-investigated. Methods: Using the [...] Read more.
Background: Hepatocellular carcinoma (HCC) is a major global health burden and a leading cause of cancer-related deaths. While aspirin has shown potential chemopreventive effects in chronic liver disease, its impact on clinical outcomes among patients hospitalized with HCC remains under-investigated. Methods: Using the National Inpatient Sample (NIS) from 2016 to 2022, we conducted a retrospective cohort study to evaluate the association between aspirin use and clinical outcomes in adult HCC hospitalizations. Patients were stratified based on documented aspirin use, and propensity score matching with inverse probability of treatment weighting (IPTW) was applied to minimize confounding. The primary outcome was in-hospital mortality; secondary outcomes included morbidity-related complications, hospital length of stay, and total charges. Results: Among 337,730 hospitalizations with HCC, 8.37% involved aspirin use. Aspirin users demonstrated significantly lower in-hospital mortality (5.2% vs. 10.09%), with an adjusted odds ratio (OR) of 0.58 (95% CI: 0.50–0.68; p < 0.001). Aspirin use was also associated with shorter hospital stays (5.42 vs. 6.39 days), lower total charges ($80,310 vs. $95,098), and reduced incidence of complications, including acute liver failure, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, sepsis, ICU admission, and acute kidney injury. Importantly, no statistically significant increase in gastrointestinal or variceal bleeding was observed among aspirin users. Conclusions: These findings suggest that aspirin use may reduce mortality, morbidity, and healthcare burden in patients hospitalized with HCC. Full article
(This article belongs to the Special Issue Novelties in Diagnostics and Therapeutics in Hepatology: 2nd Edition)
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18 pages, 7454 KB  
Article
Comparison of Open Versus Minimally Invasive Repair of Colovesical Fistula: A Case Report and Propensity-Matched National Database Analysis
by Alexis Volkert, Anmol Nigam, David Stover, Pravin Meshram, Rubeena Naaz, Chidiebere Onongaya, Sean Huu-Tien Nguyen, Jordan Sauve, Wolfgang Gaertner and James V. Harmon Jr.
J. Clin. Med. 2025, 14(17), 6065; https://doi.org/10.3390/jcm14176065 - 27 Aug 2025
Viewed by 442
Abstract
Background: Colovesical fistulas are abnormal communications between the colon and urinary bladder, most commonly caused by diverticular disease. Although colovesical fistulas are rare, they should be suspected in patients presenting with recurrent urinary tract infections, pneumaturia, or fecaluria. We integrated two case reports [...] Read more.
Background: Colovesical fistulas are abnormal communications between the colon and urinary bladder, most commonly caused by diverticular disease. Although colovesical fistulas are rare, they should be suspected in patients presenting with recurrent urinary tract infections, pneumaturia, or fecaluria. We integrated two case reports with a retrospective national cohort analysis to assess the surgical treatment of colovesical fistulas. Methods: We report two cases of colovesical fistulas, both secondary to sigmoid diverticulitis, treated surgically via minimally invasive approaches. A retrospective analysis using the National Inpatient Sample database from 2016 to 2022 was conducted to compare outcomes of open surgery with those of minimally invasive surgery. Propensity score matching and multivariable regression analyses were used to evaluate clinical outcomes. Results: The first patient underwent hand-assisted laparoscopic sigmoidectomy with fistula takedown and has remained asymptomatic at 8 months, while the second patient underwent robotic-assisted sigmoidectomy with staged ileostomy reversal and has remained asymptomatic at 1 month. National data analysis showed no significant difference in mortality (<1% versus <1%, p = 0.931), wound complications (1.4% versus 1.0%; p = 0.554), or postoperative sepsis or shock (7.1% versus 5.6%; p = 0.114) between open and minimally invasive surgical approaches. However, the minimally invasive surgery group had significantly shorter length of stay than the open surgery group (6.9 versus 7.3 days, p < 0.001). Conclusions: Minimally invasive repair of colovesical fistulas was associated with shorter hospital stays than open surgery, with no significant differences in major complications. Early identification and timely surgical management are critical for achieving favorable outcomes. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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11 pages, 1113 KB  
Article
Are Scoring Systems Useful in Predicting Mortality from Upper GI Bleeding in Geriatric Patients?
by Mustafa Zanyar Akkuzu and Berat Ebik
Diagnostics 2025, 15(17), 2173; https://doi.org/10.3390/diagnostics15172173 - 27 Aug 2025
Viewed by 348
Abstract
Background/Objectives: This study aimed to determine the in-hospital mortality rate after upper gastrointestinal (GI) bleeding in geriatric patients with comorbidities. Additionally, it sought to identify effective cut-off values for predicting high-risk patients using AIMS65 and Rockall scores and to assess the impact [...] Read more.
Background/Objectives: This study aimed to determine the in-hospital mortality rate after upper gastrointestinal (GI) bleeding in geriatric patients with comorbidities. Additionally, it sought to identify effective cut-off values for predicting high-risk patients using AIMS65 and Rockall scores and to assess the impact of oral anticoagulant and NSAID use on mortality. Methods: A retrospective cohort study was conducted on 64 patients aged 60 and above with at least one comorbidity who were admitted for upper GI bleeding between January 2023 and June 2024. AIMS65 and Rockall scores were calculated for each patient. The relationship between these scores, medication use, and mortality was analyzed using statistical methods, including ROC analysis and Kaplan–Meier survival curves. Results: The mean age was 77.6 years, and all patients had at least one chronic disease; 57.8% used medications increasing bleeding risk. In-hospital mortality was 18.7%, with no significant association for oral anticoagulants (p = 0.275) or NSAIDs (p = 0.324). Sepsis, heart failure, chronic renal failure, and malignancy were strongly linked to mortality in univariate analysis; multivariate analysis confirmed sepsis and malignancy as independent predictors, with a trend for heart failure. AIMS65 ≥ 2 (sensitivity 90.1%, AUC = 0.920) and Rockall ≥ 6 (sensitivity 91.7%, AUC = 0.822) were both effective in predicting mortality, with risk rising cumulatively with higher scores (p < 0.001). Conclusions: In-hospital mortality after upper GI bleeding is high in elderly patients with multiple comorbidities, mainly from sepsis, malignancy, and heart failure. AIMS65 and Rockall scores effectively predict mortality and may support earlier intervention. The small, high-risk cohort limits generalizability, underscoring the need for multicenter validation. Full article
(This article belongs to the Special Issue New Insights into Gastrointestinal Endoscopy)
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16 pages, 660 KB  
Review
The Potential of Artificial Intelligence in the Diagnosis and Prognosis of Sepsis: A Narrative Review
by George Țocu, Elena Lăcrămioara Lisă, Dana Tutunaru, Raul Mihailov, Cristina Șerban, Valerii Luțenco, Florentin Dimofte, Mădălin Guliciuc, Iulia Chiscop, Bogdan Ioan Ștefănescu, Elena Niculeț, Gabriela Gurău, Sorin Ion Berbece, Oana Mariana Mihailov and Loredana Stavăr Matei
Diagnostics 2025, 15(17), 2169; https://doi.org/10.3390/diagnostics15172169 - 27 Aug 2025
Viewed by 579
Abstract
Background/Objectives: Sepsis is a severe medical condition characterized by a dysregulated host response to infection, with potentially fatal outcomes, requiring early diagnosis and rapid intervention. The limitations of traditional sepsis identification methods, as well as the complexity of clinical data generated in intensive [...] Read more.
Background/Objectives: Sepsis is a severe medical condition characterized by a dysregulated host response to infection, with potentially fatal outcomes, requiring early diagnosis and rapid intervention. The limitations of traditional sepsis identification methods, as well as the complexity of clinical data generated in intensive care, have driven increased interest in applying artificial intelligence in this field. The aim of this narrative review article is to analyze how artificial intelligence is being used in the diagnosis and prognosis of sepsis, to present the most relevant current models and algorithms, and to discuss the challenges and opportunities related to integrating these technologies into clinical practice. Methods: We conducted a structured literature search for this narrative review, covering studies published between 2016 and 2024 in databases such as PubMed/Medline, Scopus, Web of Science, IEEE Xplore, and Google Scholar. The review covered models based on machine learning (ML), deep neural networks (DNNs), Recurrent Neural Networks (RNNs), and clinical alert systems implemented in hospitals. The clinical data sources used, algorithms applied, system architectures, and performance outcomes are presented. Results: Numerous artificial intelligence models demonstrated superior performance compared to conventional clinical scores (qSOFA, SIRS), achieving AUC values above 0.90 in predicting sepsis and mortality. Systems such as Targeted Real-Time Early Warning System (TREWS) and InSight have been clinically validated and have significantly reduced the time to treatment initiation. However, challenges remain, such as a lack of model transparency, algorithmic bias, difficulties integrating into clinical workflows, and the absence of external validation in multicenter settings. Conclusions: Artificial intelligence has the potential to transform sepsis management through early diagnosis, risk stratification, and personalized treatment. A responsible, multidisciplinary approach is necessary, including rigorous clinical validation, enhanced interpretability, and training of healthcare personnel to effectively integrate these technologies into everyday practice. Full article
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13 pages, 441 KB  
Article
Frailty as an Independent Predictor of Mortality in Patients with Sepsis
by Alejandro Interián, Fernando Ramasco, Angels Figuerola and Rosa Méndez
J. Pers. Med. 2025, 15(9), 398; https://doi.org/10.3390/jpm15090398 - 26 Aug 2025
Viewed by 548
Abstract
Objectives: Personalized sepsis care requires understanding how pre-existing health status can influence outcomes. The aim of this study is to evaluate its impact on in-hospital and 12-month mortality in patients with sepsis, taking into account age, comorbidities, the Charlson Comorbidity Index, frailty, [...] Read more.
Objectives: Personalized sepsis care requires understanding how pre-existing health status can influence outcomes. The aim of this study is to evaluate its impact on in-hospital and 12-month mortality in patients with sepsis, taking into account age, comorbidities, the Charlson Comorbidity Index, frailty, anemia, and the Sequential Organ Failure Score Assessment (SOFA) in the first 24 h. Methods: An observational and retrospective study was conducted using data from the Sepsis Code program at the Hospital Universitario de La Princesa. The relationship between risk factors and mortality, as well as Intensive Care Unit (ICU) admission, was analyzed for the period 2016–2018 using bivariate and multivariate logistic regression. Results: A total of 547 patients were included. In the multivariate analysis, the risk factors independently associated with mortality were Rockwood Clinical Frailty Scale ≥ 5 (OR 2.45, p < 0.05); SOFA ≥ 4 (OR 2.13, p < 0.05); age (OR 1.98, p < 0.05); anemia (OR 1.85, p < 0.05); and specific comorbidities such as ischemic heart disease (OR 2.34, p < 0.05), severe liver disease (OR 3.62, p < 0.05), and metastatic cancer (OR 3.14, p < 0.05). Patients who were frail, had dementia, or heart failure were less likely to be admitted to the ICU. Conclusions: Frailty, comorbidities, age, and anemia are associated with outcomes in patients with sepsis and could be incorporated into mortality prediction models to guide tailored treatment strategies. Full article
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19 pages, 6160 KB  
Article
Modeling Sepsis: Establishment and Validation of a 72-Hour Swine Model of Penetrating Abdominal Trauma
by Catharina Gaeth, Travis R. Madaris, Jamila Duarte, Alvaro Rodriguez, Matthew D. Wegner, Amber Powers and Randolph Stone
Medicina 2025, 61(9), 1523; https://doi.org/10.3390/medicina61091523 - 25 Aug 2025
Viewed by 531
Abstract
Background/Objectives: Fecal peritonitis following penetrating abdominal trauma is a serious condition that often results in sepsis and organ failure. The aim of our study was to develop a novel conscious porcine model of sepsis and organ dysfunction caused by multiple penetrating injuries to [...] Read more.
Background/Objectives: Fecal peritonitis following penetrating abdominal trauma is a serious condition that often results in sepsis and organ failure. The aim of our study was to develop a novel conscious porcine model of sepsis and organ dysfunction caused by multiple penetrating injuries to the small and large intestines. Methods: Twelve female Yorkshire pigs (average weight 50.6 ± 6.5 kg) were divided into two groups: Penetrating Abdominal Trauma (PAT) (n = 8) and Control (n = 4). All surgical procedures were performed under anesthesia with adequate analgesia. In the PAT group, the small and large intestines were punctured, and feces mixed with saline were introduced into the abdominal cavity to induce peritonitis. The Control group received sham surgery with only saline solution. The animals were observed in a conscious state over a period of 72 h, vital parameters were recorded, and blood samples were taken regularly. We adapted a pig-specific SOFA score and developed pig-specific SIRS criteria and NEWS2 score to assess organ function. The model was validated by independent investigators. Results: The survival rate in the PAT group was 75%, with an average survival time of 58.5 h, while all animals in the Control group survived to euthanasia. Monitoring showed pathophysiological changes, such as tachycardia, leucopenia, and thrombocytopenia, indicative of sepsis and organ dysfunction. Blinded investigators independently confirmed the model’s validity. Conclusions: A new swine model of penetrating abdominal trauma and sepsis has been successfully developed that demonstrates significant physiological and immunologic changes comparable to human sepsis. This new model provides a realistic platform for future research into sepsis, its diagnostics, and the evaluation of therapeutic strategies. Full article
(This article belongs to the Section Translational Medicine)
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30 pages, 4541 KB  
Article
Role of Endoplasmic Reticulum Stress-Associated Genes in Septic Neonatal Foals
by Dipak Kumar Sahoo, David Wong, Biswaranjan Paital, Rebecca E. Ruby and Ashish Patel
Antioxidants 2025, 14(8), 1024; https://doi.org/10.3390/antiox14081024 - 21 Aug 2025
Viewed by 947
Abstract
The progression of inflammation during sepsis represents a multifaceted biological cascade that requires effective therapeutic interventions to improve survival. In septic neonatal foals, oxidative stress (OS) arises due to a compromised antioxidant defense system. Oxidative stress may disrupt the functionality of redox-sensitive organelles, [...] Read more.
The progression of inflammation during sepsis represents a multifaceted biological cascade that requires effective therapeutic interventions to improve survival. In septic neonatal foals, oxidative stress (OS) arises due to a compromised antioxidant defense system. Oxidative stress may disrupt the functionality of redox-sensitive organelles, such as the endoplasmic reticulum (ER). Endoplasmic reticulum stress disorder affects multiple cellular signaling pathways, including redox balance, inflammation, and apoptosis, and contributes to the pathogenesis of sepsis. The study aimed to elucidate whether OS conditions in sepsis influenced gene expression associated with ER stress. Blood samples were collected from 7 healthy and 21 hospitalized neonatal foals and processed for RNA extraction. RNA sequencing was employed to identify ER stress-responsive genes. Novel findings reported here indicate activation of the ER stress pathway in foals with sepsis. Several genes associated with ER stress, such as clusterin (CLU), BCL2-like 1 (BCL2L1), ubiquitin specific peptidase 14 (USP14), bifunctional apoptosis regulator (BFAR), and optic atrophy 1 (OPA1), were upregulated and positively correlated with sepsis scores and negatively correlated with the combined activities of antioxidant enzymes. In contrast, X-box binding protein 1 (XBP1), homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1), leucine-rich repeat kinase 2 (LRRK2), and selenoprotein S (SELENOS) were negatively correlated with sepsis scores and were downregulated in sepsis and positively correlated with the combined activities of antioxidant enzymes. Furthermore, a positive correlation was observed between cAMP responsive element binding protein 3 like 2 (CREB3L2) and BCL2L1, as well as between the expressions of USP14 and YOD1 deubiquitinase (YOD1) in sepsis. Similarly, the expression levels of XBP1 and Herpud1 demonstrated a positive correlation with each other in sepsis. Additionally, the downregulation of genes with protective function against OS, such as XBP1, HERPUD1, and SELENOS, in septic foals also highlights their significance in mitigating OS in sepsis treatment. The study reported here highlights the potential of ER stress as a promising therapeutic target and prognostic marker in septic foals. Full article
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17 pages, 1446 KB  
Article
Real-World Outcomes and Prognostic Factors of Polymyxin B Hemoperfusion in Severe Sepsis and Septic Shock: A Seven-Year Single-Center Cohort Study from Taiwan
by Wei-Hung Chang, Ting-Yu Hu and Li-Kuo Kuo
Life 2025, 15(8), 1317; https://doi.org/10.3390/life15081317 - 20 Aug 2025
Viewed by 670
Abstract
Background: Severe sepsis and septic shock remain major contributors to ICU mortality. Polymyxin B hemoperfusion (PMX-HP) has been widely adopted as adjunctive therapy in Asian ICUs for endotoxemia, but its real-world effectiveness and prognostic factors remain uncertain, especially in high Gram-negative settings. [...] Read more.
Background: Severe sepsis and septic shock remain major contributors to ICU mortality. Polymyxin B hemoperfusion (PMX-HP) has been widely adopted as adjunctive therapy in Asian ICUs for endotoxemia, but its real-world effectiveness and prognostic factors remain uncertain, especially in high Gram-negative settings. Methods: This retrospective cohort study included 64 adult patients with severe sepsis or septic shock who received at least one session of PMX-HP in a 25-bed tertiary medical ICU in Taiwan between July 2013 and December 2019. Demographic, clinical, microbiological, and treatment data were extracted. The primary outcome was 28-day mortality. Prognostic factors were analyzed using logistic regression. Results: The mean age was 66.1 ± 12.3 years; 67.2% were male. Pneumonia (29.7%) and intra-abdominal infection (18.8%) were the most common sources of sepsis, with E. coli and K. pneumoniae as leading pathogens. Median APACHE II score at ICU admission was 26 (IQR 21–32), and 79.7% received two PMX-HP sessions. The 28-day mortality rate was 46.9%, with ICU and hospital mortality both 53.1%. Non-survivors were older, had higher APACHE II scores, and more frequent use of continuous renal replacement therapy (CRRT). Positive changes in vasoactive-inotropic score (VIS) after PMX-HP were also more common among non-survivors. Multivariate analysis identified advanced age, higher APACHE II score, and CRRT requirement as independent predictors of mortality. Conclusions: In this real-world Asian ICU cohort, PMX-HP was used mainly for severe cases with a high disease burden and Gram-negative predominance. Despite its frequent use, overall mortality remained high. Prognosis was primarily determined by underlying disease severity, organ dysfunction (especially renal failure), and persistent hemodynamic instability. In this high-severity cohort, mortality appeared to be primarily driven by baseline organ dysfunction and persistent hemodynamic instability; PMX-HP session number or sequencing showed no association with survival. Given the absence of a contemporaneous non-PMX-HP control group, mortality observations in this cohort cannot be causally attributed to PMX-HP and should be interpreted with caution as hypothesis-generating rather than definitive evidence of efficacy. Further multicenter studies are needed to clarify the optimal role of PMX-HP in modern sepsis management. Full article
(This article belongs to the Section Medical Research)
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12 pages, 232 KB  
Article
Minimally Invasive Mitral Valve Surgery in Patients Aged ≥75 Years: An Expanding Standard of Care
by Mariafrancesca Fiorentino, Elisa Mikus, Diego Sangiorgi, Simone Calvi, Antonino Costantino, Elena Tenti, Alberto Tripodi and Carlo Savini
J. Clin. Med. 2025, 14(16), 5798; https://doi.org/10.3390/jcm14165798 - 16 Aug 2025
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Abstract
Background: Right anterior mini-thoracotomy has gained increasing popularity as a preferred approach for mitral valve surgery due to its numerous advantages. This study aims to evaluate the safety and efficacy of this technique in elderly patients. Methods: Between January 2010 and November [...] Read more.
Background: Right anterior mini-thoracotomy has gained increasing popularity as a preferred approach for mitral valve surgery due to its numerous advantages. This study aims to evaluate the safety and efficacy of this technique in elderly patients. Methods: Between January 2010 and November 2024, a total of 4092 adult patients underwent mitral valve repair or replacement at our institution. Of these, 1687 patients were treated using a minimally invasive approach. This analysis focuses on elderly patients aged 75 years and older (n = 402), further subdivided into two groups: 75–79 years (n = 253) and 80 years and older (n = 149). Results: The study population comprised 49.8% male patients. A small percentage (1.7%) had a history of endocarditis, and 6.5% had undergone prior cardiac surgery. The median logistic EuroSCORE was 7.68 (IQR 5.83–11.00), and the median EuroSCORE II was 2.75 (1.71, 4.40). Alternative cannulation strategies, guided by AngioCT scans, can expand the applicability of this technique to patients unsuitable for femoral cannulation. Median durations for cardiopulmonary bypass (CPB) and aortic cross-clamping were 99.5 and 80.0 min, respectively. Median ventilation time was 7 h, and the median ICU stay was 2 days. Atrial fibrillation was the most common postoperative complication (20.9%). A significant proportion of patients (47.8%) required blood transfusions, and 3.0% needed re-exploration for bleeding. The in-hospital mortality rate was 3.7%, with 7 (1.7%) patients requiring postoperative dialysis and 5 (1.2%) experiencing sepsis and multiple organ failure. Patients aged 80 years and older exhibited worse renal function and higher EuroSCOREs compared to the younger group (p < 0.001). However, they had shorter CPB (p = 0.004) and cross-clamp times (p = 0.001) and underwent a higher proportion of valve replacements (p = 0.003). Rates of major complications and in-hospital mortality were comparable between the two age groups. Logistic regression analysis identified the logistic EuroSCORE as the only significant preoperative risk factor (p = 0.001). Conclusions: Right anterior minithoracotomy is a safe and reproducible surgical approach, even in elderly patients, promoting faster recovery with a lower risk of complications. Among patients aged >80 years, despite higher comorbidities and elevated EuroSCORE II, in-hospital outcomes are comparable to those aged 75–79 years. Full article
(This article belongs to the Section Cardiovascular Medicine)
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Article
Decoding Sepsis: A 16-Year Retrospective Analysis of Activation Patterns, Mortality Predictors, and Outcomes from a Hospital-Wide Sepsis Protocol
by Marcio Borges-Sa, Andres Giglio, Maria Aranda, Antonia Socias, Alberto del Castillo, Joana Mena, Sara Franco, Maria Ortega, Yasmina Nieto, Victor Estrada, Roberto de la Rica and Son Llatzer’s Multidisciplinary Sepsis Unit
J. Clin. Med. 2025, 14(16), 5759; https://doi.org/10.3390/jcm14165759 - 14 Aug 2025
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Abstract
Background: Sepsis remains a leading cause of mortality in hospitalized patients. We evaluated characteristics and outcomes of patients identified through a comprehensive hospital-wide sepsis protocol over a 16-year period. Methods: This retrospective cohort study analyzed hospital-wide sepsis protocol activations at a tertiary care [...] Read more.
Background: Sepsis remains a leading cause of mortality in hospitalized patients. We evaluated characteristics and outcomes of patients identified through a comprehensive hospital-wide sepsis protocol over a 16-year period. Methods: This retrospective cohort study analyzed hospital-wide sepsis protocol activations at a tertiary care hospital in Spain from 2006 to 2022. The protocol required at least two SIRS criteria plus evidence of organ dysfunction in patients over 14 years old. We analyzed demographics, activation criteria, hospital location, mortality predictors using univariate and multivariate analyses, including propensity score modeling, and resource utilization trends. Results: A total of 10,919 patients with 14,546 protocol activations were identified. The median age was 69 years (IQR: 56–78), with 60.9% male patients. Protocol activations occurred in the emergency department (54%), ICU (34.2%), and inpatient wards (11.8%). The most common SIRS criteria were tachycardia (75.6%), tachypnea (50.4%), and fever (48.5%). Prevalent organ dysfunctions included hypotension (53%), hypoxemia (50.1%), oliguria (28.9%), and altered mental status (22%). Overall in-hospital mortality showed a significant linear downward trend from 26.5% in the first year to 13.6% in later years (p < 0.01). Propensity score analysis confirmed independent mortality predictors included hyperlactatemia (aOR 2.21), altered consciousness (aOR 2.09), hypotension (aOR 1.87), and leukopenia (aOR 1.79). ICU admission rate decreased from 58% to 24% over the study period. Conclusions: This 16-year analysis shows that comprehensive hospital-wide sepsis protocols achieve sustained mortality reduction with improved resource utilization efficiency. These findings support implementing comprehensive sepsis protocols as an effective strategy for improving sepsis outcomes. Full article
(This article belongs to the Special Issue Sepsis: New Insights into Diagnosis and Treatment)
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