OBJECTIVE

This study aimed to identify the different risk factors for developing sepsis in patients undergoing percutaneous nephrolithotomy

METHODS

This is a case-control study of all patients who underwent percutaneous nephrolithotomy in the National Kidney and Transplant Institute from 2017 to 2021. Demographic, stone characteristics, perioperative data and post-operative parameters were recorded. The association of clinical variables and sepsis was determined using logistic regression analysis.

RESULTS

A total of 536 patients who underwent percutaneous nephrolithotomy were included in the study with 58 of them suffering from sepsis with a prevalence rate of 9.9%. The majority [392 (67.82%)] of the patients were 31-59 years old. Majority of patients suffering from sepsis also belonged to the same age group were predominantly male [33 (56.9%)], mostly diabetic [15 (26.32%)] and hypertensive [14 (24.56%)] and underwent previous PCNL [49 (8.45%)]. Imaging of patients who had sepsis showed staghorn calculi [30 (51.72%)] with mild [20 (34.48%)] and moderate [23 (39.66%)] seen on imaging. Patients who were requiring transfusion post operatively (Grade II Clavien-Dindo Classification) were seen to have sepsis.

CONCLUSION

The following factors are contributory to the development of sepsis: a high Guy's stone score, high degree of obstruction or hydronephrosis, previous stone surgery and a higher volume of blood loss.

Human ; Nephrolithotomy, Percutaneous ; Sepsis ; Hydronephrosis

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

OBJECTIVES: Global epidemiological data indicate that 20% to 30% of intensive care unit (ICU) sepsis patients progress to deep vein thrombosis (DVT) due to coagulopathy, with an associated mortality rate of 25% to 40%. Existing prognostic tools have limitations. This study aims to develop and validate nomogram and machine learning models to predict in-hospital mortality in sepsis patients with DVT and assess their clinical applicability. METHODS: This multicenter retrospective study drew on data from the Medical Information Mart for Intensive Care IV (MIMIC-IV; n=2 235), the eICU Collaborative Research Database (eICU-CRD; n=1 274), and the Patient Admission Dataset from the ICU of Third Xiangya Hospital, Central South University (CSU-XYS-ICU; n=107). MIMIC-IV was split into a training set (n=1 584) and internal validation set (n=651), with the remaining datasets used for external validation. Predictors were selected via least absolute shrinkage and selection operator (LASSO) regression and Bayesian Information Criterion (BIC), and a nomogram model was constructed. An extreme gradient boosting (XGBoost) algorithm was used to build the machine learning model. Model performance was assessed by the concordance index (C-index), calibration curves, Brier score, decision curve analysis (DCA), and net reclassification improvement index (NRI). RESULTS: Five key predictors, age [odds ratio (OR)=1.02, 95% CI 1.01 to 1.03, P<0.001], minimum activated partial thromboplastin (APTT; OR=1.09, 95% CI 1.08 to 1.11, P<0.001), maximum APTT (OR=1.01, 95% CI 1.00 to 1.01, P<0.001), maximum lactate (OR=1.56, 95% CI 1.39 to 1.75, P<0.001), and maximum serum creatinine (OR=2.03, 95% CI 1.79 to 2.30, P<0.001), were included in the nomogram. The model showed robust performance in internal validation (C-index=0.845, 95% CI 0.811 to 0.879) and external validation (eICU-CRD: C-index=0.827, 95% CI 0.800 to 0.854; CSU-XYS-ICU: C-index=0.779, 95% CI 0.687 to 0.871). Calibration curves indicated good agreement between predicted and observed outcomes (Brier score<0.25), and DCA confirmed clinical benefit. The XGBoost model achieved an area under the receiver operating characteristic curve (AUC) of 0.982 (95% CI 0.969 to 0.985) in the training set, but performance declined in external validation (eICU-CRD, AUC=0.825, 95% CI 0.817 to 0.861; CSU-XYS-ICU, AUC=0.766, 95% CI 0.700 to 0.873), though it remained above clinical thresholds. Net reclassification improvement was slightly lower for XGBoost compared with the nomogram (NRI=0.58). CONCLUSIONS Both the nomogram and XGBoost models effectively predict in-hospital mortality in sepsis patients with DVT. However, the nomogram offers superior generalizability and clinical usability. Its visual scoring system provides a quantitative tool for identifying high-risk patients and implementing individualized interventions.
Humans ; Sepsis/complications* ; Machine Learning ; Nomograms ; Venous Thrombosis/complications* ; Retrospective Studies ; Hospital Mortality ; Male ; Female ; Middle Aged ; Aged ; Intensive Care Units ; Prognosis ; Bayes Theorem

OBJECTIVES: This study aims to describe the clinical characteristics, treatment received and outcome of patients diagnosed with HLH at the Philippine Children’s Medical Center from 2004 to 2017.

MATERIALS AND METHODS: This cross-sectional analytical study was conducted from June 10, 2023 to June 1, 2024 at the Philippine Children's Medical Center. Detailed information was obtained for each case according to protocol. A complete history was taken from the accompanying caretakers. Children aged 0 to 7 years and 11 months, recently diagnosed with focal epilepsy, were evaluated using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5-TR) criteria. The level of early child development was determined based on the total Battelle Developmental Inventory-2 developmental quotient score.

RESULTS: The study examined 246 children with focal epilepsy. Significant findings included those children with NDD had a higher median age (4.67 years) compared to those without NDD (3.37 years) (p < .001). A higher proportion of non-NDD children were under one year old. Children without NDD had mothers with higher educational attainment (p = .015) and came from families with higher incomes (p = .003). Neonatal complications such as hypoxic-ischemic encephalopathy (HIE) and sepsis were more common in children with NDD (p = .005 and p = .006). Phenobarbital use was more frequent in children with NDD (p = .001), who also had more abnormal EEG and neuroimaging findings (p < .001). Neurodevelopmental evaluations were conducted later for children with NDD (p < .001). A significant number (75.20%) of children exhibited neurodevelopmental problems, with global developmental delay being most prevalent. Crude analysis showed associations between age, number of antiseizure medications, and delays in evaluation with increased odds of NDD.

CONCLUSIONS: The study offers insights into children with focal epilepsy at a tertiary hospital in the Philippines, emphasizing the impact of low socioeconomic status, age, birth complications and multiple anti-seizure medications. These findings are vital for clinicians to modify care plans through a multidisciplinary approach to enhance outcomes and improve quality of life in this high-risk population.

Human ; Male ; Female ; Infant Newborn: First 28 Days After Birth ; Infant: 1-23 Months ; Child Preschool: 2-5 Yrs Old ; Child: 6-12 Yrs Old ; Neurodevelopmental Disorders ; Sepsis ; Hypoxia-ischemia, Brain ; Epilepsies, Partial ; Educational Status ; Diagnostic And Statistical Manual Of Mental Disorders ; Child Development

INTRODUCTION

Neonatal sepsis is a significant cause of morbidity and mortality, particularly among preterm infants, and remains a pressing global health concern. Early-onset neonatal sepsis is particularly challenging to diagnose due to its nonspecific clinical presentation, necessitating effective and timely diagnostic tools to reduce adverse outcomes. Traditional methods, such as microbial cultures, are slow and often unavailable in resource-limited settings. This study aimed to develop a robust multivariable risk prediction model tailored to improve early detection of Early Onset Sepsis (EOS) among preterm infants in the Philippines.

METHODS

We conducted a retrospective analysis at a tertiary hospital in the Philippines using data from 1,354 preterm infants admitted between January 2019 and June 2024. Logistic regression models were employed, and predictors were selected through reverse stepwise elimination. Two scoring methods were developed: one based on beta coefficients divided by standard errors and another standardized to a total score of 100. The models were validated using Receiver Operator Characteristic curve analysis.

RESULTS

Version 1 of the scoring model demonstrated an Area Under the Curve (AUC) of 0.991, with a sensitivity of 90.91% and a specificity of 98.10%. Version 2 achieved an AUC of 0.999, with a sensitivity of 96.4% and a specificity of 92.44%.

CONCLUSIONS

The developed models provide a reliable, region specific tool for early detection of neonatal sepsis. Further validation across diverse populations and the integration of emerging diagnostic technologies, such as biomarkers and artificial intelligence, are warranted to enhance their applicability and accuracy.

Human ; Bacteria ; Infant: 1-23 Months ; Neonatal Sepsis ; Logistic Models ; Infant, Premature ; Philippines

BACKGROUND

Sepsis is a life-threatening organ dysfunction in response to an infection, and immediate administration of the first antibiotic dose, along with other resuscitative efforts, improves patient outcomes. This paved the way for the development of evidence-based sepsis pathways in different health institutions.

OBJECTIVES

This study aims to assess the process of initial antibiotic therapy, from the time the loading dose of antibiotic was ordered to the time it was administered, for adult patients with sepsis admitted at the Emergency Department (ED) of the University of the Philippines – Philippine General Hospital (UP-PGH).

METHODS

In phase 1 of the study, a review of medical records was done to identify all adult patients diagnosed with sepsis in the ED from February 1 to August 31, 2022. A variant of time-motion analysis was used wherein three points in the sepsis pathway were identified: the t ime of diagnosis of sepsis/first chart order of antibiotics (point A), the time the chart order was noted by the nurse-in-charge (point B), and the documented time of f irst dose administration (point C). The mean and median duration (in hours) were then computed between these points. As an additional aim, we briefly presented the outcome of the population used. In phase 2, individual interviews and focused group discussions were done, involving key medical personnel in the sepsis pathway: physicians, nurses, pharmacists, and utility personnel. The data transcribed from these interviews was analyzed through a thematic examination.

RESULTS

A total of 508 adult patients were diagnosed with sepsis on record review, 442 of whom met the inclusion criteria. The median time it took for the nursein-charge to acknowledge the antibiotic order (points A to B) is 0.73 hours (IQR 0.27-1.7). Meanwhile, the median time between acknowledgment of the order to administration of antibiotics is 1.94 hours (IQR 0.83-6.63). More importantly, the median time from diagnosis-to-first dose (points A to C) is 3.53 hours (IQR 1.59–7.96), while the corresponding mean duration is 5.72 hours. In all cases, 44.6% and 12.4% of loading doses were given within three hours and within one hour after diagnosis, respectively. The all-cause mortality of all qualified cases was 64.7%. A total of 28 key medical personnel were recruited for phase 2. Issues regarding governance, information systems, finances, service delivery, and human resources were identified. In particular, the electronic chart system, a more stable supply of antibiotics, and the new pharmacy at the ER helped facilitate antibiotic delivery. Lack of personnel, gaps in information, and repetitive paperwork were cited as areas for improvement in the existing system.

CONCLUSION

In more than half of the study population, the target time from diagnosis to loading dose of at least 1 hour was not reached. The significant delays in sepsis treatment call for system-wide improvements to hasten the process of antibiotic delivery and reduce the poor outcomes associated with sepsis.

Human ; Sepsis

BACKGROUND: Immunosuppression is closely related to the pathogenesis of sepsis, but the underlying mechanisms have not yet been fully elucidated. In this study, we aimed to examine the role of the Sterile Alpha Motif, Src Homology 3 domain and nuclear localization signal 1 (SAMSN1) in sepsis and elucidate its potential molecular mechanism in sepsis induced immunosuppression. METHODS: RNA sequencing databases were used to validate SAMSN1 expression in sepsis. The impact of SAMSN1 on sepsis was verified using gene knockout mice. Flow cytometry was employed to delineate how SAMSN1 affects immunity in sepsis, focusing on immune cell types and T cell functions. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing in RAW264.7 macrophages enabled interrogation of SAMSN1 's regulatory effects on essential macrophage functions, including cell proliferation and phagocytic capacity. The mechanism of SAMSN1 in the interaction between macrophages and T cells was investigated using the RAW264.7 cell line and primary cell lines. RESULTS: SAMSN1 expression was significantly increased in patients with sepsis and was positively correlated with sepsis mortality. Genetic deletion of Samsn1 in murine sepsis model improved T cell survival, elevated T cell cytolytic activity, and activated T cell signaling transduction. Concurrently, Samsn1 knockout augmented macrophage proliferation capacity and phagocytic efficiency. In macrophage, SAMSN1 binds to Kelch-like epichlorohydrin-associated protein 1 (KEAP1), causing nuclear factor erythroid 2-related factor 2 (NRF2) to dissociate from the KEAP1-NRF2 complex and translocate into the nucleus. This promotes the transcription of the coinhibitory molecules CD48/CD86/carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), which bind to their corresponding receptors natural killer cell receptor 2B4/CD152/T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) on the surface of T cells, inducing T-cell exhaustion. CONCLUSIONS SAMSN1 deletion augmented adaptive T cell immunity and macrophage phagocytic-proliferative dual function. Furthermore, it mediates the KEAP1-NRF2 axis, which affects the expression of coinhibitory molecules on macrophages, leading to T-cell exhaustion. This novel immunosuppression mechanism potentially provides a candidate molecular target for sepsis immunotherapy.
Animals ; NF-E2-Related Factor 2/metabolism* ; Mice ; Macrophages/immunology* ; Sepsis/metabolism* ; Kelch-Like ECH-Associated Protein 1/genetics* ; T-Lymphocytes/immunology* ; Humans ; Signal Transduction/physiology* ; RAW 264.7 Cells ; Mice, Knockout ; Mice, Inbred C57BL ; Male ; Flow Cytometry ; T-Cell Exhaustion

This study aims to explore the mechanism of Huanglian Jiedu Decoction(HJD) in treating acute liver injury(ALI) in the mouse model of sepsis induced by lipopolysaccharide(LPS). Fifty-four male C57BL/6 mice were randomized into six groups: blank group, model group, low-, medium-, and high-dose group HJD, and dexamethasone group. The mouse model of sepsis was established by intraperitoneal injection of LPS after 7 days of gavage with HJD, and dexamethasone(0.2 mL) was injected intraperitoneally 1.5 h after modeling. The murine sepsis score(MSS) was recorded 12 h after modeling. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver tissue and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum were measured by ELISA. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the mouse liver. The content of light chain 3 of microtubule-associated protein 1(LC3) was detected by immunofluorescence, and that of sirtuin 1(SIRT1) was detected by immunohistochemistry. The mRNA levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), LC3, and P62 were detected by RT-PCR. Western blot was employed to determine the protein levels of AMPK, p-AMPK, and SIRT1 in the liver tissue. The results showed that compared with model group, drug interventions decreased the MSS and liver injury indicators, lowered the levels of inflammatory cytokines, improved the liver tissue structure, upregulated the protein levels of of p-AMPK/AMPK and SIRT1 and the mRNA levels of AMPK and LC3, and downregulated the mRNA level of P62. To sum up, HJD can regulate the autophagy level and reduce inflammation to ameliorate acute liver injury in septic mice by activating the AMPK/SIRT1 autophagy pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Sirtuin 1/genetics* ; Male ; Mice ; Sepsis/metabolism* ; Mice, Inbred C57BL ; Autophagy/drug effects* ; AMP-Activated Protein Kinases/genetics* ; Liver/metabolism* ; Humans ; Signal Transduction/drug effects* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/genetics*

Simiao Yong'an Decoction is derived from the New Compilation of Proved Prescriptions(Yan Fang Xin Bian). This formula has the effects of clearing heat and detoxifying as well as activating blood and relieving pain. It is mainly used to treat gangrene caused by excessive heat toxin and with the clinical manifestations including dark red and slightly swollen limbs, scorching skin, ulceration and odor, severe pain, occasional fever, thirst, red tongue, and rapid pulse. Nowadays, Simiao Yong'an Decoction is mostly used in the treatment of thromboangitis obliterans, ulcers in arteriosclerosis obliterans of lower limbs, stent restenosis after angioplasty of lower limbs, ecthyma, deep venous thrombosis, diabetic arteriosclerosis obliterans of lower limbs, diabetic foot ulcer, acute knee arthritis, varicose veins of lower limbs, coronary heart disease, post percutaneous coronary intervention(PCI), sepsis, gout, tumor, chronic tonsillitis in children, and other diseases. It has been identified that diabetic foot with infection, sepsis, arteriosclerosis obliterans, and thromboangitis obliterans belong to the category of gangrene in traditional Chinese medicine(TCM), and Simiao Yong'an Decoction is an ancient specialized prescription for treating this disease. The diseases that can be treated by Simiao Yong'an Decoction include arteriosclerosis obliterans, thromboangitis obliterans, diabetic foot, and ecthyma. The symptoms that can be treated by Simiao Yong'an Decoction include dark red, blackened, slightly swollen, burning, ulceration, and odor in the fingers and toes, and toes falling off, hands and feet decaying and collapsing, severe and unbearable pain in some cases. Furthermore, this formula is effective for skin ulceration spreading, pus dripping, swollen and proliferating lymph nodes. These symptoms are always accompanied by dry mouth, thirst, irritability, yellow urine, and dry stool. The TCM symptoms include red tongue, thin and white tongue coating, and wiry and rapid pulse. In the case with the complication of refractory hypotension, large dosage of Astragali Radix is used to replenish Qi, reinforce healthy Qi, and expressing toxin, which can often achieve blood pressure-elevating and anti-inflammatory effects. Simiao Yong'an Decoction is often combined with Simiao Pills and Guizhi Fuling Pills. High-dose medication is the key to the effectiveness of this formula. Integrated traditional Chinese and western medicine plays an important role in the treatment of diabetic foot with infection, sepsis, septic shock, arteriosclerosis obliterans, and thromboangitis obliterans.
Humans ; Diabetic Foot/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; Arteriosclerosis Obliterans/physiopathology* ; Sepsis/physiopathology* ; Critical Care ; Male ; Infections/physiopathology*