OBJECTIVE

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

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.

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.

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.

Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

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*

This study aims to investigate the mechanism by which resveratrol(RES) alleviates cerebral vascular endothelial damage in sepsis-associated encephalopathy(SAE) through network pharmacology and animal experiments. By using network pharmacology, the study identified common targets and genes associated with RES and SAE and constructed a protein-protein interaction( PPI) network. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed to pinpoint key signaling pathways, followed by molecular docking validation. In the animal experiments, a cecum ligation and puncture(CLP) method was employed to induce SAE in mice. The mice were randomly assigned to the sham group, CLP group, and medium-dose and high-dose groups of RES. The sham group underwent open surgery without CLP, and the CLP group received an intraperitoneal injection of 0. 9% sodium chloride solution after surgery. The medium-dose and high-dose groups of RES were injected intraperitoneally with 40 mg·kg-1 and 60 mg·kg~(-1) of RES after modeling, respectively, and samples were collected 12 hours later. Neurological function scores were assessed, and the wet-dry weight ratio of brain tissue was detected. Serum superoxide dismutase(SOD), catalase( CAT) activity, and malondialdehyde( MDA) content were measured by oxidative stress kit. Histopathological changes in brain tissue were examined using hematoxylin-eosin(HE) staining. Transmission electron microscopy was employed to evaluate tight cell junctions and mitochondrial ultrastructure changes in cerebral vascular endothelium. Western blot analysis was performed to detect the expression of zonula occludens1( ZO-1), occludin, claudins-5, optic atrophy 1( OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), fission 1(Fis1), and hypoxia-inducible factor-1α(HIF-1α). Network pharmacology identified 76 intersecting targets for RES and SAE, with the top five core targets being EGFR, PTGS2, ESR1, HIF-1α, and APP. GO enrichment analysis showed that RES participated in the SAE mechanism through oxidative stress reaction. KEGG enrichment analysis indicated that RES participated in SAE therapy through HIF-1α, Rap1, and other signaling pathways. Molecular docking results showed favorable docking activity between RES and key targets such as HIF-1α. Animal experiment results demonstrated that compared to the sham group, the CLP group exhibited reduced nervous reflexes, decreased water content in brain tissue, as well as serum SOD and CAT activity, and increased MDA content. In addition, the CLP group exhibited disrupted tight junctions in cerebral vascular endothelium and abnormal mitochondrial morphology. The protein expression levels of Drp1, Fis1, and HIF-1α in brain tissue were increased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were decreased. In contrast, the medium-dose and high-dose groups of RES showed improved neurological function, increased water content in brain tissue and SOD and CAT activity, and decreased MDA content. Cell morphology in brain tissue, tight junctions between endothelial cells, and mitochondrial structure were improved. The protein expressions of Drp1, Fis1, and HIF-1α were decreased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were increased. This study suggested that RES could ameliorate cerebrovascular endothelial barrier function and maintain mitochondrial homeostasis by inhibiting oxidative stress after SAE damage, potentially through modulation of the HIF-1α signaling pathway.
Animals ; Mice ; Network Pharmacology ; Resveratrol/administration & dosage* ; Male ; Sepsis-Associated Encephalopathy/genetics* ; Signal Transduction/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Endothelium, Vascular/metabolism* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Humans ; Sepsis/complications* ; Oxidative Stress/drug effects*

Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

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.

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.

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%.

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.

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.

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).

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.

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.

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.

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*

OBJECTIVE: To analyze the clinical characteristics of elderly patients with sepsis, identify the key factors affecting their clinical outcomes, construct a death risk assessment scale for elderly patients with sepsis, and evaluate its predictive value. METHODS: A retrospective case-control study was conducted. The clinical data of sepsis patients admitted to intensive care unit (ICU) of the First Affiliated Hospital of Wenzhou Medical University from September 2021 to September 2023 were collected, including basic information, clinical characteristics, and clinical outcomes. The patients were divided into non-elderly group (age ≥ 65 years old) and elderly group (age < 65 years old) based on age. Additionally, the elderly patients were divided into survival group and death group based on their 30-day survival status. The clinical characteristics of elderly patients with sepsis were analyzed. Univariate and multivariate Logistic regression analyses were used to screen the independent risk factors for 30-day death in elderly patients with sepsis, and the regression equation was constructed. The regression equation was simplified, and the death risk assessment scale was established. The predictive value of different scores for the prognosis of elderly patients with sepsis was compared. RESULTS: (1) A total of 833 patients with sepsis were finally enrolled, including 485 in the elderly group and 348 in the non-elderly group. Compared with the non-elderly group, the elderly group showed significantly lower counts of lymphocyte, T cell, CD8⁺ T cell, and the ratio of T cells and CD8⁺ T cells [lymphocyte count (×10⁹/L): 0.71 (0.43, 1.06) vs. 0.83 (0.53, 1.26), T cell count (cells/μL): 394.0 (216.0, 648.0) vs. 490.5 (270.5, 793.0), CD8⁺ T cell count (cells/μL): 126.0 (62.0, 223.5) vs. 180.0 (101.0, 312.0), T cell ratio: 0.60 (0.48, 0.70) vs. 0.64 (0.51, 0.75), CD8⁺ T cell ratio: 0.19 (0.13, 0.28) vs. 0.24 (0.16, 0.34), all P < 0.01], higher natural killer cell (NK cell) count, acute physiology and chronic health evaluation II (APACHE II) score, ratio of invasive mechanical ventilation (IMV) during hospitalization, and 30-day mortality [NK cell count (cells/μL): 112.0 (61.0, 187.5) vs. 95.0 (53.0, 151.0), APACHE II score: 16.00 (12.00, 21.00) vs. 13.00 (8.00, 17.00), IMV ratio: 40.6% (197/485) vs. 31.9% (111/348), 30-day mortality: 28.9% (140/485) vs. 19.5% (68/348), all P < 0.05], and longer length of ICU stay [days: 5.5 (3.0, 10.0) vs. 5.0 (3.0, 8.0), P < 0.05]. There were no statistically significant differences in the levels of inflammatory markers such as C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukins (IL-2, IL-4, IL-6, IL-10) between the two groups. (2) In 485 elderly patients with sepsis, 345 survived in 30 days, and 140 died with the 30-day mortality of 28.9%. Compared with the survival group, the patients in the death group were older, and had lower body mass index (BMI), white blood cell count (WBC), PCT, platelet count (PLT) and higher IL-6, IL-10, N-terminal pro-brain natriuretic peptide (NT-proBNP), total bilirubin (TBil), blood lactic acid (Lac), and ratio of in-hospital IMV and continuous renal replacement therapy (CRRT). Multivariate Logistic regression analysis indicated that BMI [odds ratio (OR) = 0.783, 95% confidence interval (95%CI) was 0.678-0.905, P = 0.001], IL-6 (OR = 1.073, 95%CI was 1.004-1.146, P = 0.036), TBil (OR = 1.009, 95%CI was 1.000-1.018, P = 0.045), Lac (OR = 1.211, 95%CI was 1.072-1.367, P = 0.002), and IMV during hospitalization (OR = 6.181, 95%CI was 2.214-17.256, P = 0.001) were independent risk factors for 30-day death in elderly patients with sepsis, and the regression equation was constructed (Logit P = 1.012-0.244×BMI+0.070×IL-6+0.009×TBil+0.190×Lac+1.822×IMV). The regression equation was simplified to construct a death risk assessment scale, namely BITLI score. Receiver operator characteristic curve (ROC curve) analysis showed that the area under the ROC curve (AUC) of BITLI score for predicting death risk was 0.852 (95%CI was 0.769-0.935), and it was higher than APACHE II score (AUC = 0.714, 95%CI was 0.623-0.805) and sequential organ failure assessment (SOFA) score (AUC = 0.685, 95%CI was 0.578-0.793). The determined cut-off value of BITLI score was 1.50, while achieving a sensitivity of 83.3% and specificity of 74.0%. CONCLUSIONS Elderly patients with sepsis often have reduced lymphocyte counts, severe conditions, and poor prognosis. BMI, IL-6, TBil, Lac, and IMV during hospitalization were independent risk factors for 30-day death in elderly patients with sepsis. The BITLI score constructed based above risk factors is more precise and reliable than traditional APACHE II and SOFA scores in predicting the outcomes of elderly patients with sepsis.
Humans ; Sepsis/mortality* ; Aged ; Retrospective Studies ; Risk Assessment ; Case-Control Studies ; Prognosis ; Male ; Female ; Intensive Care Units ; Risk Factors ; Aged, 80 and over ; Logistic Models ; Middle Aged