As a grave and highly lethal clinical challenge, sepsis, along with its consequent multiorgan dysfunction, affects millions of people worldwide. Sepsis is a complex syndrome caused by a dysregulated host response to infection, leading to fatal organ dysfunction. An increasing body of evidence suggests that the pathogenesis of sepsis is both intricate and rapid and involves various cellular responses and signal transductions mediated by post-translational modifications (PTMs). Hence, a comprehensive understanding of the mechanisms and functions of PTMs within regulatory networks is imperative for understanding the pathological processes, diagnosis, progression, and treatment of sepsis. In this review, we provide an exhaustive and comprehensive summary of the relationship between PTMs and sepsis-induced organ dysfunction. Furthermore, we explored the potential applications of PTMs in the treatment of sepsis, offering a forward-looking perspective on the understanding of infectious diseases.

The COVID-19 pandemic, which is caused by the SARS-CoV-2 virus, has resulted in extensive health challenges globally. While SARS-CoV-2 primarily targets the respiratory system, clinical studies have revealed that it could also affect multiple organs, including the heart, kidneys, liver, and brain, leading to severe complications. To unravel the intricate molecular interactions between the virus and host tissues, we performed an integrated transcriptomic analysis to investigate the effects of SARS-CoV-2 on various organs, with a particular focus on the relationship between renal failure and COVID-19. A comparative analysis showed that SARS-CoV-2 triggers a systemic immune response in the brain, heart, and kidney tissues, characterized by significant upregulation of cytokine and chemokine secretion, along with enhanced migration of lymphocytes and leukocytes. A weighted gene co-expression network analysis demonstrated that SARS-CoV-2 could also induce tissue-specific transcriptional profiling. More importantly, single-cell sequencing revealed that COVID-19 patients with renal failure exhibited lower metabolic activity in lung epithelial and B cells, with reduced ligand-receptor interactions, especially CD226 and ICAM, suggesting a compromised immune response. A trajectory analysis revealed that COVID-19 patients with renal failure exhibited less mature alveolar type 1 cells. Furthermore, these patients showed potential fibrosis in the hearts, liver, and lung increased extracellular matrix remodeling activities. However, there was no significant metabolic dysregulation in the liver of COVID-19 patients with renal failure. Candidate drugs prediction by Drug Signatures database and LINCS L1000 Antibody Perturbations Database underscored the importance of considering multi-organ effects in COVID-19 management and highlight potential therapeutic strategies, including targeting viral entry and replication, controlling tissue fibrosis, and alleviating inflammation.

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Background: Destructive aortic prosthetic valve endocarditis portends a high morbidity and mortality, and requires complex high-risk surgery. Homograft root replacement is the most radical and biocompatible operation and, thus, the preferred option. Methods: A retrospective analysis was conducted on 61 consecutive patients who underwent a cardiac reoperation comprising homograft aortic root replacement since 2010. The probabilities of survival were calculated with the Kaplan-Meier method, whereas multivariable regression served to outline the predictors of adverse events. The endpoints were operative/late death, perioperative low cardiac output and renal failure, and reoperations. Results: The operative (cumulative hospital and 30-day) mortality was 13%. The baseline aspartate transaminase (AST) and associated mitral procedures were predictive of operative death (p = 0.048, OR [95% CIs] = 1.03 [1-1.06]) and perioperative low cardiac output, respectively (p = 0.04, OR [95% CIs] = 21.3 [2.7-168.9] for valve replacement). The latter occurred in 12 (20%) patients, despite a normal ejection fraction. Survival estimates (±SE) at 3 months, 6 months, 1 year, and 3 years after surgery were 86.3 ± 4.7%, 82.0 ± 4.9%, 75.2 ± 5.6, and 70.0 ± 6.3%, respectively. Survival was significantly lower in the case of AST ≥ 40 IU/L (p = 0.04) and aortic cross-clamp time ≥ 180 min (p = 0.01), but not when excluding operative survivors. Five patients required early (two out of the five, within 3 months) or late (three out of the five) reoperation. Conclusions: Homograft aortic root replacement for destructive prosthetic valve endocarditis can currently be performed with a near 90% operative survival and reasonable 3-year mortality and reoperation rate. AST might serve to additionally stratify the operative risk.

Systemic inflammation generally coexists with functional limitations that seriously affect quality of life. This study aimed to investigate the association between systemic inflammation in midlife and the risk of functional limitations in late-life. A total of 10,044 participants with an average age of 53.9 ± 5.7 years at baseline were included in a cohort study. At the last follow-up, the prevalence of impaired activities of daily living (ADLs), instrumental activities of daily living (IADLs), and lower extremity function (LEF) was 14.7%, 21.6%, and 50.3%, respectively. The values of four inflammatory biomarkers were used to calculate the inflammation composite score. Compared with the participants in the lowest quartile of the inflammation composite score (Q1), those in the highest quartile (Q4) exhibited an odds ratio (OR) of 1.589 and a 95% confidence interval (CI) of 1.335-1.892 for impaired ADLs, an OR of 1.426 and a 95% CI of 1.228-1.657 for impaired IADLs, and an OR of 1.728 and a 95% CI of 1.526-1.957 for impaired LEF. The association between systemic inflammation and functional limitations was partly mediated by cardiac and brain function. The present study provides evidence that systemic inflammation in midlife is associated with a higher risk of late-life functional limitations. Protecting vital organ functions in midlife may have a positive impact on reducing the risk of future functional limitations.Trial registration: www.clinicaltrials.gov ; Unique identifier: NCT00005131.

OBJECTIVE: Early diagnosis and prediction of organ dysfunction are critical for intervening and improving the outcomes of septic patients. The study aimed to find novel diagnostic and predictive biomarkers of organ dysfunction for perioperative septic patients.
METHODS: This is a prospective, controlled, preliminary, and single-center study of emergency surgery patients. Mass spectrometry, Gene Ontology (GO) functional analysis, and the protein-protein interaction (PPI) network were performed to identify the differentially expressed proteins (DEPs) from sepsis patients, which were selected for further verification via enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to estimate the relative correlation of selected serum protein levels and clinical outcomes of septic patients. Calibration curves were plotted to assess the calibration of the models.
RESULTS: Five randomized serum samples per group were analyzed via mass spectrometry, and 146 DEPs were identified. GO functional analysis and the PPI network were performed to evaluate the molecular mechanisms of the DEPs. Six DEPs were selected for further verification via ELISA. Cathepsin B (CatB), vascular cell adhesion protein 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL), protein S100-A9, prosaposin, and thrombospondin-1 levels were significantly increased in the patients with sepsis compared with those of the controls (p < 0.001). Logistic regression analysis showed that CatB, S100-A9, VCAM-1, prosaposin, and NGAL could be used for preoperative diagnosis and postoperative prediction of organ dysfunction. CatB and S100-A9 were possible predictive factors for preoperative diagnosis of renal failure in septic patients. Internal validation was assessed using the bootstrapping validation. The preoperative diagnosis of renal failure model displayed good discrimination with a C-index of 0.898 (95% confidence interval 0.843-0.954) and good calibration.
CONCLUSIONS: Serum CatB, S100-A9, VCAM-1, prosaposin, and NGAL may be novel markers for preoperative diagnosis and postoperative prediction of organ dysfunction. Specifically, S100-A9 and CatB were indicators of preoperative renal dysfunction in septic patients. Combining these two biomarkers may improve the accuracy of predicting preoperative septic renal dysfunction.
BACKGROUND: The study was registered at the Chinese Clinical Trials Registry (ChiCTR2200060418) on June 1, 2022.

Patients admitted to a pediatric intensive care unit (PICU) need individualized nutrition support that is tailored to their particular disease severity, nutritional status, and therapeutic interventions. We aim to evaluate how calories and proteins are provided during the first seven days of hospitalization for children in critical condition with organ dysfunction (OD). A single-center retrospective cohort study of children aged 2-18 years, mechanically ventilated > 48 h, and admitted > 7 days to a PICU from 2016 to 2017 was carried out. Nutrition support included enteral and parenteral nutrition. We calculated scores for the Pediatric Sequential Organ Failure Assessment (pSOFA) on days 1 and 3 of admission, with OD defined as a score > 5. Of 4199 patient admissions, 164 children were included. The prevalence of OD for days 1 and 3 was 79.3% and 78.7%, respectively. On day 3, when pSOFA scores trended upward, decreased, or remained unchanged, median (IQR) caloric intake was 0 (0-15), 9.2 (0-25), and 22 (1-43) kcal/kg/day, respectively (p = 0.0032); when pSOFA scores trended upward, decreased, or remained unchanged, protein intake was 0 (0-0.64), 0.44 (0-1.25), and 0.66 (0.04-1.67) g/kg/day, respectively (p = 0.0023). Organ dysfunction was prevalent through the first 72 h of a PICU stay. When the pSOFA scores trended downward or remained unchanged, caloric and protein intakes were higher than those that trended upward.

Tissue hypoxia is associated with the development of organ dysfunction and death in critically ill patients commonly captured using blood lactate. The kinetic parameters of serial lactate evaluations are superior at predicting mortality compared with single values. S-adenosylhomocysteine (SAH), which is also associated with hypoxia, was recently established as a useful predictor of septic organ dysfunction and death. We evaluated the performance of kinetic SAH parameters for mortality prediction compared with lactate parameters in a cohort of critically ill patients. For lactate and SAH, maxima and means as well as the normalized area scores were calculated for two periods: the first 24 h and the total study period of up to five days following ICU admission. Their performance in predicting in-hospital mortality were compared in 99 patients. All evaluated parameters of lactate and SAH were significantly higher in non-survivors compared with survivors. In univariate analysis, the predictive power for mortality of SAH was higher compared with lactate in all forms of application. Multivariable models containing SAH parameters demonstrated higher predictive values for mortality than models based on lactate parameters. The optimal models for mortality prediction incorporated both lactate and SAH parameters. Compared with lactate, SAH displayed stronger predictive power for mortality in static and dynamic application in critically ill patients.

This study aimed to investigate the incidence and significance of disseminated intravascular coagulation (DIC) in coronavirus disease 2019 (COVID-19). A multicenter cohort study was conducted using large-scale COVID-19 registry data. The patients were classified into DIC and non-DIC groups based on the diagnosis on admission (day 1) and on any of the days 1, 4, 8, and 15. In total, 23,054 patients were divided into DIC (n = 264) and non-DIC (n = 22,790) groups on admission. Thereafter, 1654 patients were divided into 181 patients with DIC and 1473 non-DIC patients based on the DIC diagnosis on any of the days from 1 to 15. DIC incidence was 1.1% on admission, increasing to 10.9% by day 15. DIC diagnosis on admission had moderate predictive performance for developing multiple organ dysfunction syndrome (MODS) on day 4 and in-hospital death and was independently associated with MODS and in-hospital death. DIC diagnosis on any of the days from 1 to 15, especially days 8 and 15, was associated with lower survival probability than those without DIC and showed significant association with in-hospital death. In conclusion, despite its low incidence, DIC, particularly late-onset DIC, plays a significant role in the pathogenesis of poor prognosis in patients with COVID-19.

BACKGROUND: It is important to determine the prevalence and prognosis of community-acquired infection (CAI) and nosocomial infection (NI) to develop treatment strategies and appropriate medical policies in aging society.
METHODS: Patients hospitalized between January 2010 and December 2019, for whom culture tests were performed and antibiotics were administered, were selected using a national claims-based database. The annual trends in incidence and in-hospital mortality were calculated and evaluated by dividing the patients into four age groups.
RESULTS: Of the 73,962,409 inpatients registered in the database, 9.7% and 4.7% had CAI and NI, respectively. These incidences tended to increase across the years in both the groups. Among the patients hospitalized with infectious diseases, there was a significant increase in patients aged ≥ 85 years (CAI: + 1.04%/year and NI: + 0.94%/year, P < 0.001), while there was a significant decrease in hospitalization of patients aged ≤ 64 years (CAI: -1.63%/year and NI: -0.94%/year, P < 0.001). In-hospital mortality was significantly higher in the NI than in the CAI group (CAI: 8.3%; NI: 14.5%, adjusted mean difference 4.7%). The NI group had higher organ support, medical cost per patient, and longer duration of hospital stay. A decreasing trend in mortality was observed in both the groups (CAI: -0.53%/year and NI: -0.72%/year, P < 0.001).
CONCLUSIONS: The present analysis of a large Japanese claims database showed that NI is a significant burden on hospitalized patients in aging societies, emphasizing the need to address particularly on NI.