Juntendo University Shizuoka Hospital

Sepsis is now considered a dysregulated host response in which inflammation, coagulation, and endothelial injury converge to create a self-amplifying network of thromboinflammation. This definition reflects maladaptive immunothrombosis-a defense mechanism that becomes pathogenic when excessive, rather than an isolated inflammatory process. This review integrates recent mechanistic advances linking damage-associated molecular patterns (DAMPs), endothelial dysfunction, and intravascular coagulation. Endogenous alarmins, such as high-mobility group box 1, histones, and mitochondrial DNA, engage in pattern recognition (Toll-like receptors, receptor for advanced glycation end products) to propagate leukocyte activation, platelet aggregation, and endothelial disruption. The resulting loss of critical endothelial anticoagulant molecules (thrombomodulin, endothelial cell protein C receptor, antithrombin) and glycocalyx degradation convert the vascular endothelium into a procoagulant interface. Complement activation and protease-activated receptor signaling reinforce this loop, producing microvascular thrombosis, capillary leakage, and organ ischemia. Platelet-leukocyte aggregates and neutrophil extracellular traps (NETs) serve as intravascular scaffolds for fibrin deposition, thereby propagating disseminated intravascular coagulation (DIC). Targeted interventions, including recombinant thrombomodulin, antithrombin supplementation, neutralization of NETs and DAMPs, complement blockade, and endothelial-protective strategies, seek to restore vascular homeostasis. A multidomain biomarker approach integrating DAMPs, endothelial markers, and coagulation indices, combined with machine learning-based phenotyping, may enable precision stratification of sepsis endotypes. The convergence of DAMP signaling, immune activation, and coagulation underlies the pathophysiologic continuum from sepsis-induced coagulopathy to DIC. Therapeutically interrupting this axis represents the most promising avenue toward personalized, mechanism-driven treatment in sepsis.

To identify the clinical factors associated with independence in activities of daily living (ADL) at discharge in patients with spinal cord dysfunction resulting from metastatic spinal tumors. Retrospective cohort study. A single university hospital in Japan. A total of 153 patients (N=153) (median age 69 [interquartile range: 58.5-75.5]; 67% men) with spinal cord dysfunction caused by metastatic spinal tumors received inpatient rehabilitation during hospitalization between 2012 and 2022. The inclusion criteria were age ≥18 years, a diagnosis of spinal cord dysfunction resulting from metastatic bone tumors, and participation in inpatient rehabilitation. Participants underwent standard inpatient rehabilitation care. No study-specific intervention was provided. Independence in ADL was defined as a Barthel index score of ≥85 at discharge. Data on demographics, clinical characteristics, and potential risk factors were extracted from medical records. Logistic regression analysis, adjusted for age, was conducted to identify predictors of independence in ADL at discharge. Among the participants, 23 (15.0%) achieved independence in ADL at discharge. Logistic regression analysis identified the following 4 significant factors associated with reduced odds of independence in ADL: rapid-growing primary tumor type (odds ratio [OR]=5.93; 95% CI, 1.81-19.43), severe motor impairment at admission (OR=5.83; 95% CI, 1.89-18.00), elevated C-reactive protein/albumin ratio (OR=3.82; 95% CI, 1.53-17.80), and persistent movement-related pain (OR=1.34; 95% CI, 1.01-1.84). Tumor aggressiveness, neurologic severity, systemic inflammation, and persistent pain significantly influenced independence in ADL at discharge. Early identification of these risk factors may guide individualized rehabilitation planning and optimize functional outcomes in this population.

Abstract Background Both lipoprotein(a) (Lp[a]) and C-reactive protein (CRP) have been reported as risk factors of cardiovascular events in patients with coronary artery disease. Purpose The aim of the present study is to evaluate the impact of combined Lp(a) and CRP levels for future cardiovascular events in acute myocardial infarction (AMI) patients. Methods We retrospectively investigated 2,425 consecutive patients with AMI who underwent percutaneous coronary intervention in our institution from January 2004 to December 2017. We finally enrolled 1,152 patients for whom Lp(a) and CRP were available and who were discharged alive. Patients were assigned to 4 groups according to their median Lp(a) and CRP levels (15 mg/100ml and 0.30 mg/dL, respectively). The primary endpoints were major adverse cardiac or cerebrovascular events (MACCEs), including cardiovascular death, MI and stroke between 30 days to 3 years after AMI. Results During median follow-up period of 2.5 years, 78 cases of MACCEs (6.7%) were identified. The rates of MACCE significantly differed among the groups (log-rank test, p=0.0007) and patients in both high Lp(a) and CRP group had clearly higher incidence of MACCE compared with other group patients. After adjustment for established risk factors, high Lp(a) with high CRP level was significantly associated with MACCE (hazard risk 2.58, 95% confidence interval 1.32-5.04, p=0.006, both low Lp(a) and CRP group as reference). Conclusions The presence of both high Lp(a) and CRP level conferred a synergistic adverse effect on the risk for recurrence cardiovascular events in following AMI.

Abstract Background Ischemic preconditioning has been associated with smaller infarct size and better clinical outcomes in patients with acute myocardial infarction (AMI). However, the association between pre-angina and long-term clinical outcomes after AMI is uncertain. Purpose The present study aimed to evaluate the impact of pre-angina on long-term cardiovascular outcomes in AMI patients. Methods Consecutive AMI patients who underwent primary percutaneous intervention between 1999 and 2015 were retrospectively analyzed. The primary endpoint was cardiovascular death up-to 5 years. We divided patients into two groups based on whether they had angina prior to the onset of AMI. Results Of the 2,159 AMI patients who had available information of prior symptoms, 1,101 patients (51.0%) had pre-angina. Patients without pre-angina were older and higher rate of ST elevated MI (STEMI). 30-day cardiovascular mortality was significantly higher in patients without pre-angina compared those with pre-angina among both STEMI and NSTEMI patients. Landmark Kaplan-Meier analysis showed that cardiovascular mortality after 30-day was significantly higher in patients without pre-angina among STEMI population, however, the cumulative incidence of cardiovascular death was not significantly different between two groups among NSTEMI population. Conclusions Absence of chest symptoms before AMI is associated with poor prognosis. Especially for STEMI patients, it is associated with both short- and long-term cardiovascular mortality.30-day cardiovascular mortality Land-mark analysis for cardiovascular de

Abstract Introduction Cardiogenic shock (CS) remains the leading cause of death in patients with acute coronary syndrome (ACS) despite advances in medical therapy and revascularization strategies. Previous studies showed conflicting views on the off-hours effect on mortality, and limited data exist especially concerning ACS complicated by CS. Purpose This study aimed to evaluate the effect of on-hours versus off-hours presentation on the clinical outcomes in ACS patients with and without CS. Methods We retrospectively analyzed 2,425 consecutive ACS patients who underwent percutaneous coronary intervention (PCI) at our institution between January 2004 and December 2017. We divided patients in on-hours and off-hours groups and further stratified them by cardiogenic shock. The primary outcome was cardiovascular (CV) death up to 3-year, assessed by a 30-day landmark analysis. Results Among the 2,312 eligible ACS patients, 1,572 were admitted during on-hours and 740 during off-hours. The mean age was 68.5±12.0 years, 75.3 % were male, and ST-elevation myocardial infarction (STEMI) was observed in 75.3 % of cases. Notably, the 30-day CV mortality of off-hours group was significantly higher in ACS patients with CS (24.8 % vs 39.0 %, log-rank P = 0.0232) but not in those without CS(log rank P = 0.98). The CV mortality from 30 days to 3 years was comparable in both patients with and without CS. Multivariate Cox regression analysis showed off-hours presentation was significantly associated with higher risk of the 30-day CV mortality in ACS patients with CS (adjusted HR 1.65, 95%CI 1.16-3.16, log-rank P= 0.0110). Conclusions Off-hours presentation was significantly associated with higher risk of short-term CV death especially in ACS patients with cardiogenic shock. Further investigation and targeted efforts are necessary to improve the prognosis and off-hour medical care in high-risk patients.Figure1 (Study Flow Chart) Figure2 (Landmark analysis)

Uterine artery embolization is a treatment option for symptomatic uterine myomas. The Japanese Society of Interventional Radiology Guideline Committee developed guidelines for uterine artery embolization procedures for symptomatic uterine myomas using an evidence-based methodology. This report describes the rationale for developing these guidelines and provides answers to clinical questions concerning uterine artery embolization procedures based on existing evidence and expert consensus.

ObjectiveTo clarify the disease pattern for elderly individuals in the general population in Japan with multimorbidity networks based on an analysis of common chronic conditions.Patients and MethodsThis study is a population study of disease network analysis in elderly in Japan. We obtained medical records for 4,797,907 elderly patients in Japan (from January 1, 2020 to December 31, 2020) from administrative claim databases. The administrative claim records were transformed for temporal disease occurrence pattern analysis and used to find frequently occurring disease sequences to predict the onset of disease progression.ResultsIn those aged 75 years and older, circulatory and respiratory diseases gained predominance, while the burden of mental disorders remained substantial across all age groups. In men aged below 75 years, disseminated intravascular coagulation co-occurred frequently with acute myocardial infarction and respiratory failure. In women aged below 75 years, the pairing of vestibular dysfunction and hearing loss exhibited the highest association. For women aged 75 years and older, renal disease pairings, psychiatric comorbidities, and fall-related injuries were dominant. Network analyses reported increasing multimorbidity complexity with age. Respiratory, circulatory, and digestive disease clusters were central across age groups, with psychiatric and fracture-related conditions becoming more prominent in older adults, particularly women. Disease heatmaps further highlighted systemic comorbidity hubs involving pneumonia, iron deficiency anemia, kidney disease, and cardiovascular conditions.ConclusionIn this study, we identified major comorbidity patterns and reported that atherosclerosis, angina pectoris, gastritis, and duodenitis were the most important comorbid diseases in the elderly population in Japan. The identification of distinctive comorbidity profiles from routine clinical data provides insights that may be leveraged to improve diagnosis and identify treatment targets for patients.