Objective: Many studies have examined the July effect. However, little is known about the July effect in sepsis. We hypothesized that the July effect would result in worse outcomes for patients with sepsis. Methods: Data from patients with sepsis, collected prospectively between January 2018 and December 2021, were analyzed. In Korea, the new academic year starts on March 1, so the “July effect” appears in March. The primary outcome was 30-day mortality. Secondary outcomes included adherence to the Surviving Sepsis Campaign bundle. Outcomes in March were compared to other months. A multivariate Cox proportional hazard regression was performed to adjust for confounders. Results: We included 843 patients. There were no significant differences in sepsis severity. The 30-day mortality in March was higher (49.0% vs. 28.5%, P<0.001). However, there was no difference in bundle adherence in March (42.2% vs. 48.0%, P=0.264). The multivariate Cox proportional hazard regression showed that the July effect was associated with 30-day mortality in patients with sepsis (adjusted hazard ratio, 1.925; 95% confidence interval, 1.405–2.638; P<0.001). Conclusion The July effect was associated with 30-day mortality in patients with sepsis. However, bundle adherence did not differ. These results suggest that the increase in mortality during the turnover period might be related to unmeasured in-hospital management. Intensive supervision and education of residents caring for patients with sepsis is needed in the beginning of training.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a common cause of autoimmune encephalitis. The condition is difficult to diagnose or suspect in the emergency department because it usually presents with nonspecific neurological or psychiatric symptoms. It is often mistaken for viral encephalitis or psychiatric illness. This paper reports a case of anti-NMDAR encephalitis in which the patient experienced mood changes, including suicidal ideation, which led to a delayed diagnosis after three visits to the emergency department. This paper aims to raise awareness among emergency physicians about the possibility of anti-NMDAR encephalitis and to encourage them to consider it in their differential diagnosis in the emergency department.

Patients undergoing hemodialysis are susceptible to sarcopenia. As intracellular reservoirs of water, skeletal muscles are important contributors to intradialytic hypotension. This study was designed to determine the role of skeletal muscle mass in intradialytic hypotension. Methods: In a cross-sectional study, the body composition of 177 patients was measured immediately after hemodialysis using bioelectrical impedance analysis. The parameters measured were skeletal muscle mass, intracellular and extracellular water contents, total body water, and cell-membrane functionality (in phase angle at 50 kHz). Data from laboratory tests, chest radiography, measurements of handgrip strength and mid-arm circumference, and questionnaires were collected. The main outcome was intradialytic hypotension, defined as more than two episodes of hypotension (systolic blood pressure of <90 mmHg) with intervention over the 3 months following enrollment. Logistic regression models including each parameter related to sarcopenia were compared with a clinical model. Results: Patients with a low ratio of skeletal muscle mass to dry body weight (SMM/WT) had a higher rate of intradialytic hypotension (40.7%). Most low-SMM/WT patients were female, obese, diabetic, and had a lower handgrip strength compared with the other patients. In the high-SMM/WT group, the risk of intradialytic hypotension was lower, with an odds ratio of 0.08 (95% confidence interval [CI], 0.02–0.28) and adjusted odds ratio of 0.06 (95% CI, 0.01–0.29). Conclusion: Measurement and maintenance of skeletal muscle can help prevent intradialytic hypotension in frail patients undergoing hemodialysis.

Objective: The Surviving Sepsis Campaign (SSC) guidelines have been associated with reduced mortality in sepsis patients. On the other hand, previous studies were performed using the Sepsis-2 definitions and past guidelines. This study assessed the association between compliance with the 2016 SSC guidelines and the outcomes of patients with sepsis and septic shock in accordance with the latest Sepsis-3 definitions. Methods: Three hundred and fifteen patients with sepsis and septic shock were enrolled in this study. The patients were stratified according to their compliance with the SSC guidelines bundle. The characteristics and outcomes of the compliance and non-compliance groups were compared. In the overall patients, the risk factors for all-cause mortality were assessed using Cox proportional hazards models. Results: Among the patients, 172 and 143 patients were in the compliance group and non-compliance group, respectively. The baseline characteristics and disease severity were similar in the two groups. The all-cause mortality rates were 27.3% and 38.5% in the compliance group and non-compliance group, respectively (P=0.035). The all-cause mortality was significantly lower in the compliance group than in the non-compliance group (log-rank test, P=0.025). The risk factors for the all-cause mortality were age (adjusted hazard ratio [aHR], 1.025; 95% confidence interval [CI], 1.008-1.042; P=0.004), septic shock (aHR, 3.14; 95% CI, 1.98-4.98; P<0.001), and lactate levels (aHR, 1.08; 95% CI, 1.03-1.14; P=0.002). The overall compliance with the guidelines protected against all-cause mortality (aHR, 0.66; 95% CI, 0.45-0.98; P=0.040). Conclusion Compliance with the SSC guidelines bundle was associated with a lower all-cause mortality among patients with sepsis and septic shock

BACKGROUND: Unlike patterns observed in the general population, obesity is associated with better survival among hemodialysis patients, which could be explained by reverse causation or illness-related weight loss. However, the time-varying effect of body mass index (BMI) on hemodialysis survival has not been investigated. Therefore, this study investigated the time-varying effect of BMI on mortality after starting hemodialysis. METHODS: In the present study, we examined Korean Society of Nephrology data from 16,069 adult patients who started hemodialysis during or after the year 2000. Complete survival data were obtained from Statistics Korea. Survival analysis was performed using Cox regression and a non-proportional hazard fractional polynomial model. RESULTS: During the median follow-up of 8.6 years, 9,272 patients (57.7%) died. Compared to individuals with normal BMI (18.5–24.9 kg/m²), the underweight group (< 18.5 kg/m²) had a higer mortality hazard ratio (HR, 1.292; 95% confidence interval [CI], 1.203–1.387; P < 0.001) and the overweight group (25.0–29.9 kg/m²) had a lower mortality HR (0.904; 95% CI, 0.829–0.985; P = 0.022). The underweight group had increasing HRs during the first 3 to 7 years after starting hemodialysis, which varied according to age group. The young obese group (< 40 years old) had a U-shaped temporal trend in their mortality HRs, which reflected increased mortality after 7 years. CONCLUSION: The obese hemodialysis group had better survival during the early post-dialysis period, although the beneficial effect of obesity disappeared 7 years after starting hemodialysis. The young obese group also had an increased mortality HR after 7 years.
Adult ; Body Mass Index ; Follow-Up Studies ; Humans ; Korea ; Models, Statistical ; Mortality ; Nephrology ; Obesity ; Overweight ; Renal Dialysis ; Thinness ; Weight Loss

Few studies have reported on the long-term prognosis of anti-neutrophil cytoplasmic antibody (ANCA)-negative renal vasculitis. Between April 2003 and December 2013, 48 patients were diagnosed with renal vasculitis. Their ANCA status was tested using indirect immunofluorescence and enzyme-linked immunosorbent assays. During a median (interquartile range) follow-up duration of 933.5 (257.5-2,079.0) days, 41.7% of patients progressed to end stage renal disease (ESRD) and 43.8% died from any cause. Of 48 patients, 6 and 42 were ANCA-negative and positive, respectively. The rate of ESRD within 3 months was higher in ANCA-negative patients than in ANCA-positive patients (P = 0.038). In Kaplan-Meier survival analysis, ANCA-negative patients showed shorter renal survival than did ANCA-positive patients (log-rank P = 0.033). In univariate Cox-proportional hazard regression analysis, ANCA-negative patients showed increased risk of ESRD, with a hazard ratio 3.190 (95% confidence interval, 1.028-9.895, P = 0.045). However, the effect of ANCA status on renal survival was not statistically significant in multivariate analysis. Finally, ANCA status did not significantly affect patient survival. In conclusion, long-term patient and renal survival of ANCA-negative renal vasculitis patients did not differ from those of ANCA-positive renal vasculitis patients. Therefore, different treatment strategy depending on ANCA status might be unnecessary.
Age Factors ; Aged ; Antibodies, Antineutrophil Cytoplasmic/*analysis ; Cohort Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Kidney Diseases/*diagnosis/mortality ; Kidney Failure, Chronic/etiology ; Male ; Microscopy, Fluorescence ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Sex Factors ; Vasculitis/complications/*diagnosis/mortality

Echocardiographic parameters can predict cardiovascular events in several clinical settings. However, which echocardiographic parameter is most predictive of each cardiovascular or non-cardiovascular event in patients starting hemodialysis remains unresolved. Echocardiography was used in 189 patients at the time of starting hemodialysis. We established primary outcomes as follows: cardiovascular events (ischemic heart disease, cerebrovascular disease, peripheral artery disease, and acute heart failure), fatal non-cardiovascular events, all-cause mortality, and all combined events. The most predictable echocardiographic parameter was determined in the Cox hazard ratio model with a backward selection after the adjustment of multiple covariates. Among several echocardiographic parameters, the E/e' ratio and the left ventricular end-diastolic volume (LVEDV) were the strongest predictors of cardiovascular and non-cardiovascular events, respectively. After the adjustment of clinical and biochemical covariates, the predictability of E/e' remained consistent, but LVEDV did not. When clinical events were further analyzed, the significant echocardiographic parameters were as follows: s' for ischemic heart disease and peripheral artery disease, LVEDV and E/e' for acute heart failure, and E/e' for all-cause mortality and all combined events. However, no echocardiographic parameter independently predicted cerebrovascular disease or non-cardiovascular events. In conclusion, E/e', s', and LVEDV have independent predictive values for several cardiovascular and mortality events.
*Echocardiography ; Female ; Heart Failure/*diagnosis/mortality ; Humans ; Kidney Failure, Chronic/mortality/*therapy ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; *Renal Dialysis ; Risk Factors ; Ventricular Function, Left/*physiology

We aimed to elucidate the effect of bilirubin on dyslipidemia and nephropathy in a diabetes mellitus (DM) type I animal model. Sprague-Dawley rats were separated into control, DM, and bilirubin-treated DM (Bil) groups. The Bil group was injected intraperitoneally with 60 mg/kg bilirubin 3 times per week and hepatoma cells were cultured with bilirubin at a concentration of 0.3 mg/dL. The Bil group showed lower serum creatinine levels 5 weeks after diabetes onset. Bilirubin treatment also decreased the amount of mesangial matrix, lowered the expression of renal collagen IV and transforming growth factor (TGF)-beta1, and reduced the level of apoptosis in the kidney, compared to the DM group. These changes were accompanied by decreased tissue levels of hydrogen superoxide and NADPH oxidase subunit proteins. Bilirubin decreased serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), free fatty acids, and triglycerides (TGs), as well as the TG content in the liver tissues. Bilirubin suppressed protein expression of LXRalpha, SREBP-1, SCD-1, and FAS, factors involved in TG synthesis that were elevated in the livers of DM rats and hepatoma cells under high-glucose conditions. In conclusion, bilirubin attenuates renal dysfunction and dyslipidemia in diabetes by suppressing LXRalpha and SREBP-1 expression and oxidative stress.
Animals ; Bilirubin/pharmacology/*therapeutic use ; Cell Line, Tumor ; Creatine/blood ; Diabetes Mellitus, Experimental/chemically induced/complications/*pathology ; Diabetic Nephropathies/*drug therapy/etiology ; Disease Models, Animal ; Kidney/pathology ; Lipoproteins, HDL/blood ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; NADPH Oxidase/metabolism ; Orphan Nuclear Receptors/antagonists & inhibitors/genetics/metabolism ; Oxidative Stress/drug effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Streptozocin/toxicity ; Triglycerides/analysis/*biosynthesis/blood

The expression of hypoxia-inducible factor (HIF) is influenced by reactive oxygen species (ROS). Effect of bilirubin on HIF-1 expression in proximal tubular cells was investigated under physiological oxygen concentration, which is relative hypoxic condition mimicking oxygen content in the medulla of renal tissue. The human kidney (HK2) cells were cultured in 5% oxygen with or without bilirubin. HIF-1alpha protein expression was increased by bilirubin treatment at 0.01-0.2 mg/dL concentration. The messenger RNA expression of HIF-1alpha was increased by 1.69+/-0.05 folds in the cells cultured with 0.1 mg/dL bilirubin, compared to the control cells. The inhibitors of PI3K/mTOR, PI3K/AKT, and ERK 1/2 pathways did not attenuate increased HIF-1alpha expression by bilirubin. HIF-1alpha expression decreased by 10 microM exogenous hydrogen peroxide (H2O2); scavenger of ROS with or without bilirubin in the HK2 cells increased HIF-1alpha concentration more than that in the cells without bilirubin. Exogenous H2O2 decreased the phosphorylation of P70S6 kinase, which was completely reversed by bilirubin treatment. Knockdown of NOX4 gene by small interfering RNA (siRNA) increased HIF-1alpha mRNA expression. In coonclusion, bilirubin enhances HIF-1alpha transcription as well as the up-regulation of HIF-1alpha protein translation through the attenuation of ROS and subunits of NADPH oxidase.
Bilirubin/*pharmacology ; Cell Line ; Epithelial Cells/cytology/metabolism ; Humans ; Hydrogen Peroxide/toxicity ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Kidney Tubules, Proximal/cytology ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; NADPH Oxidase/antagonists & inhibitors/genetics/metabolism ; Oxygen/*pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Ribosomal Protein S6 Kinases, 70-kDa/metabolism ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/metabolism ; Transcriptional Activation/*drug effects ; Up-Regulation/drug effects

It is not well described the pathophysiology of renal injuries caused by a high salt intake in humans. The authors analyzed the relationship between the 24-hr urine sodium-to-creatinine ratio (24HUna/cr) and renal injury parameters such as urine angiotensinogen (uAGT/cr), monocyte chemoattractant peptide-1 (uMCP1/cr), and malondialdehyde-to-creatinine ratio (uMDA/cr) by using the data derived from 226 hypertensive chronic kidney disease patients. At baseline, the 24HUna/cr group or levels had a positive correlation with uAGT/cr and uMDA/cr adjusted for related factors (P<0.001 for each analysis). When we estimated uAGT/cr in the 24HUna/cr groups by ANCOVA, the uAGT/cr in patients with > or =200 mEq/g cr was higher than in patients with <100 mEq/g cr (708 [95% CI, 448-967] vs. 334 [95% CI, 184-483] pg/mg cr, P=0.014). Similarly, uMDA/cr was estimated as 0.17 (95% CI, 0.14-0.21) pM/mg cr in patients with <100 mEq/g cr and 0.27 (95% CI, 0.20-0.33) pM/mg cr in patients with > or =200 mEq/g cr (P=0.016). During the 16-week follow-up period, an increase in urinary sodium excretion predicted an increase in urinary angiotensinogen excretion. In conclusion, high salt intake increases renal renin-angiotensin-system (RAS) activation, primarily, and directly or indirectly affects the production of reactive oxygen species through renal RAS activation.
Adult ; Aged ; Angiotensinogen/urine ; Chemokine CCL2/urine ; Creatine/urine ; Demography ; Female ; Follow-Up Studies ; Humans ; Hypertension/complications ; Male ; Malondialdehyde/urine ; Middle Aged ; Reactive Oxygen Species/*metabolism ; Renal Insufficiency, Chronic/complications/*pathology ; Renin-Angiotensin System/*physiology ; Sodium, Dietary/*urine ; Urine Specimen Collection