History of fragility fracture is associated with cardiovascular mortality in hemodialysis patients: the Q-Cohort study.

INTRODUCTION: In patients undergoing dialysis, major bone fracture is associated with a high risk of mortality, including death of cardiovascular (CV) origin. In the present study, we aimed to determine whether a history of fragility fracture is a predictor of CV death in patients undergoing hemodialysis with long-term follow-up. MATERIALS AND METHODS: In total, 3499 patients undergoing hemodialysis were analyzed for 10 years. We evaluated the history of fragility fracture in each patient at enrollment. The primary outcome was CV death. A Cox proportional hazard model and a competing risk approach were applied to determine the association between a history of fragility fracture and CV death. RESULTS: A total of 346 patients had a history of fragility fracture at enrollment. During a median follow-up of 8.8 years, 1730 (49.4%) patients died. Among them, 621 patients experienced CV death. Multivariable Cox analyses after adjustment for confounding variables showed that a history of fragility fracture was associated with CV death (hazard ratio, 1.47; 95% confidence interval, 1.16-1.85). In the Fine-Gray regression model, a history of fragility fracture was an independent risk factor for CV death (subdistribution hazard ratio, 1.36; 95% confidence interval, 1.07-1.72). CONCLUSION: In a large cohort of patients undergoing hemodialysis, a history of fragility fracture was an independent predictor of CV death.

Sex differences in the association between urate metabolism and kidney outcomes in patients with chronic kidney disease.

BACKGROUND: The association between serum uric acid (SUA) concentration and kidney outcomes in patients with chronic kidney disease (CKD) is controversial. Furthermore, there are no reports regarding the association of clearance of uric acid (CUA) with kidney outcomes. We aimed to determine whether SUA or CUA was associated with kidney outcomes in patients with CKD stratified by sex. METHODS: The present prospective study was conducted in 815 patients (523 men and 292 women) with CKD. The participants were divided into quartiles (Q1-Q4) of SUA or CUA for each sex. Endpoints were defined as a composite of doubling of serum creatinine (SCr), end-stage kidney disease (ESKD), or death (outcome 1) and a composite of doubling of SCr or ESKD (outcome 2). RESULTS: During a median follow-up of 2.5 years, outcomes 1 and 2 occurred in 363 and 321 patients, respectively. Multivariable-adjusted Cox analyses showed that in men, the hazard ratios (95% confidence intervals) for outcome 1 of Q1, Q2, and Q3 of CUA were 2.08 (1.18-3.70), 2.03 (1.22-3.39), and 1.85 (1.17-2.95), respectively, compared with Q4. Additionally, there were similar associations between lower CUA quartiles and outcome 2 in men. However, no associations between SUA and either outcome were observed in men. Conversely, in women, neither SUA nor CUA was associated with an outcome. CONCLUSION: In CKD, lower CUA was independently associated with poor kidney outcomes only in men, and in both sexes, there was no association of SUA with kidney outcomes.

Development and external validation of the DOAT and DOATS scores: simple decision support tools to identify disease progression among nonelderly patients with mild/moderate COVID-19.

BACKGROUND: During the fifth wave of the coronavirus disease 2019 (COVID-19) pandemic in Japan, which took place between June and September 2021, a significant number of COVID-19 cases with deterioration occurred in unvaccinated individuals < 65 years old. However, the risk factors for COVID-19 deterioration in this specific population have not yet been determined. This study developed a prediction method to identify COVID-19 patients < 65 years old who are at a high risk of deterioration. METHODS: This retrospective study analyzed data from 1,675 patients < 65 years old who were admitted to acute care institutions in Fukushima with mild-to-moderate-1 COVID-19 based on the Japanese disease severity criteria prior to the fifth wave. For validation, 324 similar patients were enrolled from 3 hospitals in Yamagata. Logistic regression analyses using cluster-robust variance estimation were used to determine predictors of disease deterioration, followed by creation of risk prediction scores. Disease deterioration was defined as the initiation of medication for COVID-19, oxygen inhalation, or mechanical ventilation starting one day or later after admission. RESULTS: The patients whose condition deteriorated (8.6%) tended to be older, male, have histories of smoking, and have high body temperatures, low oxygen saturation values, and comorbidities, such as diabetes/obesity and hypertension. Stepwise variable selection using logistic regression to predict COVID-19 deterioration retained comorbidities of diabetes/obesity (DO), age (A), body temperature (T), and oxygen saturation (S). Two predictive scores were created based on the optimism-corrected regression coefficients: the DOATS score, including all of the above risk factors, and the DOAT score, which was the DOATS score without oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve (AUROCs) of the DOATS and DOAT scores were 0.81 (95% confidence interval [CI] 0.77-0.85) and 0.80 (95% CI 0.76-0.84), respectively. In the validation cohort, the AUROCs for each score were both 0.76 (95% CI 0.69-0.83), and the calibration slopes were both 0.80. A decision curve analysis confirmed the clinical practicability of both scores in the validation cohort. CONCLUSIONS: We established two prediction scores that can quickly evaluate the risk of COVID-19 deterioration in mild/moderate patients < 65 years old.

Real-world clinical outcomes of treatment with casirivimab-imdevimab among patients with mild-to-moderate coronavirus disease 2019 during the Delta variant pandemic.

Background: Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan. Methods: We enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635). Results: The casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature (≥ 38°C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263-0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021). Conclusion: This real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge.

Low plasma renin activity is independently associated with kidney disease progression in patients with type 2 diabetes and overt nephropathy, including those with impaired kidney function: a 2-year prospective study.

Plasma renin activity (PRA) is lower in patients with diabetic nephropathy (DN) than in healthy individuals. However, the association, if any, between PRA and renal outcomes in patients with DN remains uncertain. In a 2-year prospective observational study, we aimed to investigate the association of PRA with the decline in kidney function in patients with DN. We studied 97 patients with DN who were categorized according to tertile (T1-T3) of PRA. The annual changes in estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2/year) were determined from the slope of the linear regression curve for eGFR. The secondary endpoint was defined as a composite of the doubling of serum creatinine or end-stage renal disease. Results showed that kidney function rapidly declined with lower tertiles of PRA (median value [interquartile range] of the annual eGFR changes: -8.8 [-18.5 to -4.2] for T1, -8.0 [-14.3 to -3.2] for T2, and -3.1 [-6.3 to -2.0] for T3; p for trend <0.01). Multivariable linear regression analyses showed that, compared with T3, T1 was associated with a larger annual change in eGFR (coefficient, -4.410; 95% confidence interval [CI], -7.910 to -0.909 for T1). Composite renal events occurred in 46 participants. In multivariable Cox analysis, the lower tertiles of PRA (T1 and T2) were associated with higher incidences of the composite renal outcome (T2: hazard ratio [HR], 4.78; 95% CI, 1.64-13.89; T1: HR, 4.85; 95% CI 1.61-14.65) than T3. In conclusion, low PRA is independently associated with poor renal outcomes in patients with DN.

Association between urinary salt excretion and albuminuria in Japanese patients with chronic kidney disease: the Fukuoka kidney disease registry study.

BACKGROUND: Several large population-based studies have demonstrated that urinary salt excretion (USALT) is associated with albuminuria. However, this relationship has not been assessed in a large cohort study of patients with chronic kidney disease (CKD). Thus, the present study aimed to elucidate whether USALT was independently associated with albuminuria in a large cohort of patients with CKD. METHODS: This cross-sectional study was conducted in 4075 patients with CKD not on dialysis. USALT (g/day) was estimated from spot urine. Patients were divided into quartiles (Q1-Q4) according to estimated USALT. Multivariable regression models were used to determine whether USALT was independently related to urinary albumin-to-creatinine ratio (UACR) or the presence of macroalbuminuria. RESULTS: In multivariable linear regression analyses, 1-g/day increment in USALT was significantly associated with log UACR [coefficient 0.098, 95% confidence interval (CI) 0.075-0.121]. In addition, compared with the first USALT quartile, the third and fourth quartiles exhibited significant associations with log UACR (Q3: coefficient 0.305, 95% CI 0.154-0.456; Q4: coefficient 0.601, 95% CI 0.447-0.756). Furthermore, multivariable logistic regression analyses showed that USALT (1-g/day increment) was significantly associated with the presence of macroalbuminuria [odds ratio (OR) 1.11, 95% CI 1.07-1.14]; the third and fourth USALT quartiles exhibited significantly greater risks of macroalbuminuria, compared with the first quartile (Q3: OR 1.33, 95% CI 1.09-1.62; Q4: OR 1.89, 95% CI 1.54-2.32). CONCLUSIONS: This significant association of USALT with UACR and macroalbuminuria suggests that higher USALT may cause increased albuminuria, thereby contributing to kidney disease progression.

Association of aortic valve calcification with carotid artery lesions and peripheral artery disease in patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Patients with chronic kidney disease (CKD) reportedly have a high prevalence of aortic valve calcification (AVC). In population-based studies, AVC is considered a manifestation of systemic atherosclerosis. The association of AVC with atherosclerotic lesions has not been fully investigated in predialysis patients. The present study was performed to determine whether carotid artery lesions and peripheral artery disease (PAD) are associated with AVC in patients with CKD not on dialysis. METHODS: In total, 749 patients were included in this cross-sectional study. AVC was evaluated using echocardiography. Carotid artery lesions including carotid artery plaque (CAP) and PAD were simultaneously examined in each patient. A logistic regression analysis was applied to determine the factors associated with AVC. RESULTS: AVC, CAP, and PAD were found in 201, 583, and 123 patients, respectively. In the multivariable analyses adjusted for covariates including the estimated glomerular filtration rate and makers of mineral metabolism (serum calcium, serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23), AVC was significantly associated with the presence of CAP [odds ratio (OR), 3.37; 95% confidence interval (CI), 1.43-7.95], the presence of PAD (OR, 1.76; 95% CI, 1.10-2.81), the CAP score (per 1.0-point increase) (OR, 1.06; 95% CI, 1.02-1.11), and the ankle-brachial blood pressure index (per 0.1-point increase) (OR, 0.83; 95% CI, 0.72-0.95). CONCLUSIONS: AVC was associated with atherosclerotic lesions independent of kidney function and mineral metabolism. We consider that this association between AVC and atherosclerosis might reflect the burden of shared atherosclerotic risk factors.

Blood urea nitrogen is independently associated with renal outcomes in Japanese patients with stage 3-5 chronic kidney disease: a prospective observational study.

BACKGROUND: Blood urea nitrogen (BUN) is one of the substances that affects the calculated serum osmolality (cSosm). A previous study demonstrated that BUN and cSosm were independently associated with the development of chronic kidney disease (CKD) in patients with preserved kidney function. In advanced CKD stages, there is a concomitant increase in cSosm and BUN levels. However, it remains unclear whether BUN or cSosm levels are related to renal outcomes in patients with moderate to severe kidney dysfunction. The aim of this study was to clarify whether the BUN or cSosm level is associated with kidney disease progression in patients with advanced CKD. METHODS: In this prospective study, we enrolled 459 patients with CKD (stages 3-5). The composite renal endpoint was end-stage renal disease (ESRD) or death, and ESRD alone was added as an alternative outcome. A Cox proportional hazards model was utilized to determine the risk factors for a poor renal outcome. We adjusted for covariates including estimated glomerular filtration rate (eGFR). The cSosm (mOsm/kg) was calculated using the following formula: (2 × sodium) + (BUN/2.8) + (glucose/18). RESULTS: During a median follow-up of 25.8 months, the renal endpoint was observed in 210 patients. Multivariable Cox analysis determined the hazard ratio (HR) [95% confidence interval (CI)] for the composite renal outcome in the second, third, and fourth BUN quartiles were 1.36 (0.72-2.58), 1.87 (0.95-3.66), and 2.66 (1.23-5.76) (P for trend < 0.01), respectively compared with the first BUN quartile. Conversely, by multivariable Cox analysis, the HRs (95% CIs) for poor outcomes in the second, third, and fourth cSosm quartiles, compared with the first cSosm quartile, were 1.13 (0.69-1.87), 0.95 (0.58-1.55), and 1.26 (0.78-2.03), respectively (P for trend = 0.39). In addition, with regard to the renal outcome of ESRD alone, higher BUN quartiles had a significantly increased risk for the outcome, but cSosm levels were not associated with the outcome. CONCLUSIONS: Higher BUN levels, but not cSosm levels, were associated with adverse renal outcomes independent of the eGFR, suggesting that BUN may be a useful marker for predicting kidney disease progression.

High neutrophil/lymphocyte ratio is associated with poor renal outcomes in Japanese patients with chronic kidney disease.

BACKGROUND: Several studies have shown that the neutrophil/lymphocyte ratio (NLR) is a marker that reflects the state of systemic inflammation. A high NLR was reported to be associated with cardiovascular events and mortality. However, little is known about the association between NLR and kidney disease progression in patients with chronic kidney disease (CKD). Therefore, the aim of the present study was to determine whether NLR is associated with renal outcomes in CKD patients. METHODS: This prospective observational study included 350 consecutive patients with stage 1-4 CKD treated between June 2009 and November 2016. Data were collected until June 2017. The endpoint was the composite of end-stage renal disease requiring dialysis or death. Subjects were divided into two groups according to high and low NLR levels. A Cox proportional hazards model was used to determine the risk factors for composite outcomes. RESULTS: The composite endpoint was observed in 83 patients during the median follow-up period of 31.8 months: 29 in the low NLR group and 54 in the high NLR group. Multivariable analysis showed that the high NLR group had a significant increase in the hazard ratio (HR) for composite outcomes (HR 1.67, 95% confidence interval 1.02-2.77) compared with the low NLR group. CONCLUSION: The present study demonstrated that a high NLR was associated with poor renal outcomes, suggesting that NLR may be a useful marker for prognostic prediction in patients with CKD.

Comparison of Prognostic Values of Daytime and Night-Time Systolic Blood Pressures on Renal Outcomes in Patients With Chronic Kidney Disease.

BACKGROUND: Differences in the predictive value of daytime systolic blood pressure (SBP) and night-time SBP by ambulatory blood pressure monitoring on renal outcomes have not been fully investigated in chronic kidney disease (CKD) patients. This study compared the prognostic value between daytime and night-time SBP on renal outcomes in CKD.Methods and Results:This prospective observational study included 421 patients. The composite renal endpoint was endstage renal disease (ESRD) or death. Cox models were used to determine associations of daytime and night-time SBP with renal outcomes. There were 150 renal events (ESRD, 130; death, 20). Multivariable Cox analyses demonstrated that hazard ratios (HRs) [95% confidence interval (CI)] for composite renal outcomes of every 10-mmHg increase in daytime and night-time SBP levels were 1.13 (1.02-1.26) (P=0.02) and 1.15 (1.05-1.27) (P<0.01), respectively. In addition, compared with the 1st daytime or night-time SBP quartile, HRs (95% CI) for outcomes in the 2nd, 3rd, and 4th quartiles were: daytime SBP, 1.25 (0.70-2.25), 1.09 (0.61-1.94), and 1.58 (0.88-2.85; P=0.13) (P for trend=0.16); night-time SBP, 1.09 (0.61-1.96), 1.31 (0.76-2.28), and 1.82 (1.00-3.30; P=0.049) (P for trend=0.03), respectively. CONCLUSIONS: Night-time SBP appeared superior to daytime SBP for predicting renal outcomes in this population of patients.

Human collagen XV is a prominent histopathological component of sinusoidal capillarization in hepatocellular carcinogenesis.

BACKGROUND: Increased expression of collagen XV has been reported in hepatocellular carcinogenesis in mice. The aim of this study was to confirm the previous murine findings in human hepatocellular carcinoma (HCC) specimens, along with the histopathological distribution of collagen XV in tumoral tissues. METHODS: Sixty-three primary HCC specimens were examined. Immunostaining of collagen XV and quantitative reverse transcriptional PCR of COL15A1, which encodes collagen XV, were performed. RESULTS: Positive staining of collagen XV was observed in all tumoral regions, regardless of differentiation level or pathological type of HCC, along the sinusoid-like endothelium, whereas collagen XV was not expressed in any non-tumoral region. The intensity score of collagen XV immunostaining and the mRNA value of COL15A1 were significantly correlated. COL15A1 expression in tumors was 3.24-fold higher than in non-tumoral regions. Multivariate analysis showed that COL15A1 expression was significantly higher in the absence of hepatitis virus and moderately differentiated HCC. CONCLUSIONS: COL15A1 mRNA was up-regulated in HCC and collagen XV was expressed along the sinusoid-like endothelium of HCC but not in non-tumoral regions, which implies that collagen XV contributes to the capillarization of HCC.

A Novel Kidney Failure Prediction Model in Individuals with CKD: Impact of Serum Bilirubin Levels.

CONTEXT: Predicting the progression of chronic kidney disease (CKD) to end-stage kidney disease (ESKD) is crucial for improving patient outcomes. OBJECTIVE: To reveal the highly predictive activity of serum bilirubin levels for the progression of CKD to ESKD, and to develop and validate a novel ESKD prediction model incorporating serum bilirubin levels. METHODS: We assessed the relative importance of 20 candidate predictors for ESKD, including serum bilirubin levels, in a CKD cohort (15< eGFR <60 mL/min/1.73 m2), and subsequently developed a prediction model using the selected variables. The development cohort comprised 4,103 individuals with CKD who underwent follow-up at Kyushu University Hospital, Japan, from 2008 to 2018. The primary outcome was incident ESKD, defined as an eGFR <15 mL/min/1.73 m2, chronic dialysis, or renal transplantation. RESULTS: The mean follow-up time was 7.0 ± 4.2 years, during which 489 individuals (11.9%) progressed to ESKD. The Cox proportional hazard model selected eGFR, serum bilirubin, proteinuria, age, diabetes, gender, hypertension, serum albumin, and hemoglobin in order of their importance. The predictive performance of the model was optimized by incorporating these 9 variables in discrimination evaluated by time-dependent area under the curve (AUC). This model also demonstrated excellent calibration. Additionally, this model exhibited excellent predictive performance in both discrimination (2-year AUC: 0.943, 5-year AUC: 0.935) and calibration in a validation cohort (n=2,799). CONCLUSION: Serum bilirubin levels were strong predictors for the progression of CKD to ESKD. Our novel model that incorporates serum bilirubin levels could accurately predict ESKD in individuals with CKD.

Fibroblast growth factor 23 is associated with carotid artery calcification in chronic kidney disease patients not undergoing dialysis: a cross-sectional study.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is an important hormone in the regulation of phosphate metabolism. It is unclear whether FGF23 is associated with carotid artery calcification (CAAC) in predialysis patients. The present study aimed to clarify the relationship between FGF23 and CAAC in patients with chronic kidney disease (CKD) who were not on dialysis. METHODS: One-hundred ninety-five predialysis CKD patients were enrolled in this cross-sectional study. CAAC was assessed using multidetector computed tomography, and the prevalence of CAAC was examined. Intact FGF23 was measured in each patient. The risk factors for CAAC were evaluated using a logistic regression model. RESULTS: We found CAAC in 66% of the patients. The prevalence of CAAC significantly increased across CKD stages: it was 37% in CKD stages 1-2, 58% in stage 3; 75% in stage 4, and 77% in stage 5 (p < 0.01). In multivariate analysis, smoking, diabetes mellitus and log FGF23 were each identified as risk factors for CAAC. The study population was divided in quartiles of FGF23 levels. Compared with the lowest FGF23 quartile, each subsequent quartile had a progressively higher odds ratio (OR) for CAAC, adjusted for confounders (ORs [95% confidence interval] of 2.34 [0.78 to 7.31], 5.28 [1.56 to 19.5], and 13.6 [2.92 to 74.6] for the second, third, and fourth quartiles, respectively. CONCLUSIONS: The prevalence of CAAC is increased with the decline in the kidney function. FGF23 is independently related to CAAC in patients with CKD who are not on dialysis.

Association between iron status markers and kidney outcome in patients with chronic kidney disease.

Several studies conducted in patients with various stages of chronic kidney disease (CKD) have investigated the association of iron status markers, such as transferrin saturation (TSAT) and serum ferritin, with kidney outcomes. However, the associations were inconsistent and remain strongly debated. Therefore, we aimed to investigate whether TSAT and serum ferritin levels were associated with kidney outcome in such a population. In this study, 890 patients who were admitted for the evaluation of and education for CKD were prospectively followed. Primary kidney outcome was a composite of doubling of serum creatinine, end-stage kidney disease, or death due to kidney failure. Participants were divided into quartiles (Q1-Q4) according to TSAT or serum ferritin levels. During a median follow-up period of 2.8 years, kidney events occurred in 358 patients. In the multivariable Cox analyses, compared with Q3 of TSAT, the hazard ratios (95% confidence intervals) for Q1, Q2, and Q4 were 1.20 (0.87, 1.66), 1.38 (1.01, 1.87), and 1.14 (0.82, 1.59), respectively. Compared with Q2 of serum ferritin, lower and higher quartiles had a significantly increased risk for kidney outcome; hazard ratios (95% confidence intervals) for Q1, Q3, and Q4 were 1.64 (1.18, 2.27), 1.71 (1.24, 2.37), and 1.52 (1.10, 2.10), respectively. A Fine-Gray model with death before kidney events as a competing risk showed results similar to the above. In CKD, lower and higher ferritin levels were independent risk factors for kidney disease progression.

The Association of Controlling Nutritional Status Score and Prognostic Nutritional Index with Cardiovascular Diseases: the Fukuoka Kidney Disease Registry Study.

AIM: The Controlling Nutritional Status (CONUT) score and the Prognostic Nutritional Index (PNI) reflect the immunonutritional status of patients. However, the associations of these two indices with cardiovascular disease (CVD) have not been characterized in patients with chronic kidney disease (CKD). Therefore, the current study aimed to determine whether the CONUT score or PNI was associated with prior CVD in patients with CKD. METHODS: A cross-sectional study of 2,751 patients with CKD who were not on dialysis was performed. The patients were grouped into tertiles (T1-T3) of PNI and placed into three groups following their CONUT score: low- (CONUT score, 0), mild- (CONUT score, 1-2), and moderate-to-high- (CONUT score, ≥ 3) risk groups. RESULTS: Prior CVD was present in 655 (24%) of the participants. Multivariable logistic regression analyses, with adjustment for potential confounders, showed that high CONUT score was associated with prior CVD than the low score (mild-risk group: odds ratio [OR]=1.35, 95% confidence interval [CI]=1.04-1.76; moderate-to-high-risk group: OR=1.66, 95% CI=1.19-2.30). In addition, the lower PNI tertiles were independently associated with prior CVD compared with T3 of PNI (T1: OR=1.45, 95% CI=1.09-1.92; T2: OR=1.32, 95% CI=1.01-1.72). CONCLUSIONS: Both CONUT score and PNI were found to be independently associated with prior CVD in patients with CKD in the present cross-sectional study. A longitudinal study is needed to elucidate whether these two indices are associated with subsequent cardiovascular events.

Real-world clinical outcomes of treatment with molnupiravir for patients with mild-to-moderate coronavirus disease 2019 during the Omicron variant pandemic.

It is unclear whether molnupiravir has a beneficial effect on vaccinated patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We here evaluated the efficacy of molnupiravir in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron variant surge in Fukushima Prefecture, Japan. We enrolled patients with mild-to-moderate COVID-19 who were admitted to hospitals between January and April, 2022. Clinical deterioration after admission was compared between molnupiravir users (n = 230) and non-users (n = 690) after 1:3 propensity score matching. Additionally, we performed forward stepwise multivariate logistic regression analysis to evaluate the association between clinical deterioration after admission and molnupiravir treatment in the 1:3 propensity score-matched subjects. The characteristics of participants in both groups were balanced as indicated by covariates with a standardized mean difference of < 0.1. Regarding comorbidities, there was no imbalance between the two groups, except for the presence of hypertension, dyslipidemia, diabetes mellitus, and cardiac disease. The clinical deterioration rate was significantly lower in the molnupiravir users compared to the non-users (3.90% vs 8.40%; P = 0.034). Multivariate logistic regression analysis demonstrated that receiving molnupiravir was a factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.206-0.973; P = 0.042), independent of other covariates. This real-world study demonstrates that molnupiravir contributes to the prevention of deterioration in COVID-19 patients after hospitalization during the Omicron variant phase.

Dynamic photoswitching of helical inversion in liquid crystals containing photoresponsive axially chiral dopants.

Chirality switching is intriguing for the dynamic control of the electronic and optical properties in nanoscale materials. The ability to photochemically switch the chirality in liquid crystals (LCs) is especially attractive given their potential applications in electro-optic displays, optical data storage, and the asymmetric synthesis of organic molecules and polymers. Here, we present a dynamic photoswitching of the helical inversion in chiral nematic LCs (N*-LCs) that contain photoresponsive axially chiral dopants. Novel photoresponsive chiral dithienylethene derivatives bearing two axially chiral binaphthyl moieties are synthesized. The dihedral angle of the binaphthyl rings changes via the photoisomerization between the open and closed forms of the dithienylethene moiety. The N*-LCs induced by the dithienylethene derivatives that are used as chiral dopants exhibit reversible photoswitching behaviors, including a helical inversion in the N*-LC and a phase transition between the N*-LC and the nematic LC. The present compounds are the first chiral dopants that induce a helical inversion in N*-LC via the photoisomerization between open and closed forms of the dithienylethene moiety.

Predicting the outcome of chronic kidney disease by the estimated nephron number: the rationale and design of PRONEP, a prospective, multicenter, observational cohort study.

BACKGROUND: The nephron number is thought to be associated with the outcome of chronic kidney disease (CKD). If the nephron number can be estimated in the clinical setting, it could become a strong tool to predict renal outcome. This study was designed to estimate the nephron number in CKD patients and to establish a method to predict the outcome by using the estimated nephron number. METHODS/DESIGN: The hypothesis of this study is that the estimated nephron number can predict the outcome of a CKD patient. This will be a multicenter, prospective (minimum 3 and maximum 5 years follow-up) study. The subjects will comprise CKD patients aged over 14 years who have undergone a kidney biopsy. From January 2011 to March 2013, we will recruit 600 CKD patients from 10 hospitals belonging to the National Hospital Organization of Japan. The primary parameter for assessment is the composite of total mortality, renal death, cerebro-cardiovascular events, and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR decline per year. The nephron number will be estimated by the glomerular density in biopsy specimens and the renal cortex volume. This study includes one sub-cohort study to establish the equation to calculate the renal cortex volume. Enrollment will be performed at the time of the kidney biopsy, and the data will consist of a medical interview, ultrasound for measurement of the kidney size, blood or urine test, and the pathological findings of the kidney biopsy. Patients will continue to have medical consultations and receive examinations and/or treatment as usual. The data from the patients will be collected once a year after the kidney biopsy until March 2016. All data using this study are easily obtained in routine clinical practice. DISCUSSION: This study includes the first trials to estimate the renal cortex volume and nephron number in the general clinical setting. Furthermore, this is the first prospective study to examine whether the nephron number predicts the outcome of CKD patients. The results from this study should provide powerful new tools for nephrologists in routine clinical practice. TRIAL REGISTRATION: UMIN-Clinical Trial Registration, UMIN000004784.

Carotid artery calcification at the initiation of hemodialysis is a risk factor for cardiovascular events in patients with end-stage renal disease: a cohort study.

BACKGROUND: Vascular calcification has been recognized as a risk factor for cardiovascular (CV) events in patients with end-stage renal disease (ESRD). However, the association of carotid artery calcification (CAAC) with CV events remains unknown. The aim of this study was to elucidate whether CAAC is associated with composite CV events in ESRD patients. METHODS: One-hundred thirty-three patients who had been started on hemodialysis between 2004 and 2008 were included in this retrospective cohort study. These patients received multi-detector computed tomography to assess CAAC at the initiation of hemodialysis. Composite CV events, including ischemic heart disease, heart failure, cerebrovascular diseases, and CV deaths after the initiation of hemodialysis, were examined in each patient. RESULTS: CAAC was found in 94 patients (71%). At the end of follow-up, composite CV events were seen in 47 patients: ischemic heart disease in 20, heart failure in 8, cerebrovascular disease in 12, and CV deaths in 7. The incidence of CAAC was 87% in patients with CV events, which was significantly higher than the rate (62%) in those without. Kaplan-Meier analysis showed a significant increase in composite CV events in patients with CAAC compared with those without CAAC (p = 0.001, log-rank test). Univariate analysis using a Cox hazards model showed that age, smoking, common carotid artery intima-media thickness and CAAC were risk factors for composite CV events. In multivariate analysis, only CAAC was a significant risk factor for composite CV events (hazard ratio, 2.85; 95% confidence interval, 1.18-8.00; p = 0.02). CONCLUSIONS: CAAC is an independent risk factor for CV events in ESRD patients. The assessment of CAAC at the initiation of hemodialysis is useful for predicting the prognosis.

The effect of low-dose corticosteroids on short- and long-term renal outcome in patients with cholesterol crystal embolism.

BACKGROUND: The effect of corticosteroids on renal cholesterol crystal embolism (CCE) remains uncertain. The aim of the present study was to elucidate the effect of steroid therapy on short- and long-term renal outcome in CCE patients. METHODS: Fifty-one patients diagnosed with renal CCE were included in this retrospective study. The patients were divided into two groups according to whether or not they had received steroid therapy (steroid therapy (+), n = 32; (-), n = 19). Corticosteroids were administered at an initial dose of 10-20 mg/day after CCE diagnosis. The values of the estimated glomerular filtration rate (eGFR) in the two groups were examined at CCE diagnosis, 4 weeks after diagnosis and the last follow-up. Additionally, the % change in eGFR at 4 weeks after diagnosis and % change per year in eGFR at the last follow-up were calculated for each patient. RESULTS: The median values of eGFR at diagnosis in patients with and without steroid therapy were 16.4 and 17.9 mL/min/1.73 m(2), respectively. The median % change in eGFR between diagnosis and 4 weeks after diagnosis was 24% in patients with steroid therapy and 5% in those without, and this difference was statistically significant. On the other hand, there was no significant difference between the two groups in the % change in eGFR per year between diagnosis and the last follow-up. CONCLUSIONS: During the short period after CCE diagnosis, steroid therapy showed a good renal outcome in CCE patients. However, this treatment did not have a favorable effect on long-term renal outcome.