Sex-Specific Left Ventricular and Aorta Size Cut-Off Values for Hemodynamically Significant Chronic Aortic Regurgitation　- Implications for Treatment in Asian Populations.

BACKGROUND: There are no sex-specific guidelines for chronic aortic regurgitation (AR). This retrospective study examined sex-specific differences and propose treatment criteria from an Asian AR cohort.Methods and Results: Consecutive 1,305 patients with moderate-severe AR or greater at 3 tertiary centers in Taiwan and Japan (2008-2022) were identified. Study endpoints were aortic valve surgery (AVS), all-cause death (ACD), and cardiovascular death (CVD). The median follow up was 3.9 years (interquartile range 1.3-7.1 years). Compared with men (n=968), women (n=337) were older, had more advanced symptoms, more comorbidities, larger indexed aorta size (iAortamax) and indexed left ventricular (LV) end-systolic dimension (LVESDi; P<0.001 for all). Symptomatic status was poorly correlated with the degree of LV remodeling in women (P≥0.18). Women received fewer AVS (P≤0.001) and men had better overall 10-year survival (P<0.01). Ten-year post-AVS survival (P=0.9) and the progression of LV remodeling were similar between sexes (P≥0.16). Multivariable determinants of ACD and CVD were age, advanced symptoms, iAortamax, LV ejection fraction (LVEF), LVESDi, LV end-systolic volume index (LVESVi), and Taiwanese ethnicity (all P<0.05), but not female sex (P≥0.05). AVS was associated with better survival (P<0.01). Adjusted LVEF, LVESDi, LVESVi, and iAortamaxcut-off values for ACD were 53%, 24.8 mm/m2, 44 mL/m2, and 25.5 mm/m2, respectively, in women and 52%, 23.4 mm/m2, 52 mL/m2, and 23.2 mm/m2, respectively, in men. CONCLUSIONS: Early detection and intervention using sex-specific cut-off values may improve survival in women with AR.

Correction: Effect of Telehealth Services on Mitral and Tricuspid Regurgitation Progression: Retrospective Study.

[This corrects the article DOI: 10.2196/47947.].

Effect of Telehealth Services on Mitral and Tricuspid Regurgitation Progression: Retrospective Study.

BACKGROUND: Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common cardiac conditions with high mortality risks, which can be improved through early intervention. Telehealth services, which allow for remote monitoring of patient conditions, have been proven to improve the health management of chronic diseases, but the effects on MR and TR progression are unknown. OBJECTIVE: This study aimed to explore whether patients receiving telehealth services have less MR and TR progression compared with a control group. We also aimed to identify the determinants of MR and TR progression. METHODS: This single-center retrospective study conducted at the National Taiwan University Hospital compared MR and TR progression (defined as either progression to moderate or greater MR and TR or MR and TR progression by ≥2 grades during the study period) between the telehealth and control groups. Patients had a minimum of 2 transthoracic echocardiograms at least 6 months apart; baseline mild-moderate MR and TR or lower; and no prior surgeries on the mitral or tricuspid valve. Telehealth patients were defined as those who received telehealth services for at least 28 days within 3 months of baseline. Basic demographics, baseline blood pressure measurements, prescribed medication, and Charlson Comorbidity Index components were obtained for all patients. RESULTS: A total of 1081 patients (n=226 in the telehealth group and n=855 in the control group) were included in the study analyses. The telehealth group showed significantly lower baseline systolic blood pressure (P<.001), higher Charlson Comorbidity Index (P=.02), higher prevalence of prior myocardial infarction (P=.01) and heart failure (P<.001), higher beta-blocker (P=.03) and diuretic (P=.04) use, and lower nitrate use (P=.04). Both groups showed similar cardiac remodeling conditions at baseline. Telehealth was found to be neutral for both MR (hazard ratio 1.10, 95% CI 0.80-1.52; P=.52) and TR (hazard ratio 1.27, 95% CI 0.92-1.74; P=.14) progression. Determinants for moderate or greater MR progression included older age, female sex, diuretic use, larger left atrial dimension, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, and lower left ventricular ejection fraction. Determinants of moderate or greater TR progression included older age, female sex, diuretic use, presence of atrial fibrillation, LA dimension, left ventricular end-systolic dimension, and lower left ventricular ejection fraction; statin use was found to be protective. CONCLUSIONS: This is the first study to assess the association between telehealth services and the progression of MR and TR. Telehealth patients, who had more comorbidities, displayed similar MR and TR progression versus control patients, indicating that telehealth may slow MR and TR progression. Determinants of MR and TR progression included easy-to-measure traditional echo parameters of cardiac function, older age, female sex, and atrial fibrillation, which can be incorporated into a telehealth platform and advanced alert system, improving patient outcomes through personalized care.

Comparative Efficacy of Pharmacological Treatments for Acne Vulgaris: A Network Meta-Analysis of 221 Randomized Controlled Trials.

PURPOSE: Acne is an extremely common skin disease with an estimated global prevalence of 9.4%. We aim to provide comprehensive comparisons of the common pharmacological treatments for acne. METHODS: Randomized controlled trials comparing the efficacy of pharmacological therapies for acne vulgaris in patients of any age and sex and with a treatment duration of >2 weeks were included. PubMed and Embase databases were searched from inception until February 2022. Our prespecified primary end points were mean percentage reduction in total, inflammatory, and noninflammatory lesions. Treatment ranking was determined by P values. RESULTS: There were 210 articles describing 221 trials and 37 interventions included in the analysis. Our primary analysis of percentage reduction in total lesion count had 65,601 patients enrolled. Across all trials, the mean age was 20.4 years. The median duration of treatment was 12 weeks. The median total, inflammatory, and noninflammatory lesion counts were 72, 27, and 44, respectively. The most effective treatment was oral isotretinoin (mean difference [MD] = 48.41; P = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (BPO) (MD = 38.15; P = .95) and by triple therapy containing an oral antibiotic, a topical retinoid, and BPO (MD = 34.83; P = .90). For monotherapies, oral or topical antibiotics or topical retinoids have comparable efficacy for inflammatory lesions, while oral or topical antibiotics have less effect on noninflammatory lesions. CONCLUSION: The most effective treatment for acne is oral isotretinoin, followed by triple therapies containing a topical retinoid, BPO, and an antibiotic. We present detailed comparisons of each intervention to serve as a practical database.

Analysis of Left Ventricular Indexes and Mortality Among Asian Adults With Hemodynamically Significant Chronic Aortic Regurgitation.

Importance: Chronic hemodynamically significant aortic regurgitation (AR) is associated with excess risk of death, yet data for Asian patients are lacking, and whether Asian patients can abide by Western guidelines as to when aortic valve surgery should be performed is unknown. Objective: To assess AR presentation and cutoffs of left ventricular ejection fraction (LVEF), LV end-systolic dimension index (LVESDi), and LV end-systolic volume index (LVESVi) that are associated with risk of death in Asian patients with AR. Design, Setting, and Participants: This retrospective cohort study included consecutive patients with chronic, moderately severe to severe AR from 3 tertiary referral centers (2 in Japan and 1 in Taiwan) from June 11, 2008, through November 19, 2020, with follow-up through November 11, 2021. Exposures: Aortic regurgitation severity, graded by a comprehensive integrated approach. Main Outcomes and Measures: The primary outcome was the association between volume-derived LVEF, LVESDi, and LVESVi and all-cause death (ACD). The secondary outcome was the association of these LV indexes with cardiovascular death (CVD). Clinical and echocardiographic data were analyzed retrospectively. A de novo disk-summation method was used to derive LV volumes and volume-derived LVEF. Results: Of 1259 patients (mean [SD] age, 64 [17] years; 934 [74%] male), 515 (41%) were Japanese and 744 (59%) were Taiwanese. The median follow-up was 4.1 years (IQR, 1.56-7.24 years). The mean (SD) body surface area was 1.67 (0.21) m2; LVEF, 55% (11%); LVESDi, 24.7 (5.7) mm/m2; LVESVi, 50.1 (28.0) mL/m2; and indexed mid-ascending aorta size, 24.7 (5.5) mm/m2. Aortic valve surgery occurred in 483 patients (38%); 240 patients (19%) died during follow-up. Overall mean (SD) 8-year survival was 74% (2%). Separate multivariate models adjusted for covariates demonstrated independent associations of LVEF, LVESDi, and LVESVi with ACD (LVEF: hazard ratio [HR] per 10%, 0.80; 95% CI, 0.70-0.92; P = .002; LVESDi: HR, 1.04; 95% CI, 1.01-1.06; P = .002; LVESVi: HR per 10 mL/m2, 1.11; 95% CI, 1.05-1.17; P < .001) and CVD (LVEF: HR per 10%, 0.69; 95% CI, 0.56-0.85; P < .001; LVESDi: HR, 1.05; 95% CI, 1.01-1.09; P = .01; LVESVi per 10 mL/m2: HR, 1.15; 95% CI, 1.06-1.24; P < .001). In the total cohort, spline curves showed that mortality started to increase for an LVEF of 53% or less, LVESDi of 22 mm/m2 or greater, and LVESVi of 46 mL/m2 or greater for both ACD and CVD. Early surgery was beneficial in 3 strata of LVESDi (<20, 20 to <25, and ≥25 mm/m2) and 2 strata of LVESVi (<46 and ≥46 mL/m2). Conclusions and Relevance: This multicenter cohort study of Asian patients with hemodynamically significant AR found cutoff values of LVEF, LVESDi, and LVESVi that were associated with increased risk of death. These findings suggest that Western guidelines seem applicable in Asian patients and, most importantly, that indexed LV parameters with a lower cutoff could be used in discriminating patients with excess mortality risk.

Serum levels of copeptin predict adverse outcomes and improve risk prediction of TRISS and MGAP scores in patients with multiple trauma: A single-center prospective cohort study.

BACKGROUND: Multiple trauma deserves early prognostication and stratification. Copeptin, a precursor of vasopressin, is produced in response to stress. We examined the association between serum levels of copeptin and mortality risk in patients with multiple trauma. We aimed to also enhance the previously established Trauma-Related Injury Severity Score (TRISS) and Mechanism, GCS, Age, and Arterial Pressure (MGAP) score with the additional consideration of copeptin levels. METHODS: This single-center prospective cohort study enrolled patients who presented to the emergency department with potential major injuries. The serum levels of copeptin were measured, and the correlation to clinical severity in terms of 30-day mortality and requirement of intensive care management was analyzed. By combining copeptin levels with TRISS or MGAP, comparison between performance of the original models with the copeptin-enhanced models was performed via discrimination, calibration, and reclassification analyses. RESULTS: There was a significant increase in copeptin levels in patients who died within 30 days (median 644.4 pg/L, interquartile range [472.5, 785.9]) or were admitted to intensive care units (233.8 pg/L, [105.7, 366.4]), compared with those who survived (37.49 pg/L, [17.88, 77.68]). Adding the natural log of copeptin levels to the established TRISS and MGAP models improved the AUC of TRISS from 0.89 to 0.96, and that of MGAP from 0.82 to 0.95. Both calibrations as measured by Brier's scores and reclassification as measured by net reclassification improvement or integrated discrimination improvement demonstrated significant improvements. A Web-based calculator was built to generate predicted mortality rates of various models for convenient clinical use. CONCLUSION: Admission serum copeptin levels were correlated with clinical severity in multiple trauma. Coupling copeptin with preexisting trauma severity scores improved prediction accuracy. Copeptin shows promise as a novel biomarker for the prediction of trauma outcome. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Effect of methylprednisolone treatment on COVID-19: An inverse probability of treatment weighting analysis.

OBJECTIVES: While corticosteroids have been hypothesized to exert protective benefits in patients infected with SARS-CoV-2, data remain mixed. This study sought to investigate the outcomes of methylprednisone administration in an Italian cohort of hospitalized patients with confirmed SARS-CoV-2 infection. METHODS: Patients with confirmatory testing for SARS-CoV-2 were retrospectively enrolled from a tertiary university hospital in Milan, Italy from March 1st to April 30th, 2020 and divided into two groups by administration of corticosteroids. Methylprednisolone was administered to patients not responding to pharmacological therapy and ventilatory support at 0.5-1mg/kg/day for 4 to 7 days. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences between the steroid and non-steroid cohorts via inverse probability of treatment weight. Primary outcomes included acute respiratory failure (ARF), shock, and 30-day mortality among surviving patients. RESULTS: Among 311 patients enrolled, 71 patients received steroids and 240 did not receive steroids. The mean age was 63.1 years, 35.4% were female, and hypertension, diabetes, heart disease, and chronic pulmonary disease were present in 3.5%, 1.3%, 14.8% and 12.2% respectively. Crude analysis revealed no statistically significant reduction in the incidence of 30-day mortality (36,6% vs 21,7%; OR, 2.09; 95% CI, 1.18-3.70; p = 0.011), shock (2.8% vs 4.6%; OR, 0.60; 95% CI = 0.13-2.79; p = 0.514) or ARF (12.7% vs 15%; OR, 0.82; 95% CI = 0.38-1.80; p = 0.625) between the steroid and non-steroid groups. After IPTW analysis, the steroid-group had lower incidence of shock (0.9% vs 4.1%; OR, 0.21; 95% CI,0.06-0.77; p = 0.010), ARF (6.6% vs 16.0%; OR, 0.37; 95% CI, 0.22-0.64; p<0.001) and 30-day mortality (20.3% vs 22.8%; OR 0.86; 95% CI, 0.59-1.26 p = 0.436); even though, for the latter no statistical significance was reached. Steroid use was also associated with increased length of hospital stay both in crude and IPTW analyses. Subgroup analysis revealed that patients with cardiovascular comorbidities or chronic lung diseases were more likely to be steroid responsive. No significant survival benefit was seen after steroid treatment. CONCLUSIONS: Physicians should avoid routine methylprednisolone use in SARS-CoV-2 patients, since it does not reduce 30-day mortality. However, they must consider its use for severe patients with cardiovascular or respiratory comorbidities in order to reduce the incidence of either shock or acute respiratory failure.

Risk-standardized sepsis mortality map of the United States.

OBJECTIVE: Sepsis is the leading cause of in-hospital mortality in the United States (US). Quality improvement initiatives for improving sepsis care depend on accurate estimates of sepsis mortality. While hospital 30-day risk-standardized mortality rates have been published for patients hospitalized with acute myocardial infarction, heart failure, and pneumonia, risk-standardized mortality rates for sepsis have not been well characterized. We aimed to construct a sepsis risk-standardized mortality rate map for the United States, to illustrate disparities in sepsis care across the country. METHODS: This cross-sectional study included adults from the US Nationwide Inpatient Sample who were hospitalized with sepsis between 1 January 2010 and 30 December 2011. Hospital-level risk-standardized mortality rates were calculated using hierarchical logistic modelling, and were risk-adjusted with predicted mortality derived from (1) the Sepsis Risk Prediction Score, a logistic regression model, and (2) gradient-boosted decision trees, a supervised machine learning (ML) algorithm. RESULTS: Among 1,739,033 adults hospitalized with sepsis, 50% were female, and the median age was 71 years (interquartile range: 58-81). The national median risk-standardized mortality rate for sepsis was 18.4% (interquartile range: 17.0, 21.0) by the boosted tree model, which had better discrimination than the Sepsis Risk Prediction Score model (C-statistic 0.87 and 0.78, respectively). The highest risk-standardized mortality rates were found in Wyoming, North Dakota, and Mississippi, while the lowest were found in Arizona, Colorado, and Michigan. CONCLUSIONS: Wide variation exists in sepsis risk-standardized mortality rates across states, representing opportunities for improvement in sepsis care. This represents the first map of state-level variation of risk-standardized mortality rates in sepsis.