Sex-specific associations between sodium and potassium intake and overall and cause-specific mortality: a large prospective U.S. cohort study, systematic review, and updated meta-analysis of cohort studies.

BACKGROUND: The impact of sodium intake on cardiovascular disease (CVD) health and mortality has been studied for decades, including the well-established association with blood pressure. However, non-linear patterns, dose-response associations, and sex differences in the relationship between sodium and potassium intakes and overall and cause-specific mortality remain to be elucidated and a comprehensive examination is lacking. Our study objective was to determine whether intake of sodium and potassium and the sodium-potassium ratio are associated with overall and cause-specific mortality in men and women. METHODS: We conducted a prospective analysis of 237,036 men and 179,068 women in the National Institutes of Health-AARP Diet and Health Study. Multivariable-adjusted Cox proportional hazard regression models were utilized to calculate hazard ratios. A systematic review and meta-analysis of cohort studies was also conducted. RESULTS: During 6,009,748 person-years of follow-up, there were 77,614 deaths, 49,297 among men and 28,317 among women. Adjusting for other risk factors, we found a significant positive association between higher sodium intake (≥ 2,000 mg/d) and increased overall and CVD mortality (overall mortality, fifth versus lowest quintile, men and women HRs = 1.06 and 1.10, Pnonlinearity < 0.0001; CVD mortality, fifth versus lowest quintile, HRs = 1.07 and 1.21, Pnonlinearity = 0.0002 and 0.01). Higher potassium intake and a lower sodium-potassium ratio were associated with a reduced mortality, with women showing stronger associations (overall mortality, fifth versus lowest quintile, HRs for potassium = 0.96 and 0.82, and HRs for the sodium-potassium ratio = 1.09 and 1.23, for men and women, respectively; Pnonlinearity < 0.05 and both P for interaction ≤ 0.0006). The overall mortality associations with intake of sodium, potassium and the sodium-potassium ratio were generally similar across population risk factor subgroups with the exception that the inverse potassium-mortality association was stronger in men with lower body mass index or fruit consumption (Pinteraction < 0.0004). The updated meta-analysis of cohort studies based on 42 risk estimates, 2,085,904 participants, and 80,085 CVD events yielded very similar results (highest versus lowest sodium categories, pooled relative risk for CVD events = 1.13, 95% CI: 1.06-1.20; Pnonlinearity < 0.001). CONCLUSIONS: Our study demonstrates significant positive associations between daily sodium intake (within the range of sodium intake between 2,000 and 7,500 mg/d), the sodium-potassium ratio, and risk of CVD and overall mortality, with women having stronger sodium-potassium ratio-mortality associations than men, and with the meta-analysis providing compelling support for the CVD associations. These data may suggest decreasing sodium intake and increasing potassium intake as means to improve health and longevity, and our data pointing to a sex difference in the potassium-mortality and sodium-potassium ratio-mortality relationships provide additional evidence relevant to current dietary guidelines for the general adult population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Identifier: CRD42022331618.

Left Atrial Strain Predicts Cardiovascular and All-Cause Mortality.

Background: Left atrial strain can usefully reflect left atrial function. The follow-up periods in previous studies assessing left atrial strain as a survival predictor have been relatively short, and few studies have examined the ability of left atrial strain to predict mortality in patients with borderline diastolic function. This study sought to investigate the survival predictive value of left atrial strain with a longer follow-up duration. In addition, we also evaluated the survival predictive value of left atrial strain in patients with borderline diastolic function. Methods: In total, 652 participants who received routine echocardiography underwent 2-D speckle tracking echocardiography to evaluate left atrial reservoir function by peak atrial longitudinal strain. The study endpoints were all-cause and cardiovascular mortality. Results: The mean left atrial strain was 27.6%, and the median follow-up duration was 92 months. During follow-up, 72 patients died of cardiovascular causes and 181 died of all causes. Univariable Cox regression analysis revealed that lower left atrial strain significantly predicted an increase in all-cause and cardiovascular mortality. After adjusting for common clinical and echocardiographic parameters, lower left atrial strain was still associated with a higher risk of all-cause mortality [hazard ratio (HR) = 0.942, p = 0.011] and cardiovascular mortality (HR = 0.915, p = 0.018) in multivariable Cox-regression analysis. In addition, 293 patients had borderline left ventricular diastolic function. Multivariable analysis still revealed that left atrial strain could predict cardiovascular mortality in this population. Conclusions: Our data showed that left atrial strain could predict all-cause and cardiovascular mortality, even after adjusting for general clinical and echocardiographic parameters.

Association of physical activity with overall mortality among long-term testicular cancer survivors: A longitudinal study.

Physical activity (PA) has been associated with reduced mortality among cancer survivors, but no study has focused on testicular cancer survivors (TCSs). We aimed to investigate the association of PA measured twice during survivorship with overall mortality in TCSs. TCSs treated during 1980 to 1994 participated in a nationwide longitudinal survey between 1998 to 2002 (S1: n = 1392) and 2007 to 2009 (S2: n = 1011). PA was self-reported by asking for the average hours per week of leisure-time PA in the past year. Responses were converted into metabolic equivalent task hours/week (MET-h/wk) and participants were categorized into: Inactives (0 MET-h/wk), Low-Actives (2-6 MET-h/wk), Actives (10-18 MET-h/wk) and High-Actives (20-48 MET-h/wk). Mortality from S1 and S2, respectively, was analyzed using the Kaplan-Meier estimator and Cox proportional hazards models until the End of Study (December 31, 2020). Mean age at S1 was 45 years (SD 10.2). Nineteen percent (n = 268) of TCSs died between S1 and EoS, with 138 dying after S2. Compared to Inactives at S1, the mortality risk among Actives was 51% lower (HR 0.49, 95% CI: 0.29-0.84) with no further mortality reduction among High-Actives. At S2, the mortality risk was at least 60% lower among the Actives, High-Actives and even the Low-Actives compared to the Inactives. Persistent Actives (≥10 MET-h/wk at S1 and S2) had a 51% lower mortality risk compared to Persistent Inactives (<10 MET-h/wk at S1 and S2; HR 0.49, 95% CI: 0.30-0.82). During long-term survivorship after TC treatment, regular and maintained PA were associated with an overall mortality risk reduction of at least 50%.

A nationwide cohort study suggests clarithromycin-based therapy for Helicobacter pylori eradication is safe in patients with stable coronary heart disease and subsequent peptic ulcer disease.

BACKGROUND: Clarithromycin-based therapy is important for Helicobacter pylori eradication treatment. However, clarithromycin may increase cardiovascular risk. Hence, we investigated the association between clarithromycin use and outcomes in adults with stable coronary heart disease (CHD) and subsequent peptic ulcer disease (PUD). METHODS: This nationwide cohort study used a national health insurance database to screen 298,417 Taiwanese residents who were diagnosed with coronary heart disease from 2001 to 2015 for eligibility in the study and to evaluate select eligible patients with CHD-PUD from 2004 to 2015. Data were obtained from new users of clarithromycin (n = 4183) and nonusers of clarithromycin (n = 24,752) during follow-up. A total of 4070 eligible clarithromycin users and 4070 nonusers were subject to final analysis by 1:1 propensity score matching. Participants were followed up after receiving clarithromycin or at the corresponding date until the occurrence of cardiovascular morbidity in the presence of competing mortality, overall mortality and cardiovascular mortality, or through the end of 2015. The incidence rates and risks of overall mortality and cardiovascular outcomes were evaluated. The associations between clarithromycin and arrhythmia risk, as well as its dose and duration and overall mortality and cardiovascular outcomes were also addressed. RESULTS: Clarithromycin users were associated with adjusted hazard ratios of 1.08 (95% confidence interval, 0.93-1.24; 21.5 compared with 21.2 per 1000 patient-years) for overall mortality, 0.95 (0.57-1.59; 1.5 compared with 1.8 per 1000 patient-years) for cardiovascular mortality, and 0.94 (0.89-1.09; 19.6 compared with 20.2 per 1000 patient-years) for cardiovascular morbidity in the presence of competing mortality, as compared with nonusers. We found no relationship between dose and duration of clarithromycin and overall mortality and cardiovascular outcomes and no increased risk of arrhythmia during follow-up period. After inclusion of arrhythmia events to re-estimate the risks of all study outcomes, the results remained insignificant. CONCLUSION: Concerning overall mortality, cardiovascular mortality, and cardiovascular morbidity, our results suggest clarithromycin-based therapy for Helicobacter pylori eradication may be safe in patients with stable CHD and subsequent PUD.

Relationship between chocolate consumption and overall and cause-specific mortality, systematic review and updated meta-analysis.

Chocolate is a rich dietary source of various bioactive flavonoid compounds. Despite being one of the most popular foods worldwide, the association between chocolate consumption and long-term mortality remains unclear. The objective of this study is to determine the associations between chocolate consumption and long-term overall and cause-specific mortality, to evaluate dose-response and potential mediators, and to conduct an updated meta-analysis based on prospective cohort studies. We performed a prospective analysis in the Alpha-Tocopherol, Beta-Carotene cancer prevention (ATBC) Study with a total of 27,111 men who were recruited between 1985 and 1988 and followed through 2015. Exposure data of daily chocolate consumption was obtained from validated baseline food frequency questionnaire. Hazard ratios (HRs) and 30-year absolute risk differences (ARDs) including 95% confidence intervals (CI) for overall and cause-specific mortality were estimated using multivariable-adjusted Cox proportional hazards regression models. An updated meta-analysis of cohort studies was also conducted. During 482,807 person-years of follow-up, a total of 22,064 men died. The multivariable analyses showed a statistically significant inverse association between chocolate consumption and risk of overall mortality, with HRs of 0.91, 0.89, 0.89, and 0.88 for the increasing categories 2-5 as compared with those in the lowest category (Ptrend < 0.0001, and P for nonlinearity < 0.0001). We observed significantly lower mortality from cardiovascular disease (CVD), heart disease and cancer, representing 13%, 16% and 12% risk reductions for the highest compared to lowest chocolate category, respectively (all Ptrend ≤ 0.002; all P for nonlinearity < 0.0001). The inverse associations of chocolate consumption with risk of overall, CVD and heart disease mortality were generally consistent across cohort subgroups (e.g., body mass index and serum cholesterol). Mediation analysis showed that 4.3% of the inverse association of chocolate and overall mortality was mediated through reducing blood pressure. Within the updated meta-analysis of cohort studies (21 risk estimates, 908,390 participants and 65,407 events), greater consumption of chocolate (per 5 g/day) was associated with a lower risk of CVD incidence and mortality (pooled relative risk = 0.98, P value < 0.001; P for nonlinearity < 0.001). The predefined subgroup analyses generally revealed consistent inverse chocolate-CVD risk associations. In this prospective study, calorie-balanced greater consumption of chocolate was inversely associated with lower overall, CVD, heart disease and cancer mortality. The systematic review and meta-analysis provide support for the inverse chocolate-CVD association. Our findings may provide evidence to partially allay concerns regarding adverse health outcomes from low-to-moderate chocolate consumption.

Bullous Pemphigoid-Associated Mortality Rate in a Canadian Tertiary Referral Centre.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disorder in adults. Most individuals with BP are over the age of 60. Its worldwide incidence has been increasing owing to population aging. Observational studies published over the last 2 decades highlight the non-negligible, albeit variable overall mortality of BP patients, with reported 12-month mortality rates of 10.8% to 40.8%, and 24-month mortality rates of 20.1% to 51.0%. Data in the Canadian population are lacking. OBJECTIVES: We aimed to estimate the 12- and 24-month overall mortality rate of Canadian patients diagnosed with BP, and to identify independent risk factors adversely impacting overall survival. METHODS: A retrospective cohort study of 166 patients with a diagnosis of BP between 2010 and 2020 was carried out at Centre hospitalier de l'Université de Montréal (CHUM), a tertiary referral center in Montréal, Québec, Canada. Cumulative mortality was calculated using the Kaplan-Meier estimator, and independent prognostic factors were identified using a Cox proportional hazards regression model. RESULTS: Eighty-five patients (51.2%) in our study were female. The median age was 79.1 years old, and 80 patients (48.2%) were 80 years old or older. Mortality at 12 and 24 months in our study cohort was 16.2% (CI95% = 10.5 - 21.8) and 27.6% (CI95% = 20.5 - 34.7), respectively. In a multivariate analysis, patients who were male, 80 years old or older, and/or had a diagnosis of a major neurocognitive disorder had a poorer overall survival. CONCLUSIONS: The all-cause mortality of patients with BP in our study population compared favorably with international data reported in the literature.

Analysis of radiotherapy impact on survival in resected stage I/II pancreatic cancer patients: a population-based study.

BACKGROUND: The application of radiotherapy (RT) in pancreatic cancer remains controversial. AIM: The aim of the study was to evaluate the efficacy of radiotherapy (neoadjuvant and adjuvant radiotherapy) for resectable I/II pancreatic cancer. METHODS: Fourteen thousand nine hundred seventy-seven patients with pancreatic cancer were identified from SEER database from 2004 to 2015. Multivariate analyses were performed to determine factors including RT on overall survival. Overall survival and overall mortality among the different groups were evaluated using the Kaplan-Meier method and Gray's test. RESULTS: Patients were divided into groups according to whether they received radiotherapy or not. The median survival time of all 14,977 patients without RT was 20 months, neoadjuvant RT was 24 months and adjuvant RT was 23 months (p < 0.0001). Median survival time of 2089 stage I patients without RT was 56 months, significantly longer than those with RT regardless of neoadjuvant or adjuvant RT (no RT: 56 months vs adjuvant RT: 37 months vs neoadjuvant RT: 27 months, P = 0.0039). Median survival time of 12,888 stage II patients with neoadjuvant RT was 24 months, adjuvant RT 22 months, significantly prolonged than those without radiotherapy (neoadjuvant RT: 24 months vs adjuvant RT: 22 months vs no RT: 17 months, P<0.0001). Neoadjuvant RT (HR = 1.434, P = 0.023, 95% CI: 1.051-1.957) was independent risk factors for prognosis of stage I patients, and adjuvant RT (HR = 0.904, P < 0.001, 95% CI: 0.861-0.950) predicted better outcomes for prognosis of stage II patients by multivariate analysis. The risk of cancer-related death caused by neoadjuvant RT in stage I and no-RT in stage II patients were significantly higher. CONCLUSIONS: The study identified a significant survival advantage for the use of adjuvant RT over surgery alone or neoadjuvant RT in treating stage II pancreatic cancer. RT was not associated with survival benifit in stage I patients.

Risk factors and outcomes of post-transplant erythrocytosis among adult kidney transplant recipients: a systematic review and meta-analysis.

Post-transplant erythrocytosis (PTE) can occur in up to 10-16% after kidney transplant (KT). However, the post-transplant outcomes of recipients with PTE in the literature were conflicting. We performed systematic review and meta-analysis of published studies to evaluate risk factors of PTE as well as outcomes of recipients who developed PTE compared with controls. A literature search was conducted evaluating all literature from existence through February 2, 2021, using MEDLINE and EMBASE. Data from each study were combined using the random-effects model. (PROSPERO: CRD42021230377). Thirty-nine studies from July 1982 to January 2021 were included (7,099 KT recipients). The following factors were associated with PTE development: male gender (pooled RR = 1.62 [1.38, 1.91], I2 = 39%), deceased-donor KT (pooled RR = 1.18 [1.03, 1.35], I2 = 32%), history of smoking (pooled RR = 1.36 [1.11, 1.67], I2 = 13%), underlying polycystic kidney disease (PKD) (pooled RR=1.56 [1.21, 2.01], I2 =44%), and pretransplant dialysis (pooled RR=1.6 [1.02, 2.51], I2 =46%). However, PTE was not associated with outcomes of interest, including overall mortality, death-censored graft failure, and thromboembolism. Our meta-analysis demonstrates that male gender, deceased-donor KT, history of smoking, underlying PKD, and pretransplant dialysis were significantly associated with developing PTE. However, with proper management, PTE has no impact on prognosis of KT patients.

Usefulness of Ankle-Brachial Index Calculated Using Diastolic Blood Pressure and Mean Arterial Pressure in Predicting Overall and Cardiovascular Mortality in Hemodialysis Patients.

No study has investigated the predictive ability of ankle-brachial index (ABI) calculated using diastolic blood pressure (DBP) (ABIdbp) and mean arterial pressure (MAP) (ABImap) for overall and cardiovascular (CV) mortality in hemodialysis (HD) patients. Our study was aimed to investigate the issue. Two hundred and seven routine HD patients were enrolled. ABI values were measured by ABI-form device. During the follow-up period (122 months), 124 of the 207 patients (59.0%) died, and 59 deaths due to CV cause. Multivariate analysis showed that low ABIsbp, ABIdbp, and ABImap were all significantly associated with increased overall (p ≤ 0.015) and CV mortality (p ≤ 0.015) in whole study patients. A subgroup analysis after excluding 37 patients with ABIsbp < 0.9 or > 1.3 found ABIsbp and ABIsbp < 0.9 were not associated with overall and CV mortality. However, ABImap and ABIdbp < 0.87 were significantly associated with overall mortality (p ≤ 0.042). Furthermore, ABIdbp and ABIdbp < 0.87 were significantly associated with CV mortality (p ≤ 0.030). In conclusion, ABIsbp, ABIdbp, and ABImap were all useful in predicting overall and CV mortality in our HD patients. In the subgroup patients with normal ABIsbp, ABIsbp and ABIsbp < 0.9 were not useful to predict overall and CV mortality. Nevertheless, ABImap and ABIdbp < 0.87 could still predict overall mortality, and ABIdbp and ABIdbp < 0.87 could predict CV mortality. Hence, calculating ABI using DBP and MAP may provide benefit in survival prediction in HD patients, especially in the patients with normal ABIsbp.

Comparison of survival outcomes between primary and secondary muscle-invasive bladder cancer: An updated meta-analysis.

Objective: Studies have showed that different follow-up starting points might potentially impact the comparison between primary (PMIBC) and secondary muscle-invasive bladder cancer (SMIBC), but the only previous meta-analysis did not differentiate the follow-up starting points of included studies. With more trials published, we aim to update the meta-analysis comparing PMIBC and SMIBC. Methods: PubMed, Embase, Cochrane Library and ClinicalTrial.gov. systematically searched. Literatures comparing the survival outcomes of PMIBC and SMIBC were selected. Outcomes of cancer-specific mortality (CSM), overall mortality (OM) and recurrence-free survival (RFS) were pooled and grouped based on the starting point of follow-up (after initial diagnosis or radical cystectomy (RC)). Newcastle-Ottawa Scale (NOS) and funnel plot were employed to assess the study quality and publication bias, respectively. Results: A total of 17 high-quality studies were selected, with 5558 patients aged from 59.8 to 72.7 (mean value) involved. The male-to-female ratio was roughly 4:1 (4390/1124). SMIBC had lower risk of CSM after initial diagnosis (HR 0.81, 95%CI 0.67-0.98, P=0.03, I2=70%), but higher risk of CSM after RC (HR 1.45, 95%CI 1.27-1.65, P<0.00001, I2=64%). In terms of OM and recurrence, outcomes were pooled only after RC, which both turned out to be higher for SMIBC (OM: HR 1.50, 95%CI 1.30-1.73, P<0.00001, I2=0%; Recurrence: HR 1.66, 95%CI 1.36-2.02, P<0.00001, I2=48%). No obvious publication bias was observed from funnel plot. Conclusion: The current study suggested SMIBC had higher risk of CSM, OM and recurrence after RC, but lower risk of CSM after initial diagnosis.

Obesity and overall mortality: findings from the Jackson Heart Study.

BACKGROUND: Overall mortality has been reported to be lower among individuals classified as overweight/obese when compared with their normal weight counterparts ("obesity paradox") when obesity classification is based on the body mass index (BMI). One possible reason for this apparent paradox is that BMI is not a reliable measure of obesity-related risk as it does not differentiate fat mass from lean muscle mass or fat mass phenotypes. Waist circumference (WC), as a measure of central adiposity, may be a better indicator of obesity-related risk. We examined the association of overall mortality with BMI and with WC measures, including WC, waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR). METHODS: Data from 3976 African American participants (551 deaths) in the Jackson Heart Study (JHS) were analyzed. Cox regression models were used to perform survival analysis. Obesity measures were analyzed as dichotomous (obese/non-obese) and continuous variables. Baseline covariates included age, sex and smoking status. RESULTS: Comparing obese to non-obese participants, adjusted hazard ratios (95% CI) for overall mortality were 1.14 (0.96, 1.35), 1.30 (1.07, 1.59), 1.02 (0.73, 1.41) and 1.45 (1.18, 1.79) when using BMI, WC, WHtR and WHR, respectively. For BMI, WC and WHtR, a J-shaped relationship was observed with overall mortality. For WHR, a monotonic increasing relationship was observed with overall mortality. CONCLUSIONS: In the JHS, we found that obesity as defined by WC and WHR was associated with an increased risk of overall and CVD mortality, while obesity defined by BMI was associated only with an increased risk of CVD mortality. WHR was the only obesity measure that showed a monotonic increasing relationship with overall and CVD mortality.

Five-year outcomes of rapid-deployment aortic valve replacement with the Edwards Intuity valve.

BACKGROUND: This report presents 5-year outcomes of the rapid-deployment Edwards Intuity valve in a prospective, single-center study. METHODS: All patients who underwent an aortic valve replacement (AVR) with an Edwards Intuity bioprosthesis at La Timone Hospital, Marseille, France, from July 2012 to June 2015 were assessed over a 5-year follow-up period. The primary outcome was overall mortality at 5 years. Secondary outcomes were reoperation, overall mortality and stroke, cardiovascular mortality, composite endpoints defined by the updated Valve Academic Research Consortium-2 (VARC-2), periprosthetic regurgitation, prosthesis-patient mismatch, and the need for new pacemaker implantation. RESULTS: In total, 170 consecutive patients were assessed, of which 67.1% were males. The mean age was 76 years, mean EuroSCORE II was 3.5% and 5-year overall mortality was 12.4%. At 5 years, reoperation was 2.9%, overall mortality and stroke was 4.1% per patient-year, and cardiovascular mortality was 4.7%. VARC clinical efficacy and VARC time-related valve safety were achieved in 46.0% and 59.9% of patients, respectively. At one month VARC device success was 71.2% and VARC early safety was 87.1%. At one year, mild and moderate periprosthetic regurgitation were 2.4% and 0.6%, respectively, and moderate and severe prosthesis-patient mismatch were 18.8% and 4.8%, respectively. Conduction disturbances needing new PPI occurred in 3.5% patients. CONCLUSION: The 5-year outcomes of AVR with the Edwards Intuity valve system demonstrate satisfactory midterm safety and excellent haemodynamic performance.

Peritoneal transport status and first episode of peritonitis: a large cohort study.

BACKGROUND: Peritonitis is one of the most serious complications of peritoneal dialysis (PD). This study aimed to explore the relationship between peritoneal transport status and the first episode of peritonitis, as well as the prognosis of patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHOD: A retrospective cohort study was conducted, analyzing data of CAPD patients from 1st January 2009, to 31st December 2017. Baseline data within 3 months after PD catheter placement was recorded. Cox multivariate regression analysis was performed to determine the risk factors for the first episode of peritonitis, technique failure and overall mortality. RESULTS: A total of 591 patients were included in our analysis, with a mean follow-up visit of 49 months (range: 27-75months). There were 174 (29.4%) patients who had experienced at least one episode of peritonitis. Multivariate Cox regression analysis revealed that a higher peritoneal transport status (high and high-average) (HR 1.872, 95%CI 1.349-2.599, p = 0.006) and hypoalbuminemia (HR 0.932,95% CI 0.896, 0.969, p = 0.004) were independent risk factors for the occurrence of the first episode of peritonitis. In addition, factors including gender (male) (HR 1.409, 95%CI 1.103, 1.800, p = 0.010), low serum albumin (HR 0.965, 95%CI 0.938, 0.993, p = 0.015) and the place of residence (rural) (HR 1.324, 95%CI 1.037, 1.691, p = 0.024) were independent predictors of technique failure. Furthermore, low serum albumin levels (HR 0.938, 95%CI 0.895, 0.984, p = 0.008) and age (>65years) (HR 1.059, 95%CI 1.042, 1.076, p < 0.001) were significantly associated with the risk of overall mortality of PD patients. CONCLUSIONS: Baseline hypoalbuminemia and a higher peritoneal transport status are risk factors for the first episode of peritonitis. Factors including male gender, hypoalbuminemia, and residing in rural areas are associated with technique failure, while hypoalbuminemia and age (>65years) are predictors of the overall mortality in PD patients. Nevertheless, the peritoneal transport status does not predict technique failure or overall mortality of PD patients.

Comparative performance and external validation of the multivariable PREDICT Prostate tool for non-metastatic prostate cancer: a study in 69,206 men from Prostate Cancer data Base Sweden (PCBaSe).

BACKGROUND: PREDICT Prostate is an endorsed prognostic model that provides individualised long-term prostate cancer-specific and overall survival estimates. The model, derived from UK data, estimates potential treatment benefit on overall survival. In this study, we externally validated the model in a large independent dataset and compared performance to existing models and within treatment groups. METHODS: Men with non-metastatic prostate cancer and prostate-specific antigen (PSA) < 100 ng/ml diagnosed between 2000 and 2010 in the nationwide population-based Prostate Cancer data Base Sweden (PCBaSe) were included. Data on age, PSA, clinical stage, grade group, biopsy involvement, primary treatment and comorbidity were retrieved. Sixty-nine thousand two hundred six men were included with 13.9 years of median follow-up. Fifteen-year survival estimates were calculated using PREDICT Prostate for prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). Discrimination was assessed using Harrell's concordance (c)-index in R. Calibration was evaluated using cumulative available follow-up in Stata (TX, USA). RESULTS: Overall discrimination of PREDICT Prostate was good with c-indices of 0.85 (95% CI 0.85-0.86) for PCSM and 0.79 (95% CI 0.79-0.80) for ACM. Overall calibration of the model was excellent with 25,925 deaths predicted and 25,849 deaths observed. Within the conservative management and radical treatment groups, c-indices for 15-year PCSM were 0.81 and 0.78, respectively. Calibration also remained good within treatment groups. The discrimination of PREDICT Prostate significantly outperformed the EAU, NCCN and CAPRA scores for both PCSM and ACM within this cohort overall. A key limitation is the use of retrospective cohort data. CONCLUSIONS: This large external validation demonstrates that PREDICT Prostate is a robust and generalisable model to aid clinical decision-making.

Incidence, features, and outcomes of cytomegalovirus DNAemia in unmanipulated haploidentical allogeneic hematopoietic stem cell transplantation with post-transplantation cyclophosphamide.

BACKGROUND: Conflicting data have been published as to the risk of cytomegalovirus (CMV) DNAemia and CMV disease in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide. METHODS: We conducted a multicenter retrospective study including 118 patients subjected to unmanipulated haplo-HSCT to further clarify this issue. An historic cohort comprising 165 patients undergoing other transplant modalities (HLA-matched related, matched unrelated or mismatched) was built for comparison purposes. Plasma CMV DNA monitoring was performed using two highly sensitive real-time PCR assays. RESULTS: Overall, the cumulative incidence of CMV DNAemia, recurrent CMV DNAemia, and CMV DNAemia requiring preemptive antiviral therapy in patients undergoing haplo-HSCT was 63.9%, 34.9%, and 50.1%, respectively. These figures were rather comparable for other transplant modalities (P = .22, P = .13 and P = .72, respectively). A trend toward longer duration of episodes and shorter CMV DNA doubling times was observed in haplo-HSCT patients in comparison with other transplant modalities. Furthermore, median CMV DNA peak load was significantly higher in haplo-HSCTs (P = .008), yet overall mortality by day 180 and 365 was the same across comparison groups. There were five cases of CMV disease, and all occurred in haplo-HSCT patients. This latter observation is worrying and merits further investigation. CONCLUSIONS: The incidence of initial and recurrent episodes of CMV DNAemia either requiring or not antiviral therapy in unmanipulated haplo-HSCT was comparable to other transplant modalities in our cohort.

Increased Proteinuria is Associated with Increased Aortic Arch Calcification, Cardio-Thoracic Ratio, Rapid Renal Progression and Increased Overall and Cardiovascular Mortality in Chronic Kidney Disease.

Background: Patients with chronic kidney disease (CKD) are associated with high prevalence rates of proteinuria, vascular calcification and cardiomegaly. In this study, we investigated relationships among proteinuria, aortic arch calcification (AoAC) and cardio-thoracic ratio (CTR) in patients with CKD stage 3A-5. In addition, we investigated correlations among proteinuria and decline in renal function, overall and cardiovascular (CV) mortality. Methods: We enrolled 482 pre-dialysis patients with CKD stage 3A-5, and determined AoAC and CTR using chest radiography at enrollment. The patients were stratified into four groups according to quartiles of urine protein-to-creatinine ratio (UPCR). Results: The patients in quartile 4 had a lower estimated glomerular filtration rate (eGFR) slope, and higher prevalence rates of rapid renal progression, progression to commencement of dialysis, overall and CV mortality. Multivariable analysis showed that a high UPCR was associated with high AoAC (unstandardized coefficient ß: 0.315; p = 0.002), high CTR (unstandardized coefficient ß: 1.186; p = 0.028) and larger negative eGFR slope (unstandardized coefficient ß: -2.398; p < 0.001). With regards to clinical outcomes, a high UPCR was significantly correlated with progression to dialysis (log per 1 mg/g; hazard ratio [HR], 2.538; p = 0.003), increased overall mortality (log per 1 mg/g; HR, 2.292; p = 0.003) and increased CV mortality (log per 1 mg/g; HR, 3.195; p = 0.006). Conclusions: Assessing proteinuria may allow for the early identification of high-risk patients and initiate interventions to prevent vascular calcification, cardiomegaly, and poor clinical outcomes.

The impact of menopausal hormone therapy on overall mortality - a comprehensive review.

Menopausal hormone therapy (MHT) is indicated for menopausal symptom relief. However, MHT has also been shown to be beneficial for prevention of long-term estrogen deficiency sequelae including mortality. Based on a comprehensive literature review on MHT and mortality, the authors' recommendations are as follows: in postmenopausal women, MHT appears to confer a (significant) reduction in overall mortality; the benefit especially applies to women who initiate long-term MHT early after menopause; in women with prevalent cardiovascular risk factors (except for diabetes mellitus, where results are mixed), the benefit of MHT on overall mortality is even more pronounced; and, however, study results are difficult to compare due to heterogeneous study designs.

Classification of weekly provincial overall age- and gender-specific mortality patterns during the COVID-19 epidemics in Italy.

OBJECTIVES: to provide a time-varying classification of the Italian provinces based on the weekly age- and gender-specific relative risks (RR) for overall mortality, obtained comparing the number of deaths from 13 weeks from the beginning of the COVID-19 epidemics, with the average number of deaths from the same period in 2015-19. DESIGN: population overall mortality data provided by the Italian National Statistical Office (Istat). SETTING AND PARTICIPANTS: Italian residents 60 years or older from 7,357/7,904 Italian municipalities. For the included municipalities, the number of deaths from any cause from 1 January to 30 May 2020 was available for each day of the 2015-2020 period. Data were stratified by gender, 4 age categories (60-69, 70-79, 80-89, 90+), week, and province. MAIN OUTCOME MEASURES: province- and gender-specific weekly RR curves (age category vs RR), obtained for 13 weeks between 26 February and 26 May; excess mortality; time-varying/weekly classification of provinces. RESULTS: these results provide a weekly classification of the Italian provinces based on their RR curves in 5 groups, 2 of which had high and very high excess mortality during the epidemics. Most of the provinces that appeared at least once in the highest-risk group are neighbouring provinces in the Northern Regions of Lombardy, Emilia-Romagna, Piedmont, and Marche (in central Italy), where most of the COVID-19 cases and deaths were identified. Temporally, most of these provinces remained in the highest-risk group for 4 or 5 weeks; those that entered the group later, improved faster. The overall RR curves for groups differed in magnitude, but also in the shape, which varied markedly also between men and women and, most importantly, in the highest-risk group. CONCLUSIONS: this study gives timely re-analysis of the Istat data at weekly level and provides a classification of the geographical and temporal characteristics of the excess mortality in the Italian provinces during the COVID-19 epidemics. As expected, the used clustering method groups the provinces that have similar RR values in the two gender-specific curves. The results facilitate the presentation of the spatio-temporal mortality patterns of the epidemics and provide evidence of high heterogeneity in the group of provinces that were defined as high-risk groups by others, based on their geographical position or on the time of the observed spread of the virus.

Identifying the Italian provinces with increased mortality during COVID-19 epidemics using the data made available by the Italian National Institute of Statistics. A methodological challenge.

OBJECTIVES: to identify the Italian provinces with excess mortality during the COVID-19 epidemics using the mortality data provided in April 2020 by the Italian National Institute of Statistics (Istat) that, by design, included only the municipalities with at least 20% mortality increase compared to the same period in 2015-19. Inference with the aim to identify increased mortality at provincial level was a very important task when the Istat data were released in April, but the naïve aggregation of the selected municipalities was not sensible to due to the selection criteria of the municipalities used by Istat. DESIGN: use of a permutation-based approach to identify the Italian provinces with excess mortality during the first month of the COVID-19 epidemics using the data made available from Istat and taking into account the biased inclusion criteria. SETTING AND PARTICIPANTS: the number of deaths from any cause from 1 January was available for each year of the 2015-2020 period. Data were stratified by municipality, sex and 21 age categories. The third data release (R3) included 1,686 of the 7,904 Italian municipalities with increased mortality in 2020, covering about 40% of the Italian population. Results were compared with those obtainable with the fifth data release (R5), made available in June, when the selection of the municipalities was no longer based on increased mortality and which included more than 90% of the Italian population. R5 was considered the gold standard. MAIN OUTCOME MEASURES: excess of deaths from any cause in the Italian provinces between 1 March and 4 April; relative risk (RR); permutation p-values; permutation-based adjusted relative risk; population coverage. RESULTS: the results of this study, which are based on two different test statistics, identify 17 and 33 provinces (out of 103) with increased overall mortality, respectively, controlling the family-wise error rate at 0.05 level. Most of the identified provinces are neighbouring provinces in the northern regions of Lombardy, Emilia-Romagna, Piedmont, Liguria, Marche and Tuscany, where most of the COVID-19 cases and deaths were identified. The comparison with data from R5 shows that all the identified provinces had an increase in overall mortality, mostly (31/34) above 25%. On average, the adjusted RR slightly underestimates the RR from R5, underestimating the large RR and overestimating the small RR. CONCLUSIONS: this was, to the best of the authors' knowledge, the first attempt to aggregate the Istat data at province level and obtain a reliable and generalizable statistical inference. This permutation-based approach provides a feasible approach to take into account the selection bias that was present in the data and could be used for analysing other types of data that present some type of selection bias.

Spontaneously-resolving episodes of cytomegalovirus DNAemia in allogeneic hematopoietic stem cell transplant recipients: Virological features and clinical outcomes.

It has been reported that low-plasma cytomegalovirus (CMV) DNA loads are associated with an increased risk of overall mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Utilizing a conservative strategy for initiation of preemptive antiviral therapy (>1500 IU/mL), we characterized the virological features of spontaneously-resolving episodes of CMV DNAemia and assessed their impact on mortality through the first year after transplantation. We reviewed the CMV DNA polymerase chain reaction results and clinical charts of 230 consecutive adult patients who underwent T-cell replete allo-HSCT at our center. A total of 280 episodes of CMV DNAemia were registered in 164 patients, of which 144 episodes cleared spontaneously. Clearance of CMV DNAemia was significantly delayed in initial and recurrent self-resolving episodes featuring CMV DNA peak loads > 250 IU/mL compared with those displaying lower values. All-cause mortality in patients with self-resolving episodes of CMV DNAemia was comparable (P = 0.7) to that in patients with no CMV DNAemia and was not related to the CMV DNA peak load (≥250 IU/mL vs <250 IU/mL) (P = 0.6). In summary, in our setting, the magnitude of the CMV DNA peak load reached during self-resolving episodes of CMV DNAemia correlated directly with duration of episodes, but had no apparent impact on all-cause mortality taking patients with no documented CMV DNAemia as a reference.