Multiplicity 1: Subgroup analyses

Limb girdle muscular dystrophy (LGMD) 2A/R1, caused by mutations in the CAPN3 gene and CAPN3 loss of function, is known to play a role in disease pathogenicity. In this study, AAVrh74.tMCK.CAPN3 was delivered systemically to two different age groups of CAPN3 knockout (KO) mice; each group included two treatment cohorts receiving low (1.17 × 1014 vg/kg) and high (2.35 × 1014 vg/kg) doses of the vector and untreated controls. Treatment efficacy was tested 20 weeks after gene delivery using functional (treadmill), physiological (in vivo muscle contractility assay), and histopathological outcomes. AAV.CAPN3 gene therapy resulted in significant, robust improvements in functional outcomes and muscle physiology at low and high doses in both age groups. Histological analyses of skeletal muscle showed remodeling of muscle, a switch to fatigue-resistant oxidative fibers in females, and fiber size increases in both sexes. Safety studies revealed no organ tissue abnormalities; specifically, there was no histopathological evidence of cardiotoxicity. These results show that CAPN3 gene replacement therapy improved the phenotype in the CAPN3 KO mouse model at both doses independent of age at the time of vector administration. The improvements were supported by an absence of cardiotoxicity, showing the efficacy and safety of the AAV.CAPN3 vector as a potential gene therapy for LGMDR1.

Focus

Objective Hysterectomy rates have fallen over recent years and there remains debate whether salpingectomy should be performed to reduce the lifetime risk of ovarian cancer. We examined trends in adnexal removal and route of hysterectomy in Australia between 2001 and 2015. Methods Data were obtained from the national procedural dataset for hysterectomy approach (vaginal, VH; abdominal, AH; and, laparoscopic, LH) and rates of adnexal removal, as well as endometrial ablation. The total female population in two age groups (“younger age group,” 35 to 54 years, and “older age group,” 55 to 74 years) was obtained from the Australian Bureau of Statistics. Results The rate of hysterectomy fell in both younger (61.7 versus 45.2/10000/year, p < 0.005) and older (38.8 versus 33.2/10000/year, p < 0.005) age groups. In both age groups there were significant decreases in the incidence rates for VH (by 53% in the younger age group and 29% in the older age group) and AH (by 53% and 55%, respectively). The rates of LH increased by 153% in the younger age group and 307% in the older age group. Overall, the proportion of hysterectomies involving adnexal removal increased (31% versus 65% in the younger age group, p < 0.005; 44% versus 58% in the older age group, p < 0.005). The increase occurred almost entirely after 2011. Conclusion Hysterectomy is becoming less common, and both vaginal and abdominal hysterectomy are being replaced by laparoscopic hysterectomy. Removal of the adnexae is now more common in younger women.

Sex Differences in Early Carotid Atherosclerosis (from the Community-Based Gutenberg-Heart Study)

We aimed to elucidate the factors for the decision-making process in the treatment of adult spinal deformity (ASD), including sagittal parameters, that impact health-related quality of life (HRQOL). A multicenter prospective ASD database was retrospectively reviewed. The demographic data, HRQOL, and radiographic measures were analyzed using multivariate analyses in younger (≤ 50years) and older (> 50years) age groups. This study included 414 patients (134 surgical and 280 nonsurgical; mean age 30.7years) in the younger age group and 575 patients (323 surgical and 252 nonsurgical; mean age 65.8years) in the older age group. Worse HRQOL measures drove surgical treatment, both in younger and older patients. The SRS-22 self-image score was the most differentiating domain, both in the younger and older age groups, and an additional significant factor in the older age group was pain and disability. Coronal deformity drove surgical treatment for the younger age group; however, older surgical patients were less likely to have coronal malalignment. Sagittal parameters were associated with the decision-making process. Greater pelvic incidence minus lumbar lordosis mismatch in the younger age group and smaller lumbar lordosis index in the older age group were most correlated with the decision to undergo surgery. Aside from the HRQOL measures and coronal deformity, sagittal parameters were identified as significant factors for the decision-making process in the ASD population, and the lack of lumbar lordosis in relation to pelvic incidence was a strong driver to pursue surgical treatment. These slides can be retrieved under Electronic Supplementary Material.

Purpose We investigated associations of blood pressure (BP) with albuminuria and left ventricular hypertrophy (LVH) in young, middle and older aged patients with hypertension and/or diabetes mellitus. Materials & Methods Study participants were treated patients with hypertension or diabetes, enrolled in a China nationwide registry. The 2510 patients were classified into young (<45 years, n = 345), middle (45–64 years, n = 1383) and older (≥65 years, n = 782) age groups. Clinic BP was measured three times consecutively on each of the two clinic visits. These six readings were averaged for analyses. Albuminuria was defined as a urinary albumin-to-creatinine ratio of ≥30 mg/g. LVH was assessed by the electrocardiogram (ECG) Cornell product and voltage methods. Results The prevalence of albuminuria and ECG-LVH was 17.8 and 6.5%, respectively. Mean (±SD) systolic/diastolic BP was 132.0 ± 16.5/85.2 ± 11.9 mmHg, 136.8 ± 17.9/81.7 ± 11.2 mmHg, and 139.8 ± 16.7/75.8 ± 10.4 mmHg in the young, middle and older age groups. In the young age group, the prevalence of albuminuria increased from 8.8% in systolic/diastolic BP <120/80 mmHg to 14.6, 16.0% and 16.5% in 120–129/80–84, 130–139/85–89 and ≥140/90 mmHg, respectively. The corresponding values were 8.9, 7.0, 18.1 and 22.2%, respectively, in the middle age group, and 21.2, 15.5, 16.4 and 24.4%, respectively, in the older age group. Adjusted analyses confirmed the J-shaped relation between BP and albuminuria in the older but not young age group. The prevalence of ECG-LVH was significantly (p for trend ≤0.04) higher with increasing BP similarly in all age groups. Conclusions The association between BP and organ damage seems to differ in young, middle and older aged patients for albuminuria but not ECG-LVH.

Prevalence of somatoform disorders and medically unexplained symptoms in old age populations in comparison with younger age groups: A systematic review

We report the bone attenuation of ankle joint measured on computed tomography (CT) and the cause of injury in patients with ankle fractures. The results showed age- and gender-dependent low bone attenuation and low-energy trauma in elderly females, which suggest the osteoporotic features of ankle fractures. This study was performed to investigate the osteoporotic features of ankle fracture in terms of bone attenuation and cause of injury. One hundred ninety-four patients (mean age 51.0 years, standard deviation 15.8 years; 98 males and 96 females) with ankle fracture were included. All patients underwent CT examination, and causes of injury (high/low-energy trauma) were recorded. Mean bone attenuations of the talus, medial malleolus, lateral malleolus, and distal tibial metaphysis were measured on CT images. Patients were divided into younger age (<50 years) and older age (≥50 years) groups, and mean bone attenuation and causes of injury were compared between the two groups in each gender. Proportion of low-energy trauma was higher in the older age group than in the younger age group, but the difference was only significant in female gender (p = 0.011). The older age group showed significantly lower bone attenuation in the talus, medial malleolus, lateral malleolus, and distal tibial metaphysis than the younger age group in both genders. The older age group showed more complex pattern of fractures than the younger age group. With increasing age, bone attenuations tended to decrease and the difference of bone attenuation between the genders tended to increase in the talus, medial malleolus, lateral malleolus, and distal tibial metaphysis. Ankle fracture had features of osteoporotic fracture that is characterized by age- and gender-dependent low bone attenuation. Ankle fracture should not be excluded from the clinical and research interest as well as from the benefit of osteoporosis management.

With the arrival of vaccines against the novel coronavirus in late 2020, the issue of how vaccines should be distributed and which groups should be prioritized has become salient. We study popular attitudes toward the distribution of COVID‐19 vaccines and how these have changed over the course of the pandemic in Switzerland, drawing on data from two rounds of an original public opinion survey conducted in the spring and winter of 2020. We find that the public supports prioritizing vulnerable groups such as health care workers or the elderly. We also find a notable degree of cross‐generational solidarity: younger age cohorts prioritize the elderly, while older groups prioritize (typically younger) health care workers. We then examine whether this finding is not in fact driven by vaccine hesitancy. This is not the case for older age groups, whose solidarity thus seems to be genuine. Vaccine hesitancy is an issue among younger groups, however.

Objective: We investigated the association of blood pressure with albuminuria and left ventricular hypertrophy (LVH) in young, middle and older age groups of patients. Design and method: Our study participants were treated patients with hypertension or diabetes, enrolled in a China nationwide registry. The 2510 patients were classified into young (&lt;45 years, n = 345), middle (45–65 years, n = 1383) and older (&gt;65 years, n = 782) age groups. Clinic blood pressure was measured three times consecutively on each of the two planned clinic visits. These six readings were averaged for statistical analysis. Albuminuria was defined as a urinary albumin-to-creatinine ratio of &gt; 30 mg/g. LVH was assessed by the electrocardiogram (ECG) Cornell product method. Results: The prevalence of albuminuria and ECG-LVH was 17.8% and 3.7%, respectively, in all patients and 18.1% and 4.2%, respectively, in 2026 (80.7%) patients on antihypertensive medication. The mean (±SD) systolic/diastolic blood pressure was 132.0 ± 16.5/85.2 ± 11.9 mmHg, 136.8 ± 17.9/81.7 ± 11.2 mmHg, and 139.8 ± 16.7/75.8 ± 10.4 mmHg in young, middle and older age groups. In the young age group, the prevalence of albuminuria increased from 8.8% in blood pressure &lt; 120/80 mmHg to 14.6%, 16.0% and 16.5% in blood pressure at 120–130/80–85, 130–140/85–90 and &gt; 140/90 mmHg. The corresponding values were 8.9%, 7.0%, 18.1% and 22.2%, respectively, in the middle age group, and 21.2%, 15.5%, 16.4% and 24.4%, respectively, in the older age group. The prevalence of ECG-LVH was slightly but non-significantly (P for trend &gt; 0.09) higher with increasing blood pressure similarly in all age groups. Conclusions: The relationship between blood pressure and organ damage seems to be age-dependent for albuminuria but not ECG-LVH.

The Registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Heart Transplantation Report—2015; Focus Theme: Early Graft Failure

Simple SummaryGallbladder cancer (GBC) is the most frequently diagnosed biliary tract cancer, associated with a poor prognosis due to its aggressive nature and insidious onset. Using data from the SEER database between the years 2011 and 2020, we analyzed the demographic factors and outcomes of 2724 patients who were diagnosed with metastatic gallbladder adenocarcinoma, the most common subtype of gallbladder carcinoma. The objective of this study was to investigate the demographic characteristics and assess the impact of bone metastasis on survival outcomes, as well as the effects of chemotherapy utilization in the presence of bone metastasis. Our results showed that patients with bone metastasis had significantly reduced overall survival rates compared to those without bone metastasis, particularly at younger ages. Furthermore, the utilization of chemotherapy was associated with improved survival outcomes in patients with bone metastasis.Background: Gallbladder carcinoma (GBC) is a rare, aggressive malignancy comprising 0.5% of gastrointestinal cancers. It has poor survival outcomes due to its insidious onset, lack of standardized screening, and limited therapies. Advanced-stage diagnosis with liver, lymph node, and peritoneal metastasis is common, while bone metastasis is rare. The knowledge on bone metastasis in GBC is limited to case reports and small series, and its clinical significance is largely unexplored. Methods: The study extracted the demographic and clinical variables of patients with metastatic (M1) gallbladder adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database between 2011 and 2020. Descriptive statistics were used to analyze the demographic characteristics. The multivariate Cox regression analysis was used to calculate the hazard ratio. The overall survival (OS) was assessed using the Kaplan–Meier method, and the log-rank test was utilized to compare the survival between the groups. Results: A total of 2724 patients were included in the study. A total of 69% of the patients were female, and the median age was 68 (range 24–90+). A total of 7.4% of the patients had bone metastasis on diagnosis. The multivariate Cox analysis identified bone metastasis as an independent mortality risk factor in metastatic GBC (HR 1.50, p < 0.001). The patients were divided into two age groups: a younger age group (18–74 years) and an older age group (75+ years). In the younger group, the median OS with and without bone metastasis was 3 and 5 months, respectively (p < 0.0001). In the older age group, there was no significant difference in the OS between the patients with and without bone metastasis (p = 0.35). In the younger group who were treated with chemotherapy, the patients with bone metastasis had a significantly worse OS (median OS 5 months vs. 8 months, p < 0.0001). In the untreated group, the patients with bone metastasis in the younger age group had a significantly worse OS (median OS 1 month vs. 2 months, p = 0.014). In the patients with bone metastasis, those who did not receive chemotherapy had a significantly worse OS than those who were treated with chemotherapy in both age groups (younger age group: median OS 1 month vs. 5 months, p < 0.0001 and older age group: median OS 1 month vs. 5 months, p = 0.041). Conclusions: Our findings suggest that the presence of bone metastasis in gallbladder adenocarcinoma is an independent prognostic factor associated with unfavorable survival outcomes in the younger age group (18–74 years). However, in the older age group (75+ years), the presence of bone metastasis did not impact the survival. Treatment with chemotherapy was associated with extended survival in all patients. Thus, early detection and aggressive management of bone metastasis, including the consideration of chemotherapy, may be crucial in improving the OS and quality of life for individuals with gallbladder adenocarcinoma.

HIV research in American youth.

The European Youth Heart Study (EYHS) addresses cardiovascular disease risk factors and their determinants in European children and adolescents. The Swedish part of the study began with cross-sectional data collection in 9- and 15-year-old schoolchildren in 1998–1999 (EYHS-I). Repeated observations of the key indicators were performed in 2004–2005 (EYHS-II). The purpose of this study was to assess potential dropout effects in EYHS-II. Participants in both EYHS-I and EYHS-II (n=459) were compared with dropouts who participated only in the EYHS-I (n=678) in relation to baseline physical activity, cardiorespiratory fitness and socioeconomic and anthropometric characteristics. Bivariate comparisons were performed using chi-square tests and gamma tests for nominal and ordinal data, respectively. Continuous data were compared by t tests and Mann−Whitney tests depending on the distribution. The Bonferroni correction was used to control for multiple hypothesis testing. Multiple logistic regression with backward elimination of variables was applied to study independent effects of variables on the probability of becoming a dropout. Analyses were performed separately for the younger and older age groups. The dropout proportion in EYHS-II was 60%. Subjects from the older age group were less likely to participate in the follow-up study (32% vs. 50%, p<0.001). In bivariate analyses, only maternal education was associated with dropout rates in the younger age group after Bonferroni correction. Males were more likely to drop out in both younger [odds ratio (OR)=1.72; 95% confidence interval (CI): 1.10, 2.96] and older (OR=1.96; 95% CI: 1.09, 3.54) age groups while basic maternal education was associated with outcome only in the younger group (OR=4.31; 95% CI: 1.78, 2.95) in regression analysis. The Swedish EYHS-II had high dropout rate after EYHS-I, but the dropouts did not differ from the participants in relation to physical activity, physical fitness, and anthropometric indices. Males were more likely to drop out than were females in both age groups. Differential dropout in relation to maternal education was observed in the younger age group.

Age and electromyographic frequency alterations during walking in children with cerebral palsy