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Background: Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide. Polypills, containing various combinations of medications for primary and secondary CVD prevention, have been developed to enhance medication adherence and reduce the healthcare burden of CVD. However, their effectiveness compared to usual care remains uncertain. Objective: This meta-analysis aimed to evaluate the effects of polypills on cardiovascular risk factors, major adverse cardiovascular events (MACE), and medication adherence. Methods: We conducted a comprehensive search for large-scale randomized controlled trials and observational studies comparing the effects of polypills versus usual care on CVD risk factors and events. Outcomes included changes in systolic and diastolic blood pressure (SBP, DBP), lipid profiles, occurrence of MACE, and medication adherence. Results: The use of polypills led to a statistically significant yet clinically modest reduction in SBP (mean difference -1.47 mmHg, 95% CI: -2.50 - -0.44, p<0.01) and DBP (mean difference1.10 mmHg, 95% CI: -1.68 - -0.51, p< 0.01) compared to usual care. Polypills also showed a significant reduction in the risk of MACE (RR: 0.86, 95% CI: 0.77 -0.95, p<0.01). There was a non-significant reduction in LDL and HDL levels. Adherence to medication improved by up to 17% in polypill users compared to those on usual care (p < 0.01). A multivariable metaregression analysis suggested that adherence may be the underlying factor responsible for the observed effect of the polypills on blood pressure. Conclusion: Polypills were found to significantly reduce SBP, DBP and MACE. An improvement in medication adherence was also observed among polypill users, which might be responsible for the significant reduction in SBP observed users. Future research might benefit from exploring a more personalized approach to the composition of polypills, which could reveal a more clinically significant impact of increased adherence on CVD outcomes.

Ever since its introduction as a diagnostic imaging tool the potential of magnetic resonance imaging (MRI) in radiation therapy (RT) treatment simulation and planning has been recognized. Recent technical advances have addressed many of the impediments to use of this technology and as a result have resulted in rapid and growing adoption of MRI in RT. The purpose of this article is to provide a broad review of the multiple uses of MR in the RT treatment simulation and planning process, identify several of the most used clinical scenarios in which MR is integral to the simulation and planning process, highlight existing limitations and provide multiple unmet needs thereby highlighting opportunities for the diagnostic MR imaging community to contribute and collaborate with our oncology colleagues.Evidence Level5Technical EfficacyStage 5

Abstract Telehealth is a broad concept that refers to any delivery of health care in real time using technologies to connect people or information that are not in the same physical location. Until fairly recently, telehealth was more aspiration than reality. This situation changed radically due in part to the COVID-19 pandemic, which led to a near-overnight inability for patients to be seen for routine management of chronic health conditions, including those with cancer. The purpose of this brief narrative review is to outline some areas where emerging and future technology may allow for innovations with specific implications for people with a current or past diagnosis of cancer, including underserved and/or historically excluded populations. Specific topics of telehealth are broadly covered in other areas of the special issue.

Melanoma diagnosed within 1 year of pregnancy is defined as pregnancy-associated melanoma (PAM). No robust data on how pregnancy influences melanoma nor guidelines for PAM management exist. With IRB approval, female patients with a pathology-confirmed melanoma diagnosis within 1 year of pregnancy treated at our institution from 2000 to 2020 were identified. Controls from the cancer registry were matched 1 : 4 when available on decade of age, year of surgery (±5), and stage. We identified 83 PAM patients with median follow-up of 86 months. Mean age at diagnosis was 31 years. 80% AJCC V8 stage I, 2.4% stage II, 13% stage III, 4.8% stage IV. Mean Breslow thickness was 0.79 mm and 3.6% exhibited ulceration. The mean mitotic rate was 0.76/mm 2 . In terms of PAM management, 98.6% of ESD patients and 86.7% of LSD patients received standard-of-care therapy per NCCN guidelines for their disease stage. No clinically significant delays in treatment were noted. Time to treatment from diagnosis to systemic therapy for LSD patients was an average of 46 days (95% CI: 34–59 days). Comparing the 83 PAM patients to 309 controls matched on age, stage, and year of diagnosis, similar 5-year overall survival (97% vs. 97%, P = 0.95) or recurrence-free survival (96% vs. 96%, P = 0.86) was observed. The outcomes of PAM following SOC treatment at a highly specialized center for melanoma care were comparable to non-PAM when matched by clinical-pathologic features. Specialty center care is encouraged for women with PAM.

SUMMARY The third carpal bone (C 3 ) was collected from both forelimbs of 27 Thoroughbreds. On the basis of age, training, and history, specimens were assigned to 1 of 5 groups: yearling, untrained horses (group 1, n = 4); 2- to 3-year-old, untrained horses (group 2, n = 7); trained 2-year-old horses (group 3, n = 6); trained 3-year-old horses (group 4, n = 6); and 3-year-old, trained horses with carpal pathologic features (group 5, n = 4). A transverse section of subchondral bone 5-mm thick was cut in a precise fashion 10 mm below the proximal articular surface of all specimens. After high-detail radiography was done, indentation testing was performed on the proximal surface of the section at points 5 mm apart. The stiffness of the subchondral cancellous bone was determined from the slope of the load vs displacement curve. Topographic plots of stiffness measurements were compared with radiographs of each specimen. Point determinations were averaged to derive measures for the radial and intermediate facets, and for regions 5, 10, 15, and 20 mm from the dorsal margin of C 3 . Area fraction (1-p; p = porosity) was measured for the radial and intermediate facets, using an automated image analysis system. Significant ( P < 0.05) increases in stiffness and area fraction were found in the C 3 from trained horses (groups 3 to 5), compared with untrained horses (groups 1 to 2). Stiffness and area fraction of the radial facet of pathologic C 3 were significantly higher than the same variables measured in C 3 from any other group. A typical profile of regional subchondral stiffness was identified in C 3 from normal horses, with maximal stiffness measured 10 mm from the dorsal articular margin. A different pattern was found in pathologic C 3 , with significantly greater stiffness 15 and 20 mm from the dorsal articular margin when compared with normal horses. A highly significant ( P < 0.0001) direct linear correlation between stiffness and area fraction at the radial facet was found. Topographic and radiographic analysis demonstrated good correlation between stiffness and radiographic density of the bone sections. The observed patterns of normal and pathologic C 3 were contrasted. In particular, a large gradient in subchondral stiffness was identified in pathologic C 3 at the dorsomedial aspect of the bone.

Importance Living kidney donors may have an increased risk of fractures due to reductions in kidney mass, lower concentrations of serum 1,25-dihydroxyvitamin D, and secondary increases in serum parathyroid hormone. Objective To compare the overall and site-specific risk of fractures among living kidney donors with strictly matched controls from the general population who would have been eligible to donate a kidney but did not do so. Design, Setting, and Participants This survey study was conducted between December 1, 2021, and July 31, 2023. A total of 5065 living kidney donors from 3 large transplant centers in Minnesota were invited to complete a survey about their bone health and history of fractures, and 16 156 population-based nondonor controls without a history of comorbidities that would have precluded kidney donation were identified from the Rochester Epidemiology Project and completed the same survey. A total of 2132 living kidney donors and 2014 nondonor controls responded to the survey. Statistical analyses were performed from May to August 2023. Exposure Living kidney donation. Main Outcomes and Measures The rates of overall and site-specific fractures were compared between living kidney donors and controls using standardized incidence ratios (SIRs). Results At the time of survey, the 2132 living kidney donors had a mean (SD) age of 67.1 (8.9) years and included 1245 women (58.4%), and the 2014 controls had a mean (SD) age of 68.6 (7.9) years and included 1140 women (56.6%). The mean (SD) time between donation or index date and survey date was 24.2 (10.4) years for donors and 27.6 (10.7) years for controls. The overall rate of fractures among living kidney donors was significantly lower than among controls (SIR, 0.89; 95% CI, 0.81-0.97). However, there were significantly more vertebral fractures among living kidney donors than among controls (SIR, 1.42; 95% CI, 1.05-1.83). Conclusions and Relevance This survey study found a reduced rate of overall fractures but an excess of vertebral fractures among living kidney donors compared with controls after a mean follow-up of 25 years. Treatment of excess vertebral fractures with dietary supplements such as vitamin D 3 may reduce the numbers of vertebral fractures and patient morbidity.

PURPOSE Patients with biochemically recurrent prostate cancer (BRPC) after radical prostatectomy and a short PSA doubling time are at risk for distant metastases. Apalutamide, an androgen receptor antagonist, and abiraterone acetate plus prednisone (AAP) prolong survival in the metastatic setting. We evaluated whether intensification of androgen-deprivation therapy (ADT) improves outcomes in BRPC. PATIENTS AND METHODS PRESTO is a randomized phase III, open-label trial in patients with BRPC and PSA doubling time ≤9 months (ClinicalTrials.gov identifier: NCT03009981 ). Patients were randomly assigned 1:1:1 to receive a finite 52-week treatment course with ADT control, ADT + apalutamide, or ADT + apalutamide + AAP. The primary end point was PSA progression-free survival (PSA-PFS), defined as serum PSA >0.2 ng/mL after treatment completion. RESULTS Five hundred three patients were enrolled. The median PSA was 1.8 ng/mL (IQR, 1.0-3.6). At the first planned interim analysis, both experimental arms significantly prolonged PSA-PFS compared with the control arm (median, 24.9 months for ADT + apalutamide v 20.3 months for ADT; hazard ratio [HR], 0.52 [95% CI, 0.35 to 0.77]; P = .00047; median, 26.0 months for ADT + apalutamide + AAP v 20.0 months for ADT; HR, 0.48 [95% CI, 0.32 to 0.71]; P = .00008). Median time to testosterone recovery did not differ across treatment arms. The most common grade ≥3 adverse event was hypertension (7.5%, 7.4%, and 18% in ADT, ADT + apalutamide, and ADT + apalutamide + AAP arms, respectively). CONCLUSION Intensified AR blockade for a finite duration prolongs PSA-PFS with a manageable safety profile, without adversely affecting time to testosterone recovery. The addition of apalutamide to ADT should be considered in patients with high-risk BRPC.

Sickle cell disease (SCD) is a chronic hematologic disorder which causes progressive cerebral arteriopathy beginning in childhood. As a result, arterial ischemic stroke is a major cause of morbidity and mortality in SCD, and SCD is a leading cause of childhood stroke worldwide. Allogenic hematopoietic stem cell transplant (HSCT) may be curative for individuals with SCD. Long-term outcomes and effects are currently being studied. In this report, we describe a child with SCD who presented with arterial ischemic stroke at 6 years of age and was found to have a severe form of cerebral large vessel arteriopathy by catheter-directed angiography. The patient initially underwent revascularization surgery by indirect superficial temporal artery to middle cerebral artery bypass, and 1 year later, he underwent curative HSCT. Approximately 3 years after HSCT, repeat catheter-directed angiography revealed a striking reversal of cerebral large vessel arteriopathy. This article reveals a previously unrecognized and potentially beneficial effect of HSCT that may ameliorate cerebral large vessel arteriopathy and improve cerebrovascular health for children with SCD.