Citations

Abstract Purpose Elective genomic sequencing (EGS) returns monogenic disease findings in multiple genes, including potentially novel variants, and may also provide participants with carrier status, pharmacogenomic and other health-related information. The PeopleSeq Study assessed participants’ motivations for and concerns about EGS and the associated clinical and psychosocial outcomes across diverse EGS providers. Methods We administered a shared questionnaire to participants who chose to undergo EGS via 18 academic, clinical, or commercial EGS platforms. Results We enrolled 1575 participants, of whom 1147 (72.8%) completed a questionnaire after receiving their EGS results. A majority (60.3%) of the participants who completed a post-result questionnaire self-reported receiving results they assessed as important, including negative findings, and 75.9% reported a form of health-related utility. Among a subset (19.4%) who shared their EGS reports, 16.6% (37 of n =223) received a monogenic finding and self-reported results deemed “important” were consistent with EGS reports. Most participants (74.1%) discussed their results with their family, but fewer discussed their results with a healthcare provider other than the site team (41.7%) or had one or more medical visits as a direct result of their EGS testing (23.1%). Participants expressed diverse motivations for EGS, with 91.4% expressing interest in their personal disease risk and 54% who expressed quasi-indication-based motivations related to family medical history. Individuals motivated by family history reported important results at a significantly higher rate. Conclusions Early adopters of EGS are motivated by general interest in their health as well as quasi-indication-based considerations such as family history. A majority of participants learned results they considered medically important, but a much smaller segment engaged healthcare providers with their results.

Importance Currently, there are no standardized outcome domains or measures in clinical trials for facial aging. Heterogeneity in outcome domains and measurement instruments across clinical trials creates difficulty in directly comparing interventions, determining superior therapies, and developing high-quality meta-analyses. Objective To develop a core outcome set (COS) of essential domains to be reported in clinical trials evaluating the efficacy of interventions for facial aging. Evidence Review PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from September 2005 to September 2015. An updated search of the same databases was performed from September 2015 to February 2026. Studies were included if (1) they were randomized clinical trial or controlled clinical trial in design, (2) they assessed the efficacy or safety of an intervention for facial aging, (3) they were published in English, and (4) they involved human participants. Complementary sources, including patient interviews, were used to capture further relevant outcomes. Two rounds of Delphi surveys, followed by consensus meetings, were used to identify outcome domains considered most important by both patient and physician stakeholders. Findings The final COS consists of 6 outcome domains: (1) overall convenience of treatment; (2) time to return to normal work and social activity; (3) overall assessment of focused area of treatment (at the point in time when treatment is expected to provide peak benefit); (4) duration of treatment effect; (5) severity of persistent local or systemic adverse events, including pigmentary change, skin texture change, delayed healing, scarring, and serious adverse events; and (6) patient satisfaction with treatment. Conclusions and Relevance The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.

Abstract Background The tumor, node, metastasis (TNM) classification at pathological evaluation determines prognosis following cancer treatment. For rectal cancer patients undergoing neoadjuvant therapy, whether ypTNM likely confers different prognosis than pTNM. We compared survival outcomes of patients classified by ypTNM vs pTNM staging. Methods Patients with resected locoregional rectal cancer from the National Cancer Database who underwent upfront surgery (pTNM) and had ≥5 years follow-up (2010-2017) were compared with those receiving neoadjuvant therapy followed by surgery (ypTNM). To address treatment selection bias, analyses were stratified by receipt of guideline-concordant care. Overall survival (OS) was compared using Kaplan-Meier and multivariable Cox regression analyses. Results Of 50 436 patients (median age = 60; 61.4% male), 11 732 (23.3%) underwent upfront surgery and 38 704 (76.7%) received neoadjuvant therapy; 78.8% of the upfront surgery group received guideline-concordant care. In analyses stratified by guideline-concordant care, overall survival was similar for stage 0-I (hazard ratio [HR] = 1.05; 95% CI = 0.96 to 1.15) but significantly worse for ypTNM vs pTNM in stage II (HR = 1.50; 95% CI = 1.27 to 1.77; 5-year OS = 75.6% vs 83.2%) and stage III (HR = 1.60; 95% CI = 1.46 to 1.75; 5-year OS = 67.0% vs 78.2%). Multivariable analysis confirmed ypTNM was associated with worse survival at each stage (stage 0-I: HR = 1.14, P = .004; stage II: HR = 1.49, P < .001; stage III: HR = 1.60, P < .001). Conclusion Stage for stage, ypTNM classification is associated with worse survival than pTNM classification, with increasing difference at higher stages. Future staging systems and management guidelines should account for these differences to optimize prognostication and stratification for clinical trials and surveillance strategies.

Background: Achilles tendon ruptures are among the most debilitating injuries in professional basketball, often leading to prolonged absence and long-term performance decline. While calf strains are common among National Basketball Association (NBA) athletes, their role as a precursor to Achilles rupture remains poorly understood. Hypothesis: A previous calf strain would be associated with increased odds of Achilles tendon rupture in NBA players and that affected players would experience significant post-injury performance declines. Study Design: Case-cohort study; Level of evidence, 3. Methods: Publicly available data on NBA players from 1958 to 2024 were analyzed, with the data search conducted in June 2025. Players with Achilles ruptures (n = 60) were compared with players with calf strains who did not sustain a rupture (n = 258). Logistic regression adjusted for age, body mass index, position, starter status, and workload. Pre- and postinjury performance was evaluated over 2 seasons using paired t tests. Descriptive analyses characterized injury laterality, game context, quarter, shoe type, and draft position. Video review assessed injury mechanisms. Results: Previous calf strain was associated with increased odds of Achilles rupture (odds ratio, 2.49; 95% CI, 1.16-5.22; P = .02). Among those with both injuries, 85.7% occurred on the same side, with a mean interval of 1.9 years. Of all players, a total of 75% returned to play. Postinjury declines were observed in player efficiency rating (−2.46), win shares (−3.23), games played (−260.3), and minutes per game (−5.19) (all P < .001). Return was more likely in younger players and those on multiyear contracts. Video analysis revealed a consistent “false step” mechanism in 95% of cases with footage. Most Achilles tendon ruptures occurred during in-game activity, while shoe type was evaluated descriptively and was not associated with player position or preinjury workload. Conclusion: Our study showed that previous calf strain is associated with an increased risk of Achilles tendon rupture in NBA players and may serve as a clinically identifiable risk marker. Rupture leads to substantial and sustained performance decline, even among those who return. Targeted rehabilitation and movement retraining may help mitigate progression to rupture in high-risk athletes.

Breast size changes are common, but the underlying cause may be challenging to diagnose and requires a structured approach combining patient history, physical examination, and multimodality imaging to differentiate benign from malignant causes and improve patient outcomes.

The primary aim of this study was to examine pitching performance metrics before and after ulnar collateral ligament reconstruction (UCLR) among Major League Baseball (MLB) starting and relief pitchers. The following information was extracted from the “Tommy John Surgery List” database regarding UCLR surgeries among MLB pitchers: UCLR date, pitcher type (starting pitcher, relief pitcher), and age at time of UCLR. Pitching performance metrics were extracted from the Baseball Savant online platform for the two seasons immediately prior to UCLR (pre) and the two seasons immediately following returning to pitching after UCLR (post). Fifty-nine pitchers were included in this study (29 starting pitchers, 30 relief pitchers). The outcome measures included the number of pitches thrown, earned run average (ERA), walks plus hits per inning pitched (WHIP), strikeout percentage, whiff percentage, walk percentage, batting average against, ground ball percentage, and fastball velocity. There was a pitcher type-by-time interaction effect for ERA (p = 0.01; η2 = 0.12) and WHIP (p = 0.01; η2 = 0.12). Starting pitcher ERA increased from 3.68 to 4.40 from pre- to post-surgery, while relief pitcher ERA decreased from 4.47 to 3.90. In addition, starting pitcher WHIP increased from 1.22 to 1.29 from pre- to post-surgery, while relief pitcher WHIP decreased from 1.38 to 1.28. There was a main effect of time for pitches thrown (p = 0.04; η2 = 0.07). Significant differences between starting and relief pitchers were observed for changes in ERA and WHIP following UCLR, whereas no pitcher type-by-time interactions were observed for the remaining performance metrics. Both starting and relief pitchers threw fewer pitches following UCLR, while fastball velocity and other key pitching performance metrics remained largely unchanged.