Citations

During a 3-year period, 51 patients with upperextremity reflex sympathetic dystrophy were studied. Of 20 patients managed by conservative methods, nine (45%) showed signs of improvement 3 years after onset of the syndrome. Of 31 patients treated with repeated stellate ganglion blocks, 23 (74%) had improved at the 3-year evaluation. Management of both the potential causes and the symptoms of reflex sympathetic dystrophy is necessary. Although sympathetic blocks failed to improve all cases, they should be considered as one of the important methods for the management of reflex sympathetic dystrophy.

Abstract Context The impact of active hypercortisolism on sleep is incompletely characterized. Studies report impaired sleep in patients with Cushing syndrome (CS). Patients with mild autonomous cortisol secretion (MACS) demonstrate mild nocturnal hypercortisolism that could impact sleep. Objectives To characterize sleep abnormalities in patients with CS and MACS using the Pittsburgh Sleep Quality Index (PSQI), identify factors associated with poor sleep, and compare sleep abnormalities in patients with MACS vs referent subjects. Methods We conducted a single-center cross-sectional study of adults with active CS and MACS. Clinical and biochemical severity scores for hypercortisolism were calculated. Parallelly, we enrolled referent subjects. Quality of life was assessed using (1) the Short Form-36 (SF-36) in all participants and (2) the CushingQoL in patients with active hypercortisolism. Sleep quality was assessed using PSQI. Results PSQI was assessed in 154 patients with CS (mean 12, SD ±4.5), 194 patients with MACS (mean 11, SD 4.6), and 89 referents (mean 5, SD ±3.4). Patients with MACS exhibited shorter sleep duration, longer sleep latency, more severe daytime dysfunction, lower sleep efficiency, and a higher sleep medication use compared to referent subjects (P = <.001 for all). Age-, sex, and body mass index-adjusted analysis demonstrated no differences in PSQI or its subcomponents between patients with CS and MACS (P > .05 for all). In a multivariable analysis of patients with MACS, younger age, female sex, and higher clinical hypercortisolism severity score were associated with impaired sleep. In patients with CS, only younger age was associated with poor sleep. Conclusion Patients with MACS demonstrate sleep impairment that is similar to patients with CS. Younger women with higher clinical severity of MACS are more likely to have impaired sleep.

Objectives The purpose of the current study was to evaluate differences in total sleep time and heart rate variability (HRV) in active-duty firefighters between on-shift and off-shift days. Methods 59 structural firefighters (age: 37.3±7.3 years; height: 1.80±0.08 m; weight: 88.9±14.1 kg and body mass index (BMI): 27.5±4.1 kg/m2) participated in this longitudinal observation study. Each morning for 15 weeks, firefighters were asked to sync a smart ring with a smartphone application to download night-time data, which were then extracted to a cloud-based software application for later analysis. The software also computed a readiness score each morning. All day types were coded as on-shift or off-shift. Results The average nightly sleep time for all firefighters was 6.95±1.24 hours. When off-shift, firefighters recorded more sleep compared with on-shift nights (off-shift: 6.97±0.50 hours vs on-shift: 6.68±0.52 hours; p<0.0001). HRV (p<0.0001) and readiness scores (p=0.02) were lower off-shift compared with on-shift. For the lagged correlation analysis, total sleep time was moderately positively correlated with the following day’s readiness score. Conclusions Firefighters recorded more total sleep time when off-shift compared with on-shift; however, HRV and readiness scores were higher on-shift. The lag-time correlations indicate an association between sleep time and HRV or readiness scores, with approximately half of the variability in readiness being attributable to changes in total sleep time, which highlights the complexity of the readiness and HRV signals/systems.

Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive liver disease characterized by complex interactions between lipotoxicity, ER stress responses, and immune-mediated inflammation. We identified enrichment of the proinflammatory alarmin S100 calcium-binding protein A11 (S100A11) on extracellular vesicles stimulated by palmitate-induced lipotoxic ER stress with concomitant upregulation of hepatocellular S100A11 abundance in an IRE1A-XBP1s–dependent manner. We next investigated the epigenetic mechanisms that regulate this stress response. Publicly available human liver ChIP-Seq GEO datasets demonstrated a region of histone H3 lysine 27 (H3K27) acetylation upstream of the S100A11 promoter. H3K27 acetylation ChIP-qPCR demonstrated a positive correlation between lipotoxic ER stress and H3K27 acetylation of the region, which we termed the lipotoxicity-influenced enhancer (LIE) domain. CRISPR-mediated repression of the LIE domain reduced palmitate-induced H3K27 acetylation and corresponding S100A11 upregulation in Huh7 cells and immortalized mouse hepatocytes. Silencing of the murine LIE in 2 independent steatohepatitis models demonstrated reduced S100a11 upregulation and attenuated liver injury. We confirmed H3K27 acetylation and XBP1s occupancy at the LIE domain in human MASH liver samples and an increase in hepatocyte-derived S100A11-enriched extracellular vesicles in MASH patient plasma. Our studies demonstrate a LIE domain that mediates hepatic S100A11 upregulation. This pathway may be a potential therapeutic target in MASH.

Objectives: There is a paucity of research comparing the outcomes of medial ulnar collateral ligament (MUCL) repair with internal bracing to isolated MUCL reconstruction in professional baseball players. Further, the practice of supplementing a MUCL reconstruction with an internal brace, a "hybrid" reconstruction, has increased in the surgical treatment of MUCL injuries for professional baseball players, without any currently known published research defining the clinical outcomes of this modification. We sought to investigate the trends and outcomes of MUCL repair with internal bracing and "hybrid" MUCL reconstruction with internal bracing. Using a matched cohort analysis, we also sought to compare the clinical outcomes of both MUCL repair with internal bracing and "hybrid" MUCL reconstruction with internal bracing to isolated MUCL reconstructions, without internal bracing, in professional baseball players. Methods: The MLB Health and Injury Tracking System was used to identify all professional baseball players who underwent MUCL surgery, regardless of surgery technique, from 2010 to 2023. Professional players of all levels (MLB and MiLB) and players of all positions were included. Player demographics, injury characteristics, surgical details, and postoperative outcomes were obtained. Player demographics included age at surgery, position of play, professional level of play and surgical technique. Outcomes assessed were return to play (RTP) status, time to RTP, return to same level of play (RTSL), time to RTSL, revision MUCL surgery, and time to revision MUCL surgery, with a minimum of 2 years of follow up. Players were considered to have RTP if they participated in at least one game at any professional level. RTSL was defined as returning to the same league of professional play or higher. Patients undergoing MUCL repair and "hybrid" MUCL reconstruction with internal bracing were independently compared to propensity matched patients undergoing isolated MUCL reconstruction, without internal bracing, to assess for a difference in postoperative outcomes. Four subgroup analyses were conducted by further categorizing patients to MLB players, MiLB players, pitchers, and position players. Results: 76 patients underwent MUCL repair with internal bracing from 2016-2021 and were successfully propensity matched to 76 patients undergoing isolated MUCL reconstructions. Baseline patient demographic variables of MUCL repairs were statistically similar to those of controls except for age at time of surgery (24.5 vs 21.8; p<0.001). 81 patients underwent "hybrid" MUCL reconstructions with internal bracing from 2016-2021 and were successfully propensity matched to 81 patients undergoing isolated MUCL reconstructions. Baseline demographic variables of "hybrid" MUCL reconstructions were statistically similar to those of controls except for age at time of surgery (24.3 vs. 23.3; p=0.006). Compared to isolated MUCL reconstruction controls, all patients undergoing MUCL repair demonstrated significantly shorter time to RTP (mean 421.2 vs. 546.2 days; p<0.001), shorter time to RTSL (mean 436.2 vs. 558.8 days; p<0.001), and shorter time to revision (mean 465.2 vs.1648 days; p=0.036). The number of patients who RTP at any level, RTSL, and number of revision surgeries were not significantly different. Compared to isolated MUCL reconstruction controls, all patients undergoing "hybrid" MUCL reconstructions demonstrated no significant differences with respect to the number of patients who RTP, time to RTP, number of patients who RTSL, days to RTSL, number of revision surgeries, and time to revision surgery. In MLB players only, compared to isolated MUCL reconstruction controls, patients who underwent MUCL repairs demonstrated significantly shorter time to RTP (mean 282.8 vs 507.3 days; p=0.008) and shorter time to RTSL (mean 299.7 vs. 598.0 days; p = 0.024). No other outcomes were significant. In MLB players only, compared to isolated MUCL reconstruction controls, patients who underwent "hybrid" MUCL reconstructions demonstrated significantly shorter time to RTP (mean 436.2 vs. 525.3 days; p=0.026). No other outcomes were significant. In MiLB players only, compared to isolated MUCL reconstruction controls, patients who underwent MUCL repairs demonstrated significantly shorter time to RTP (mean 444.3 vs 550.7 days; p<0.001) and shorter time to RTSL (mean 451.7 vs. 556.5 days; p<0.001). No other outcomes were significant. In MiLB players only, compared to isolated MUCL reconstruction controls, patients who underwent "hybrid" MUCL reconstructions demonstrated no significant differences in outcomes. In evaluating pitchers only, compared to isolated MUCL reconstruction controls, patients undergoing MUCL repair demonstrated significantly shorter time to RTP (mean 421.7 vs. 578.6 days; p<0.001), shorter time to RTSL (mean 434.8 vs. 591.6 days; p <0.001), and shorter time to revision surgery (mean 465.2 vs.1648 days; p=0.036). No other outcomes were significant. In pitchers only, compared to isolated MUCL reconstruction controls, patients undergoing "hybrid" MUCL reconstructions demonstrated significantly shorter time to RTP (mean 488.1 vs. 549.0 days; p=0.013) and shorter time to RTSL (mean 505.7 days vs. 577.0 days, respectively; p=0.021). No other outcomes were significant. Notably, all revision surgeries in occurred in pitchers only. Conclusions: Based on a matched cohort anaylsis of professional baseball players undergoing MUCL surgery, when compared to an isolated MUCL reconstruction, MUCL repair with internal bracing may allow for a shorter time to RTP and RTSL, with a shorter time to revision surgery. For pitchers, "hybrid" MUCL reconstruction may allow for a shorter time to RTP and RTSL. For MLB players, "hybrid" MUCL reconstruction may allow for a shorter RTP.

Objectives: The number of medial ulnar collateral ligament (MUCL) reconstructions are increasing. The epidemiology surrounding revision MUCL reconstructions in professional baseball players has not been well defined. The purpose of this study was to report the epidemiology of revision MUCL reconstruction in professional baseball players. The authors hypothesized that the number of revision MUCL reconstructions would increase over time and that the return to sport rate at the same level of play would be less than 70%. Methods: All professional baseball pitchers who underwent revision MUCL reconstruction between 2010-2023 were identified using the MLB Health and Injury Tracking System (HITS). Rate of return and time to return to play (RTP) and return to same level of play (RTSL) was recorded and analyzed for pitchers with a minimum follow up of 2 years. Surgical variables including technique and graft choice were also recorded. Results: Overall, 191 pitchers (avg age 26.0 years), underwent revision MUCL reconstruction. The average time between primary and revision surgery was 1,381 days (45 months). 130 (68%) of these players were MLB pitchers and the other 61 (32%) were MiLB pitchers. 59% of pitchers were able to RTSL at an average of 604 ± 250 days after surgery. 2023 was the year with most revision MUCL reconstructions (n = 27) and the fewest reconstructions were performed in 2010 and 2011 (n = 4). Monthly distribution demonstrates the highest surgery months to be May (17%), June (20%), and July (17%). Hamstring tendon autograft was found to be the most commonly used graft source (n = 90, 47%), compared to palmaris longus autograft (n = 67, 35%). No significant differences were found in the types of grafts used over time ( P = .238 for palmaris and P = .133 for hamstring). In terms of tunnel configuration, both the Modified Jobe and Docking techniques were used in equal occurrence (n = 70, 37%) Conclusions: Following revision MUCL reconstruction, only 72% of professional baseball pitchers were able to return to play at any level at an average of 556 days (18 months), and only 59% were able to return to the same level of play at an average of 604 days (20 months). The average time between primary and revision MUCL reconstruction was 45 months (3.75 years). Pitchers should be counseled on the relatively low RTSL rate and the prolonged time to RTSL.

Objectives: There are few studies that have closely evaluated the outcomes of ulnar collateral ligament repair and reconstruction (UCLR) in position players (PP). The objective of this study was to determine the outcome of UCLR in professional baseball players who play in non-pitcher positions, i.e. PP. Methods: The approval of the Major League Baseball (MLB) Research Committee was obtained. All PP who underwent surgery for their UCL while active on an MLB or Minor League Baseball (MiLB) team were identified using The MLB Health and Injury Tracking System. PP who underwent UCLR from 2010 to 2023 were analyzes, however for data that concerned PP time to return to professional play, only players who underwent UCL surgery from 2010 to 2021 were evaluated in order to ensure the presence of a minimum of 2-year follow-up data. Return to play (RTP) was defined as a player who played in at least 1 game at any professional level (A, AA, AAA, or MLB). Players were deemed to return to the same level of play (RTSLP) if they played in at least 1 game at the same competition level or higher that they played in prior to their UCL surgery. PP who had a time to RTP or a time to RTSLP that exceeded 800 days were excluded from any analysis that concerned the time to return to play. PPs were also compared to a cohort of professional baseball pitchers who had also undergone UCL surgery. Results: From 2010 to 2023, 241 PP underwent surgery for their UCL at a mean age of 23.4 ± 4.3 years old (Table 1). Overall, PP had their UCL surgery at approximately a mean of 3.7 ± 3.3 years after the start of their professional career (Table 1). Further, apart from the year 2020, the annual number of UCL surgeries performed in MLB and MiLB PP demonstrated an upward trend from 2010 to 2023, although no trends in the distribution of UCL surgeries across position type or between major and minor players exist. No statistically significant differences in RTP nor RTSLP rates following UCL surgery in PP existed when comparing across position type (catcher vs. infielder vs. outfielder) and across surgery type (repair vs. reconstruction vs. reconstruction with augmentation) (Table 2). PP who underwent repairs were able to RTP at a median of 221 days (IQR: 81), which was sooner than PP who underwent reconstruction surgery (median: 383 days, IQR: 316) or reconstructions with augmentation (median: 456 days, IQR: 219) (P = 0.002) (Table 3). PP with UCL repairs were also able to RTSLP sooner (median: 234 days, IQR: 64) than PP who underwent reconstructions (median: 394 days, IQR: 305) or reconstructions with augmentation (median: 462 days, IQR: 242) ( P = 0.003) (Table 3). Further, infielders RTP sooner (median: 335 days, IQR: 157) than catchers (median: 396 days, IQR: 283) and outfielders (median: 412 days, IQR: 366) ( P = 0.036) (Table 3). Similarly, infielders RTSLP sooner (median: 334 days, IQR: 162) than catchers (median: 470 days, IQR: 281) and outfielders (median: 426 days, IQR: 354) ( P = 0.016) (Table 3). Following UCL surgery, PP were able to RTSLP, on average, more than 2 months sooner than pitchers (429 ± 177 days for PP vs 499 ± 153 days for pitchers, P < 0.001). PP who underwent repair of their UCL were able to RTSLP over 4.5 months, on average, sooner than pitchers who underwent UCL repair (269 ± 125 days for PPs vs 405 ± 153 days for pitchers, P < 0.001) and PP who underwent reconstruction of their UCL were able to RTSLP just under 50 days sooner than pitchers who had their UCLs reconstructed (450 ± 175 days for PPs vs 498 ± 151 days for pitchers, P < 0.001) (Figure 1). Conclusions: Few studies have examined PP outcome data following UCLR surgery. As such, there is little understanding as to the differences in return to game rates between various baseball non-pitcher positions as well as the differences in the time it takes to RTP and RTSLP. This study highlights that the annual number of UCLR surgeries demonstrates an upward trend. This retrospective analysis also highlights that PP with UCL repairs were able to RTP and RTSLP sooner than PP who underwent UCL reconstructions and UCL reconstructions with augmentation. Furthermore, infielders were able to RTP and RTSLP sooner than catchers as well as outfielders. The results of this study demonstrate that the type of UCL surgery as well as the player’s position does not seem to significantly impact whether or not a player actually returns to playing professional baseball, however it does impact the speed at whichthey are able to return (provided they do return to playing baseball). As such, the results of this study may be used to counsel PP regarding speed at which a return to playing baseball can be expected.

The FAITH! (Fostering African-American Improvement in Total Health) Cardiovascular Health and Wellness Program is more than a decade-long community-based participatory research initiative aimed at addressing cardiovascular health disparities among African-Americans in Minnesota. Founded in 2013, the program employs a culturally tailored, community-driven approach by partnering with African-American faith communities to promote cardiovascular health through education, digital health tools, and multilevel interventions targeting the social determinants of health. Grounded in community-based participatory research principles, FAITH! prioritizes equitable academic-community partnerships, co-learning, community capacity building, and shared ownership in all aspects of research and implementation. The program’s exemplary innovations include the NIH-funded FAITH! Trial, a randomized clinical trial, testing a mobile health intervention (the FAITH! App) co-created with the African-American community, and the Techquity by FAITH! study. Techquity by FAITH! evaluates the effectiveness of a culturally relevant, community-informed mHealth intervention supported by a Digital Health Advocate network to improve overall cardiovascular health and digital health literacy. During its evolution, FAITH! has addressed emergent public health crises, including the COVID-19 pandemic, by adapting programming to provide emergency preparedness resources, health education, and vaccine outreach. Key outcomes include sustainable church-based health ministries, increased research participation, and successful translation of research into practice. The program has also contributed to research workforce development by mentoring and training diverse early-career scholars and community leaders in community-based participatory research and cardiovascular health equity research. Lessons learned highlight the transformative impact of community-based participatory research in building trust, facilitating culturally relevant dissemination, and sustaining health equity initiatives. The FAITH! model demonstrates a scalable, community-led strategy for advancing cardiovascular health in underserved populations and provides a blueprint for future initiatives aiming to reduce racial health disparities.

Importance Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid β (Aβ) pathology. Objective To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]). Design, Setting, and Participants This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET Aβ biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964). Exposures Plasma p-tau217 levels measured by immunoassay. Main Outcome and Measures Aβ status, determined by CSF or Aβ PET biomarkers. Results Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90]; P = .12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90]; P &amp;lt; .001) and true Aβ-positive detection rate (49% [95% CI, 43-55] vs 69% [95% CI, 64-75]; P &amp;lt; .001). Conclusions and Relevance The findings highlight the potential of plasma p-tau217 as a stand-alone test—or when used in a sequential 2-step approach alongside PET or CSF testing—as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.

This review explores how multimodal foundation models (MFMs) are transforming biliary tract cancer (BTC) research. BTCs are aggressive malignancies with poor prognosis, presenting unique challenges due to difficult diagnostic methods, molecular complexity, and rarity. Importantly, intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA), and distal bile duct cholangiocarcinoma (dCCA) represent fundamentally distinct clinical entities, with iCCA presenting as mass-forming lesions amenable to biopsy and targeted therapies, while pCCA manifests as infiltrative bile duct lesions with challenging diagnosis and primarily palliative management approaches. MFMs offer potential to advance research by integrating radiological images, histopathology, multi-omics profiles, and clinical data into unified computational frameworks, with applications tailored to these distinct BTC subtypes. Key applications include enhanced biomarker discovery that identifies previously unrecognizable cross-modal patterns, potential for improving currently limited diagnostic accuracy—though validation in BTC-specific cohorts remains essential—accelerated drug repurposing, and advanced patient stratification for personalized treatment. Despite promising results, challenges such as data scarcity, high computational demands, and clinical workflow integration remain to be addressed. Future research should focus on standardized data protocols, architectural innovations, and prospective validation studies. The integration of artificial intelligence (AI)-based methodologies offers new solutions for these historically challenging malignancies. However, current evidence for BTC-specific applications remains largely theoretical, with most studies limited to proof-of-concept designs or related cancer types. Comprehensive clinical validation studies and prospective trials demonstrating patient benefit are essential prerequisites for clinical implementation. The timeline for evidence-based clinical adoption likely extends 7–10 years, contingent on successful completion of validation studies addressing current evidence gaps.