Citations

Abstract Background The incidence of type 2 diabetes mellitus among young adults has been increasing over the past few decades. There are limited data on contemporary national cardiovascular mortality rates in young adults with diabetes mellitus (DM). Methods We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database for patients aged 15 to 44 years from 1999 to 2019 in the primary analysis. A secondary analysis included data from 2020 to 2022 to examine the effect of the COVID‐19 pandemic. We analysed patients in whom cardiovascular diseases (CVD) were listed as the main cause of death and DM as a contributing cause of death. In calculating age‐adjusted mortality rates (AAMR) per 100 000 individuals, we used CVD mortality in young adults with comorbid diabetes as the numerator and the overall population as the denominator. We determined temporal trends by estimating the average annual percent change (AAPC) using the Joinpoint regression program. Results Among 3 309 079 individuals aged 15–44 years who died, 30 978 deaths were due to CVD with comorbid DM listed as a contributing cause. The overall AAMR increased from 1.08 per 100 000 individuals in 1999 to 1.23 per 100 000 individuals in 2019, with an average APC of 0.75 (95% CI, 0.31–1.20). Compared with 1999, the percentage increase in CVD deaths in 2019 among young adults with comorbid DM was +6.2%, whereas a decrease of 19.9% was observed among those without comorbid DM. Males had a higher AAMR than females (1.60 vs. 0.97). Non‐Hispanic Black individuals and non‐Hispanic American Indian/Alaska Native individuals had the highest AAMRs of 2.99 and 2.89, respectively. The AAMR was higher in rural regions compared to urban areas (1.63 vs. 1.23). The overall AAMR increased markedly from 1.23 in 2019 to 1.60 in 2022, with a similar pattern observed across demographic subgroups. Conclusion Our study reveals a rising trend in CVD mortality in young adults with DM as a contributing cause. Males, non‐Hispanic Black individuals, and individuals from rural regions had higher AAMR than their counterparts. This warrants the development of specific healthcare policies aimed at these at‐risk populations. Lay summary Our study shows that cardiovascular disease (CVD) deaths are increasing in young adults with diabetes mellitus listed as a contributing cause.

Background: Studies in the past have demonstrated an association between sarcoidosis and pulmonary embolism (PE), but little is known about its impact, especially in young adults. We aim to determine the burden and impact of PE in young adults hospitalized with sarcoidosis. Methods: This study investigates the prevalence and consequences of PE in young adults aged 18–44 years hospitalized with sarcoidosis using data from the National Inpatient Sample (2016–2020) with relevant International Classification of Diseases (ICD)-10 codes. This study aims to address the primary outcomes of the burden and trends of PE and its associated impact on in-hospital mortality. Additionally, it explores secondary outcomes such as healthcare resource utilization and discharge patterns. Results: Among 50,385 young adults (median age 37 years) hospitalized with sarcoidosis, 1120 had PE, showing a linear increase from 2% in 2016 to 2.9% ( P < 0.001) in 2020. The sarcoidosis–PE+ group, predominantly in young blacks, exhibited a higher prevalence of comorbidities such as obesity, smoking, drug use, peripheral vascular disease, hypothyroidism and prior history of venous thrombus embolism. In contrast, the sarcoidosis–PE− group had a higher prevalence of diabetes (with/without chronic complication), hyperlipidemia and chronic pulmonary disease. Multivariable regression analysis adjusted for all potential sociodemographic and comorbid variables showed higher odds of all-cause mortality (odds ratio [OR]: 2.92, 95% confidence interval [CI]: 1.18–7.24, P < 0.02) in the sarcoidosis–PE+ group as compared to the sarcoidosis–PE− group. The sarcoidosis–PE+ group also had higher hospital costs and length of stay. Conclusion: The higher odds of in-hospital mortality with an increased length of stay and hospital cost observed in the sarcoidosis–PE+ group highlight the often underreported complications of sarcoidosis, particularly in a younger demographic. The relevance of this study stems from its potential to uncover trends that could lead to improved diagnostic and therapeutic strategies.

Abstract Study Objectives This study examined whether basal electromyographic (EMG) amplitude during sleep is altered in patients with isolated REM sleep behavior disorder (iRBD) and its relationship to disease progression, as well as changes across the sleep cycle. Methods Baseline polysomnograms collected from 95 iRBD patients (15 converters, 80 non-converters) and matched 24 controls were analyzed. EMG amplitude was calculated from submentalis recordings across all sleep stages using 3-s mini-epochs, with REM sleep further classified as REM sleep without atonia (RWA) and non-RWA (RA) according to the presence of “any” RWA events. Kaplan–Meier analysis assessed phenoconversion risk, and EMG amplitude was compared between early and late sleep cycles within each group. Results Group comparisons with post-hoc adjustment showed that EMG amplitude in RA and RWA was higher in non-converters than controls (adj-p &lt; .001), while converters showed further increases of EMG amplitude in N2 and N3 (adj-p &lt; .045). RA amplitude was higher in converters than non-converters (adj-p = .02). Increased EMG amplitude in N2, N3, and RA was associated with higher phenoconversion risk (p &lt; .05). EMG amplitude remained stable between early and late cycles during RA in both iRBD and controls. In contrast, iRBD patients showed a significant decrease in EMG amplitude during late cycles in N2 (p &lt; .009). Conclusions Elevated basal EMG amplitude during both REM and NREM sleep in iRBD patients shows potential as a prognostic marker, indicating muscle tone dysregulation beyond REM atonia loss and underscoring the need to consider broader sleep stages in iRBD evaluation. Statement of Significance This study provides compelling evidence that increased basal electromyographic amplitude during both REM and NREM sleep in isolated REM sleep behavior disorder (iRBD) patients serves as a marker of prodromal alpha-synucleinopathy. By showing that electromyographic abnormalities extend beyond discrete REM events to affect global muscle tone, our findings challenge the conventional view that iRBD pathophysiology is limited to REM-specific activity. Furthermore, the predictive value of these changes appears linked to muscle tone regulation across the sleep–wake cycle. These insights not only deepen our understanding of iRBD pathophysiology but also underscore the potential for refining diagnostic criteria.

Abstract Background Frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominant atrophy is an emerging area of interest. Recent findings by the International Working Group (IWG) have identified this subtype as having a distinct clinical profile within the FTD spectrum (Ulugut et al., 2024, A&D). However, its genetic and pathological underpinnings remain unexplored in large, multicultural cohorts. Methods Retrospective analyses encompassing clinical, genetic, pathological, and neuroimaging data from 23 IWG sites across 13 countries in Asia, Middle East, Europe, North and South America were conducted. The study included 444 patients with FTD exhibiting predominant RATL atrophy. Results Genetic screening was performed on 51% ( n = 225) of the cohort for at least the major frontotemporal lobar degeneration (FTLD) mutations including microtubule‐associated protein tau ( MAPT ), progranulin ( GRN ), and chromosome 9 open reading frame 72 ( C9orf72 ), or dementia panels encompassing extended sets of genes. Of these, 81% were sporadic, showing negative results for the screened genes and a modified Goldman Score of ≥ 3, indicating a negative family history for dementia. The MAPT mutation was the most common genetic variant, identified in 7% of the screened cases (Figure 1). Pathological confirmation was available for 63 patients. Among the sporadic cases, transactive response DNA‐binding protein 43 type C (TDP‐C) pathology was most prevalent (60%, n = 32), while tau‐MAPT pathology was most common in the genetic cases (38%, n = 16). Fifteen cases did not fit neatly into genetic or sporadic categories, displaying heterogeneous pathologies (Figure 2). At the initial visit, compared to genetic cases, patients with TDP‐C pathology were older, and more frequently exhibited semantic deficits, with less frequent attention difficulties and executive dysfunction. No differences were observed in sex distribution, symptom duration or disease severity between genetic and sporadic TDP‐C cases. However, left handedness was more common in TDP‐C cases (14%) compared to genetic cases (5%). Conclusion While FTD with RATL atrophy primarily appears sporadic, a significant proportion of cases exhibit genetic variants. These sporadic and genetic subtypes display distinct neuropathological features and clinical manifestations. Given the implications for therapeutic strategies, precise clinical and molecular subtyping is critical for enhancing patient management and ensuring appropriate enrollment in clinical trials.

Abstract Context Evidence on the evolution of cardiometabolic comorbidities following surgical remission of hypercortisolism is scarce. Objective To determine the impact of surgical remission on cardiometabolic comorbidities in patients with endogenous hypercortisolism and to identify factors associated with cardiometabolic improvement. Methods Prospective single-center cohort study (2019-2025) of adults with Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS) with surgical remission of hypercortisolism. Outcomes included (1) changes in severity of hypertension, diabetes mellitus (DM), hyperlipidemia, and obesity between baseline, 3, and 12 months postremission and (2) factors associated with improvement in comorbidities. Results Among 357 patients (49% MACS, 36% pituitary CS, 10% adrenal CS, 5% ectopic CS; median age 53 years [interquartile range 42-62]; 81% women), 336 (94%) had hypertension, 241 (68%) had obesity, and 122 (35%) had DM. At a median of 12 months postsurgery, improvement in hypertension occurred in 70% (90/128) of patients with CS and 51% (60/117) of patients with MACS, DM in 90% (46/51) patients with CS and 37% (13/35) patients with MACS, and obesity in 79% (77/97) patients with CS and 20% (14/71) patients with MACS. In a multivariable analysis, higher baseline biochemical severity scores were associated with improvement in hypertension [odds ratio (OR) 1.3, 95% confidence interval (CI) 1.1-1.5), DM (OR 2.5, 95% CI 1.7-4.1), and obesity (OR 1.5, 95% CI 1.2-1.8) at a median of 12 months postremission of hypercortisolism. Conclusion Postsurgical improvement of cardiometabolic comorbidities was observed in both patients with CS and MACS. Higher baseline biochemical severity scores were associated with higher postremission improvement in comorbidities.

Abstract Background Ten years after the original publication, the Centiloid framework is now broadly used to harmonize amyloid‐PET quantification, facilitate data sharing and comparison across cohorts, and even assist visual interpretation in clinical settings. We evaluated the global implementation of Centiloids by comparing their distribution and corresponding positivity thresholds across cohorts. Methods We gathered data from publicly available cohorts and reached out to investigators across the world to collect cross‐sectional Centiloids, demographic and clinical information, and visual read data. Gaussian mixture models (GMM, k=2) were fitted to Centiloid values for each cohort and cutoffs were calculated as mean + 2SD of the lower Gaussian. When visual reads were available, we determined Centiloid cutoffs that maximized correspondence with visual reads (Cohen’s kappa). Data was combined across cohorts using random effects meta‐analyses. Results As of January 2025, we included 37 cohorts ( n = 41,678 participants) with heterogeneous pipelines, radiotracers, and clinical and demographic characteristics (Table‐1). The low Gaussian peaks ranged from ‐9 to 10CL; the meta‐analysis identified a common peak at 1CL. The second peaks were more heterogeneous (range=38‐102CL; meta‐analysis outcome=64CL). Across cohorts, the proportion of cognitively unimpaired versus impaired participants impacted the position of both peaks, with better separation in cohorts enriched in impaired individuals (Figure‐1C). The meta‐analysis indicated a GMM‐based cutoff of 19CL (95%CI: 16‐21CL, Figure‐1B); subgroup analyses showed no evidence of significant effect between single versus multicenter settings (17 versus 20CL, p = 0.30), MRI‐based or PET‐only processing (18 versus 19CL, p = 0.88), and no evidence of difference across radiotracers (Flutemetamol: 16CL; PIB: 17CL, Flutafuranol: 18CL, Florbetaben: 19CL, Florbetapir: 20CL, p = 0.78). In a subset of 29,496 participants with visual reads available, binary visual reads corresponded well to Centiloids (common kappa=0.86, Figure‐2A). The visual read‐based cutoff of 24CL (95%CI: 21‐27CL, Figure‐2B) maximized correspondence between visual read and quantification and was slightly higher than the GMM‐based cutoff. All meta‐analysis models showed high non‐random heterogeneity (I 2 >80%) across studies, suggesting non‐random differences in peaks and cutoffs. Conclusions Meta‐analysis‐based cutoffs align well with thresholds from the existing literature. High heterogeneity among studies underscores the need to investigate contributing factors, raising concerns about applying common cutoffs.

Background: Patients with abdominal aortic aneurysms (AAA) often have comorbidities that make them poor candidates for open surgical repair (OSR). Endovascular aortic aneurysm repair (EVAR) circumvents the morbidity associated with OSR of AAA. Candidacy for EVAR is impacted by multiple factors, including the quality and size of vascular access vessels and involvement of visceral arteries, as seen in paravisceral abdominal aortic aneurysms (PVAAA). Additional challenges, such as obesity, can complicate vascular access during EVAR. PVAAA may be better suited for fenestrated EVAR (FEVAR) using a physician-modified endograft (PMEG). Materials and Methods: In this report, we describe the case of a 64-year-old female patient with a complex PVAAA in the setting of significant aortoiliac occlusive disease (AIOD) with intermittent claudication. We describe a successful staged FEVAR technique in which vascular access challenges were first addressed by recanalization of the iliac system with femoral conduit (FC) creation, followed by successful FEVAR using bilateral FC for deployment of the PMEG. Conclusion: Patients with PAAA have unique and complex pathology that are clinically challenging to address. It is not uncommon that these patients also have co-morbid conditions that make them less-than ideal candidates for open repair. Patients may also have other conditions such as AIOD which make EVAR complex. Staged approach with iliac recanalization and femoral conduit creation followed by FEVAR with PMEG is an effective treatment option for high-risk complex patients and can help avoid common complications such as groin infection and delay in FEVAR which may result in a catastrophic event such as interval AAA rupture.

Abstract Osteonecrosis (ON) of the femoral head is a significant complication following chronic corticosteroid treatment, especially in adolescents and young adults. While studies in the adult population suggest that early core decompression augmented with bone marrow aspirate concentrate injection (BMAC) may reduce progression, evidence in younger patients remains scarce. This study evaluates survivorship free from femoral head collapse and conversion to total hip arthroplasty following core decompression with BMAC in patients under 25 years old with corticosteroid-induced femoral head ON. A retrospective review was conducted of 13 patients (24 hips) who underwent hip core decompression with BMAC for corticosteroid-induced femoral head ON. Variables analyzed included sex, body-mass index, age at index surgery, continued corticosteroid use, concomitant labral tear, Kerboul angle/grade, and Steinberg classification of osteonecrosis. These variables were assessed for their association with survivorship free of THA, conversion to THA, and patient reported outcomes (PROs) (modified Harris Hip Score [mHHS] and Hip Disability and Osteoarthritis Outcome Score [HOOS-12]). The mean follow-up duration was 10 ± 5.4 years. At the final follow-up, 11 hips (45.8%) required reoperation, including 10 total hip arthroplasties and one femoral head resurfacing. Progression to radiographic femoral head collapse occurred in 9 hips (37.5%), resulting in a collapse-free survival rate of 62.5%. The mean survival time until reoperation was 8.34 years. Continued corticosteroid use (p=0.033), Steinberg stage &gt;2 (p=0.044), male sex (p=0.045), and high BMI (p=0.002) were associated with increased risk for reoperation. On multivariate analysis, ongoing corticosteroid use (OR=6.4, p=0.01) and Steinberg stage &gt;2 (OR=4.3, p=0.04) were predictors of reoperation. Patient-reported outcomes at final follow-up included a mean mHHS of 77.5 and a HOOS-12 score of 80%. Core decompression with BMAC for corticosteroid induced femoral head ON in adolescents and young adults resulted in collapse-free survival rate of 62.5% at average 10 years follow up with an average reoperation-free survival of 8.34 years. Patients with Steinberg stage ≥2 and ongoing corticosteroid use had high rates of reoperation and conversion to total hip arthroplasty. Our data highlights that careful patient selection and shared decision-making remain critical in optimizing patient outcomes in this challenging patient population.

Background Level I trauma centers employ various orthopaedic call strategies based on resources and surgeon subspeciality availability. Objective We hypothesize when surgeons fellowship trained in trauma are solely on call that patient outcomes will be improved compared to a combined plan. Methods Retrospective cohort study from two 24-month time periods at an academic level one trauma center. The first cohort consisted of only trauma surgeons taking call. The second cohort consisted of a combination of trauma and other subspecialities taking call. The primary outcome analyzed was time from admission to operating room for hip, femoral shaft, distal femur, tibia shaft, pelvic ring and acetabulum fractures. Secondary outcomes analyzed included length of stay, 90 day incidence of reoperation, mortality, VTE and readmission. Results Eight hundred and fifty seven patients in the trauma cohort and 992 patients in the combined cohort met the inclusion criteria. The time from admission to index surgical procedure was significantly shorter in the trauma cohort (1.7 vs 2.4). Length of stay (8.95 vs 11 days) and 90 day mortality (1.8% vs 3.8%) was improved in the trauma cohort. There was no difference in 90 day rate of VTE, readmission or reoperation. Length of stay and time to OR in pelvic ring injuries and acetabulum fractures were doubled compared to the hybrid group. Conclusions Our findings suggest that when trauma fellowship trained surgeons are the only ones taking call patients have a shorter time from admission to index surgical procedure, length of stay and lower mortality rate.

Abstract Objective Evidence on the duration of post-operative adrenal insufficiency (AI) in patients with endogenous hypercortisolism is scarce. We sought to determine the duration of post-operative AI and to identify factors associated with the duration of AI in patients undergoing surgery for endogenous hypercortisolism. Methods We conducted a single-center prospective cohort study, 2019-2025, of patients with endogenous hypercortisolism [Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS)] treated with surgery. Associations of demographics, body mass index (BMI), clinical, and biochemical hypercortisolism severity, subtype of hypercortisolism, pre-surgical hypercortisolism duration, glucocorticoid type, and nadir cortisol in relation to duration of AI were investigated. Results The 242 patients [41% MACS, 46% pituitary CS, 12% adrenal CS, 1% ectopic CS, median age 50 years (IQR: 40-60), 85% women] who developed postsurgical AI were followed for a median duration of 13.7 months (IQR 7.2-26.3). The median time to recovery of AI was shorter in MACS vs. overt CS (3.9 months (95% CI: 3.3-6.2) vs. 13.5 months (95% CI 11.3-18.3), P value &lt; .001). On multivariable analysis adjusting for age, sex, BMI, and glucocorticoid type, moderate to severe biochemical severity score (β = 11, P value &lt; .001) and moderate to severe clinical severity score (β=8.7, P &lt; .001), were associated with a longer duration of AI. Conclusions Baseline clinical and biochemical hypercortisolism severity scores may inform individualized counseling on post-operative AI duration in patients treated for CS and MACS.