Citations

Abstract Context Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes and obesity and can lead to substantial weight loss. In patients taking levothyroxine, weight loss can reduce thyroid hormone requirements and potentially associated adverse effects. Thyroid-stimulating hormone (TSH) monitoring is essential but unclear whether thyroid function is routinely reassessed after GLP-1 RAs initiation. Objective Examine the changes in the timing of TSH testing after GLP-1 RAs. Design Retrospective cohort study emulating a target trial using Medicare from January 1, 2011, to December 31, 2020. The primary analysis followed an intention-to-treat approach. Patients were matched 1:1 using propensity scores. Logistic regression models and informed by least absolute shrinkage operator variable selection were used. Setting The 15% sample of U.S. Medicare fee-for-service claims data. Patients or Other Participants Adults aged ≥65 years with type 2 diabetes on a stable levothyroxine dose at baseline. Intervention(s) Initiation of GLP-1 RAs vs initiation/ongoing use of sodium-glucose cotransporter-2 inhibitors (SGLT-2is). Main Outcome Measure(s) TSH testing during follow-up. Results Among 5370 matched patients, the mean age was 73.2 years. 71.6% were women, and 87.1% were White. Approximately 83.0% of patients in both treatment groups receive a TSH testing within a 1-year follow-up. The mean time to TSH testing was approximately 130.5 days for both groups. Conclusion TSH testing patterns did not differ between GLP-1 RAs and SGLT-2is, despite the greater likelihood of requiring levothyroxine dose adjustment associated with weight loss seen with GLP-1 RA therapy. Given levothyroxine's widespread use, this gap suggests missed opportunities for timely and weight-responsive thyroid monitoring.

Abstract Aims Obesity is linked with worse outcomes in hypertrophic cardiomyopathy (HCM). While both bariatric surgery (BS) and GLP-1 receptor agonists (GLP-1RA) promote weight loss and may improve cardiometabolic risk, their comparative outcomes in HCM remain unclear. Methods and results Adults with HCM and body mass index (BMI) ≥ 30 kg/m were divided into two cohorts: (i) GLP-1 RA users who never had BS, and (ii) BS patients who never received GLP-1 RA. Propensity score matching (1:1) was performed to balance demographics, comorbidities, and medications. Outcomes over 24 months include all-cause mortality, acute heart failure (HF) hospitalization, arrhythmias, change in BMI, and cardiovascular symptoms. Hazard ratios with 95% confidence intervals were estimated using Cox models. Of 5002 patients, 955 were included in each matched cohort after matching (mean age 54 ± 13 years, 70% female, BMI 40.0 kg/m). GLP-1 RA was associated with a significantly lower observed rate of all-cause mortality compared with BS (2.0% vs. 4.4%; HR 0.46; 95% CI 0.27–0.80; P = 0.004) and HF hospitalization (8.7% vs. 14.0%; HR 0.60; 95% CI 0.46–0.79; P < 0.001). Similarly, GLP-1 RA use was associated with a lower incidence of composite cardiovascular outcomes (10.7% vs. 17.2%; HR 0.60; 95% CI 0.47–0.77; P < 0.001). Rates of arrhythmia and cardiovascular symptoms were comparable between the two groups. BMI reduction was greater after bariatric surgery (−4.0 vs. −2.6 kg/m; P < 0.001). Conclusion In obese patients with HCM, GLP-1 RA therapy was associated with lower all-cause mortality and fewer HF events compared with BS. Future studies are warranted to confirm our findings.

Objective: Battlefield acupuncture (BFA) has gained widespread clinical use for patients presenting to emergency departments (EDs). This systematic review of randomized controlled trials (RCTs) aims to assess the efficacy and safety of BFA in ED settings. Methods: A literature search was conducted in OVID and Scopus databases for RCTs involving BFA applied in ED settings. The risk of bias was evaluated using the Cochrane Collaboration risk of bias tool, while the methodological quality of RCTs was assessed using the Jadad score. Due to the heterogeneity of the included studies, a qualitative analysis was performed. Results: Seven studies involving 758 patients met the eligibility criteria. Among these, five studies evaluated traditional BFA in conjunction with standard analgesia care, while two studies assessed modified BFA alongside standard care. Most of the included studies were found to have a high risk of bias, leading to an overall classification of low quality according to the Jadad criteria. A descriptive analysis was performed due to heterogeneity in the interventions, observational timepoints, and outcomes reported in the included studies. Positive results were demonstrated in 71% of the studies. The most common conditions documented as the primary ED presentation included back pain, acute abdominal pain, lower extremity pain, neck pain, and acute sore throat. Notably, no severe adverse events were reported. Conclusion: BFA may offer a safe adjunct to standard care for pain management in ED settings. However, the limited methodological rigor and small number of existing RCTs reduce confidence in the current evidence. Well-designed, robust studies are needed to clarify their effectiveness and support stronger clinical recommendations.

Abstract Reported prevalence estimates of Lewy body pathology (LBP) vary widely, often without considering brain regional distributions or demographic influences. Large, population-representative autopsy cohorts are needed to provide estimates and clarify the distribution and clinical implications of LBP. Neuropathological, genetic, and clinical data were pooled from nine community- or population-based brain autopsy cohorts in the USA (n=6), Brazil, Austria, and Finland (n=7309 total; 59% women; mean age of death 84.2 years). Cognitive status was available for 6166 participants: dementia (38.5%), mild cognitive impairment (14.8%), and cognitively unimpaired (47.0%). Frequency of LBP was examined by anatomical distribution (neocortical, limbic, brainstem, amygdala, olfactory) and stratified by covariates. Prevalence was calculated in meta-analysis, and mixed-effect logistic regression examined associations with sex, cognitive status, Alzheimer’s disease neuropathological change (ADNC), and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) co-pathology. Overall, 27.3% of participants had LBP: neocortical 8.4%, limbic 6.8%, brainstem 4.8%, amygdala 3.7%, and olfactory 3.6%. Neocortical LBP was associated with dementia (present in 15%; OR=4.06 [95%CI 3.24-5.10]) and with increased odds of ADNC (OR=2.30 [95%CI 1.88–2.81]) and LATE-NC (OR=2.03 [95%CI 1.69-2.44]). Sex differences were not observed in the frequencies of neocortical or limbic LBP. However, amygdala-predominant LBP was more frequent in women (OR=1.53 [95%CI 1.06-2.21]) whereas brainstem-predominant LBP was more common in men (OR=0.64 [95%CI 0.49-0.84]). Additionally, amygdala-predominant LBP was associated with increased odds of comorbid ADNC (OR=12.7 [95%CI 5.30–30.6]) while brainstem-predominant LBP was not associated with greater odds of ADNC co-pathology (OR=0.88 [95%CI 0.67–1.16]). Pooling data from large, international community-based autopsy cohorts allows for more robust estimates of region-specific LBP prevalence and their associations with cognitive status. The observed sex- and co-pathology–specific differences in brainstem and amygdala-predominant LBP highlight potential biological heterogeneity and suggest that distinct disease pathways may underlie these patterns.

Abstract Aims The clinical significance of early recurrences during the blanking period following pulmonary vein isolation (PVI) remains uncertain, particularly after pulsed field ablation (PFA). This study aimed to evaluate the prognostic impact of early recurrences at 30-, 60-, and 90-day thresholds on outcomes following PFA for atrial fibrillation (AF). Methods and results Consecutive patients who underwent PFA for AF across multiple centres within the Mayo Clinic health system were included. The primary endpoint was AF-free survival. Kaplan–Meier and multivariate Cox regression analyses were performed to compare outcomes between patients with and without early recurrences using 30-, 60-, and 90-day thresholds. A total of 1162 patients were included. The estimated AF-free survival at 1 year was 70%. Early recurrences within 30-, 60-, and 90-days post-ablation were significantly associated with late recurrences beyond 90 days (hazard ratio [HR] 5.9, 95% confidence interval [CI] 4.4–7.9, P < 0.01; HR 6.6, 95% CI: 5.0–8.6, P < 0.01; and HR 9.1, 95% CI: 7.0–11.7, P < 0.01, respectively). These findings remained significant among patients undergoing continuous rhythm monitoring. Early recurrences within 30 days in this subgroup were significantly associated with a 1-year AF burden >1% or the need for repeat AF ablation (odds ratio 25.0, 95% CI: 6.6–126.8, P < 0.01). Conclusion Early recurrences following PFA are strongly predictive of long-term arrhythmia recurrence and are unlikely to represent transient inflammatory phenomena. Accordingly, the applicability of the conventional blanking interval after PFA should be reconsidered.

Summary Evidence for an association between insulin‐like growth factors (IGF) and multiple myeloma (MM) is inconsistent. We examined total IGF‐I concentrations and risk of MM by combining baseline serological data among UK Biobank participants ( n = 444 187; 732 incident MM) with a two‐sample Mendelian randomisation (MR) analysis using identified genetic variants associated with circulating total IGF‐I and IGF‐binding protein 3 (IGFBP‐3) in the InterLymph consortium (2434 MM and their 2567 controls). Finally, additional lymphoid neoplasm (LN) subtypes were included for comparison with the main hypothesis. Circulating IGF‐I level was positively associated with MM risk Hazard ratio‐HR‐per one standard deviation‐SD‐increase (HR 1‐SD = 1.11, 95% confidence interval [CI]: 1.01–1.22; p ‐value = 0.03), especially closer to diagnosis. Genetically inferred IGF‐I levels were associated with increased MM risk (odds ratio [OR] = 1.27, 95% CI: 1.05–1.54) but not with any other LNs. Genetically inferred IGFBP‐3 levels showed no associations with any LN evaluated. Corroborating previous findings, in a secondary analysis, IGF‐I levels were associated with the risk of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) in males with higher body mass index (HR 1‐SD in obese male = 1.36, 95% CI: 1.14–1.61). Our serological and MR analyses suggest a contributing role of IGF‐I in the susceptibility of MM; the CLL/SLL findings warrant further investigation considering sex‐specific adiposity.

Background. Liver transplant recipients face high risks of cardiometabolic events after transplant, driven by posttransplant weight gain, diabetes, hypertension, as well as immunosuppression-related side effects. Glucagon-like peptide-1 receptor agonists (GLP1RAs) improve metabolic and cardiorenal outcomes in nontransplant populations, but their role in liver transplant recipients remains understudied. Methods. This retrospective cohort study used TriNetX data (January 2010–December 2023) to compare outcomes in liver transplant recipients prescribed GLP1RAs (semaglutide, dulaglutide, liraglutide) within 1-mo posttransplant (n = 546) versus nonusers (n = 37 153). Propensity score matching (1:1) balanced demographics, comorbidities, and medications (n = 541 per group). Outcomes included mortality, hospitalizations, cardiovascular/renal/respiratory events, and graft outcomes. Results. Over a mean follow-up 838.5 d (SD 291.9) in the GLP1RA cohort and 884.3 d (SD 313.7) in the non-GLP1RA group, GLP1RA use was associated with a 43% lower all-cause mortality (7.0% versus 12.9%; hazard ratio [HR], 0.566; 95% confidence interval [CI], 0.381-0.841) and 39% fewer hospitalizations (60.4% versus 74.5%; HR, 0.613; 95% CI, 0.530-0.710). Acute heart failure (HR, 0.386; 95% CI, 0.285-0.524), renal failure/dialysis (HR, 0.489; 95% CI, 0.413-0.579), and respiratory failure (HR, 0.484; 95% CI, 354-0.662) risks were significantly reduced. No differences were observed in graft failure/rejection, myocardial infarction, stroke, atrial fibrillation/flutter, ventricular tachycardia, or ischemic optic neuropathy. Conclusions. Early GLP1RA initiation in liver transplant recipients was associated with reduced mortality, hospitalizations, respiratory, and cardiorenal complications without compromising graft safety. These findings support GLP1RAs as a promising adjunct therapy, warranting prospective trials to confirm benefits in this high-risk population.

Abstract INTRODUCTION The infectious hypothesis suggests that microbes like herpesviruses may play a role in the pathogenesis of Alzheimer's disease (AD) and other related dementias through methods that may include viral genome integration. The occurrence of herpesvirus genome integration in dementia patients has not been thoroughly characterized. METHODS Over 7500 total whole‐genome sequences from control, frontotemporal dementia/amyotrophic lateral sclerosis spectrum, Lewy body dementia (LBD), multiple system atrophy (MSA), and AD cohorts were screened for the integration of pathogen genomes using the PathSeq computational tool. RESULTS Low PathSeq scores for human herpesvirus 6 (HHV‐6) were consistent with the suspected integration of viral genome segments. The LBD and MSA cohorts had a significantly higher prevalence of this partial HHV‐6 genome integration. DISCUSSION This higher prevalence in both synucleinopathies was not noted in other herpesviruses, suggesting that the integration of HHV‐6 may play a role in a subset of these patients. Highlights Over 7500 whole‐genome sequences from controls and dementia patients were analyzed. Sequences consistent with integrated herpesviruses were identified using PathSeq. Prevalence of partial HHV‐6 integration was higher in synucleinopathies. Herpesviruses genome integration may play a role in subsets of dementia patients.

Abstract Purpose Although the Woven EndoBridge (WEB) device is increasingly used for the treatment of wide-neck intracranial aneurysms, including in the acute rupture setting, comparative evidence assessing the impact of rupture status remains limited. This study compared angiographic, safety, and clinical outcomes between ruptured and unruptured intracranial aneurysms treated with WEB. Methods We conducted a retrospective analysis of prospectively collected data from the multicenter cohort registry WorldWideWEB, including consecutive adult patients with intracranial aneurysms treated with the WEB. Patients were stratified into groups of ruptured and unruptured aneurysms. Propensity score matching was used to balance baseline characteristics between both groups. Retreatment rate was the primary outcome. Secondary outcomes included mRS, safety events (thromboembolic complications) and angiographic outcomes (periprocedurally and last follow-up). Results Among 1,220 patients, 342 (28.0%) presented with ruptured aneurysms. There was no significant difference in the rate of thromboembolic complications between groups (11.8% vs 5.9%, p = 0.056). At follow-up, adequate occlusion was lower (82.2% vs 93.3%, p < 0.002) and functional outcomes were worse (mRS ≥2 in 34.1% vs 21.9%, p = 0.012) among patients with ruptured aneurysms. Periprocedural adequate occlusion (53.3% vs 53.8%, p>0.9) and retreatment rates (11.8% vs 7.1%, p = 0.14) did not differ between groups after matching. Conclusion Ruptured aneurysms demonstrated expected inferior follow-up functional and angiographic outcomes when compared with unruptured aneurysms, but no difference in retreatment rate and procedural safety. These findings support WEB as a safe and effective treatment option for appropriately selected ruptured intracranial aneurysms in routine clinical practice.