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Importance Monoclonal gammopathy of undetermined significance (MGUS) is associated with an increased risk of cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have demonstrated cardiorenal benefits in patients with type 2 diabetes, but their effectiveness in patients with MGUS remains unexplored. Objective To assess the effectiveness of GLP-1 RAs for primary prevention of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with MGUS and diabetes. Design, Setting, and Participants This retrospective cohort study used a propensity score–matched analysis of data from the TriNetX Global Database, encompassing patients diagnosed with diabetes and MGUS between January 1, 2018, and January 13, 2023. Patients with prior heart failure (HF), ischemic heart disease, coronary revascularization, or stroke or transient ischemic attack before MGUS diagnosis were excluded. The cohort was divided into 2 groups: GLP-1 RA users and nonusers at baseline. After 1:1 propensity score matching, GLP-1 RA users and nonusers were compared up to 5 years from the MGUS diagnosis date. Data analyses were completed January 19, 2025. Exposure GLP-1 RA use within 1 year before MGUS diagnosis. Main Outcomes and Measures The primary end point was MACCE, defined as a composite of all-cause mortality, new-onset HF, acute coronary syndrome, and stroke or transient ischemic attack. Secondary end points included individual MACCE components, decompensated HF, and acute kidney injury or end-stage kidney disease. Results A total of 4871 patients with MGUS (mean [SD] age, 68.9 [10.1] years; 2366 [48.5%] male) were included (473 GLP-1 RA users and 4398 non-users). A total of 460 users were matched to 460 nonusers, with balanced characteristics (mean [SD] age, 65.0 [10.6] vs 65.1 [11.0] years; 229 [49.7%] male vs 234 [50.8%] male), including 14 patients (3.0%) vs 13 patients (2.8%) identifying as Asian, 8 (21.3%) vs 92 (20.0%) as Black or African American, 25 patients (5.4%) vs 20 patients (4.3%) as Hispanic or Latino, and 243 patients (52.8%) vs 250 patients (54.3%) as White. GLP-1 RA use was associated with a significantly lower risk of MACCE (hazard ratio [HR], 0.75; 95% CI, 0.60-0.93). Significant reductions were also observed in all-cause mortality (HR, 0.57; 95% CI, 0.37-0.87), new-onset HF (HR, 0.69; 95% CI, 0.54-0.90), decompensated HF (HR, 0.60; 95% CI, 0.43-0.84), and acute kidney injury or end-stage kidney disease (HR, 0.73; 95% CI, 0.57-0.92). Conclusions and Relevance The findings of this cohort study of GLP-1 RA use vs no use in patients with MGUS and diabetes suggest the potential of GLP-1 RA for primary prevention of MACCE. These findings warrant further investigation in prospective randomized trials.

Abstract Background Medical chaperones are authorized individuals present during physical examinations involving the genitals, breasts/chest, or anal areas. The use of medical chaperones may provide an opportunity to improve transgender and gender diverse (TGD) patients’ experiences with sensitive examinations. Aim To examine TGD adult patients’ preferences and comfort for having a medical chaperone and whether TGD-specific characteristics, social anxiety symptoms, and feelings of medical mistrust are associated with preference for having a medical chaperone present during a sensitive physical examination. Methods This study used a cross-sectional survey that randomly sampled adult patients from a gender clinic in the Midwest region of the U.S. A total of 420 surveys were mailed. Sixty-two surveys were returned undeliverable, 358 reached recipients; 151 were returned (42.1% response rate). The survey included items related to demographics, gender-related anatomical dysphoria, social anxiety symptoms, feelings of medical mistrust, and preference and comfort towards medical chaperones. Results Among 149 respondents, 74 (49.7%) reported comfort for the idea of having a medical chaperone present during a sensitive physical examination, 50 (33.6%) reported neutral comfort, and 25 (16.8%) reported discomfort. Among 147 respondents, 89 (60.5%) endorsed a preference for a female medical chaperone. We found no associations between gender-related anatomical dysphoria or social anxiety symptoms and comfort for having a medical chaperone, or the gender preference for a medical chaperone. Medical mistrust was associated with lower comfort with having a medical chaperone present during a sensitive physical examination. Clinical Implications Routinely offering medical chaperones, especially female chaperones, is like to be generally acceptable to most TGD patients. These findings may inform clinic policies on providing medical chaperones during sensitive examinations. Strengths and Limitations This study is the first to examine TGD preferences for medical chaperones. Findings are limited by a single site, homogeneous sample, cross-sectional design, and reliance on hypothetical rather than observed examinations. Conclusion TGD adults report comfort with the concept of having a medical chaperone during sensitive examinations and most would prefer the chaperone to be female. Preference for having a medical chaperone present during a sensitive physical exam is not likely influenced by gender dysphoria or social anxiety.

OBJECTIVE The aim of this study was to evaluate mortality and progression outcomes in patients undergoing stereotactic radiosurgery (SRS) for breast cancer brain metastases and to identify associated risk factors using a national quality registry. METHODS The NeuroPoint Alliance (NPA) SRS Registry was employed for this study, which conducted prospective enrollment of patients undergoing SRS at 16 participating centers from 2017 to 2024. Outcomes of interest included the post-SRS EQ-5D score change, overall survival, local progression, out-of-field progression, and overall intracranial progression. For all time-to-event analyses, Kaplan-Meier curves and multivariable Cox regressions with hazard ratios were used. RESULTS A total of 138 patients (127 female, mean age 59.8 years) were identified; 46.4% had a single lesion, 42.0% had 2–4 lesions, and 11.6% had ≥ 5 lesions, while 87.0% had a Karnofsky Performance Status (KPS) score between 80 and 100. The median overall survival was 17.9 months, and independent predictors of all-cause mortality included a KPS score ≤ 90 (HR 6.73) and diabetes mellitus (HR 3.35). The median time to local progression was 19.8 months. More than 5 lesions at baseline (HR 9.03) and a marginal dose ≤ 17.6 Gy (HR 8.00) were predictive of local recurrence. The median was not reached for out-of-field progression, and predictors included ≥ 2 lesions at the time of SRS (HR 3.20) and a marginal dose ≤ 17.6 Gy (HR 4.61). At the final follow-up assessment, 17.1% of patients experienced no change according to the EQ-5D, while 34.3% had improvement, 11.4% had mixed results, and 37.1% had worsened health. In the multivariable linear regression model, pre-SRS resection (r = 1.92) and baseline EQ-5D score (r = 1.29) were statistically significant predictors of quality of life at the final follow-up assessment. CONCLUSIONS Using real-world data from the NPA SRS Registry, this study demonstrated comparable outcomes in patients who underwent SRS for breast cancer brain metastases compared with those of previous literature. The number of lesions at the time of SRS and the marginal dose were independent risk factors for local recurrence, out-of-field progression, and overall intracranial progression. Pre-SRS resection and baseline EQ-5D score were independent predictors of quality of life following SRS.

We investigated the prognostic impact of blast counts, TP53 allelic state determinants (number of hits, del(17p), variant allele frequency, complex karyotype),and a novel karyotypic clonal cell fraction (≤50% clonal cells vs >50% clonal cells (termed ‘CK50’)) in 495 individuals with TP53- mutated ( TP53 MUT ) myeloid neoplasms. Outcome examined was 24-month survival (OS24). The cohort (median age 71) included 29% (144/495) myelodysplastic syndromes (MDS)/MDS-acute myeloid leukaemia (AML) (1%–19% blasts) and 71% (351/495) AML (≥20% blasts), with 18% (81/460) having low CK50. Overall, 83% received front-line hypomethylating agents. Higher blast counts (<20% vs ≥20%) were marginally associated with CK50 (p=0.08). In the OS24 analysis, blast count showed a marginal association with OS24 (HR 1.3 (95% CI 1.0 to 1.6); p=0.07), while CK50 predicted significantly inferior outcomes (HR=1.7 (95% CI 1.2 to 2.3); p=0.002). In a multivariable model including all TP53 allelic state determinants, only CK50 and complex karyotype remained relevant for predicting adverse outcomes.

INTRODUCTION: Many patients with chronic pouchitis and Crohn's-like disease of the pouch (CLDP) are treated with biologics; however, the comparative effectiveness of advanced therapies in this population has not been systematically evaluated. We sought to compare the effectiveness of antitumor necrosis factor α (anti-TNF) therapies and ustekinumab in patients with chronic inflammatory conditions of the pouch. METHODS: We conducted a prospective, multicenter, cohort study. We included patients with chronic pouchitis and CLDP initiating treatment with anti-TNF therapies or ustekinumab. The primary outcome was clinical remission at 6 months after induction. We also evaluated clinical remission at 6 months among patients with chronic pouchitis and CLDP separately. RESULTS: Among 132 patients, 106 (80%) had a diagnosis of CLDP and 82 (62%) initiated therapy with ustekinumab. A significantly higher proportion of patients with CLDP treated with ustekinumab were in clinical remission at 6 months as compared with patients treated with anti-TNF therapy (62% vs 40%, P = 0.027); however, there was no significant difference among patients with chronic pouchitis ( P = 0.946). There was no independent statistical significance in the odds of remission at 6 months among patients with CLDP among patients receiving ustekinumab compared with anti-TNF therapy (adjusted odds ratio 1.91, 95% confidence interval 0.69–5.30) after adjusting for presence of a fistula, number of preoperative advanced therapies, and number of advanced therapies after IPAA. DISCUSSION: These data suggest the potential benefit of ustekinumab in patients with CLDP and should prompt future novel effectiveness evaluations in this population.

OBJECTIVE In many individuals, type 2 diabetes (T2D) remains poorly controlled despite taking multiple glucose-lowering therapies. Several studies have demonstrated that endogenous hypercortisolism is prevalent among these individuals. We tested whether cortisol-directed therapy improves their glycemic control. RESEARCH DESIGN AND METHODS In this prospective, multicenter, double-blind study, 136 individuals with T2D (hemoglobin A1c [HbA1c] 7.5%–11.5% [58–102 mmol/mol] on multiple medications) and hypercortisolism (by dexamethasone suppression test) were randomized 2:1 to the glucocorticoid receptor antagonist mifepristone (300–900 mg once daily; n = 91) or placebo (n = 45) for 24 weeks, with stratification by presence/absence of an adrenal imaging abnormality. The primary end point was the change in HbA1c. Secondary end points included changes in glucose-lowering medications, weight, and waist circumference and safety. RESULTS Mean baseline HbA1c in the study cohort was 8.55% (69.9 mmol/mol). At 24 weeks, the least squares mean (LSM) difference from placebo in HbA1c was −1.32% (95% CI −1.81 to −0.83; P &lt; 0.001). Participants receiving mifepristone experienced reductions in body weight and waist circumference (placebo-adjusted LSM differences of −5.12 kg [95% CI −8.20 to −2.03] and −5.1 cm [−8.23 to −1.99], respectively). Of participants on mifepristone, 46% discontinued therapy, compared with 18% on placebo. Adverse events with mifepristone (&gt;10% of participants) included hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness, consistent with mifepristone’s known tolerability profile. Increases in blood pressure also occurred. CONCLUSIONS In individuals with inadequately controlled T2D and hypercortisolism, cortisol-directed medical therapy with mifepristone reduced HbA1c, with a manageable tolerability profile.

Objective: We comparatively analyzed the longitudinal outcomes of conversion to open procedure, laparoscopic subtotal cholecystectomy (CCY), and laparoscopic cholecystostomy tube placement. Background: Severe cholecystitis often causes dense inflammation that distorts the hepatocystic anatomy and can make safe dissection during CCY challenging. However, controversy exists regarding the optimal bailout procedure in such situations. Methods: The New York and Florida State all-claims databases were queried for patients who underwent laparoscopic CCY for acute cholecystitis from 2012 to 2021. Hierarchical logistic regression models were used to obtain adjusted estimates, with fixed effects assigned to patient-level variables and random effects assigned to hospital identifiers to adjust for intraclass correlation. Results: Of 384,948 laparoscopic CCYs performed, 5448 (1.4%) were not completed laparoscopically; 1370 underwent conversion to open procedure, 2646 underwent laparoscopic subtotal CCY, and 1432 underwent laparoscopic cholecystostomy tube placement. The conversion to open rate decreased from 0.6% in 2012 to 0.3% in 2021, while the laparoscopic subtotal CCY rate increased from 0.2% in 2012 to 1.4% in 2021. The 1-year bile duct injury (BDI) rate was highest for the conversion to open group (4.4%), followed by the laparoscopic subtotal CCY (0.8%) and laparoscopic cholecystostomy tube groups (0.3%, P<0.001). On adjusted analyses with the conversion to open group as the control, laparoscopic subtotal CCY (OR: 0.17, P<0.001) and laparoscopic cholecystostomy tube were associated with lower BDI rates (OR: 0.08, P<0.001, Figure). The 1-year postoperative endoscopic biliary intervention rate was lowest for the conversion to open group (4.2%), followed by the laparoscopic subtotal CCY (8.4%) and the laparoscopic cholecystostomy tube groups (8.8%, P<0.001). The completion CCY rates for the laparoscopic subtotal CCY and laparoscopic cholecystostomy tube groups were 2.1% and 23.4%, respectively. Among completion CCYs, the open rates were 56.4% in the laparoscopic subtotal CCY group versus 24.5% in the laparoscopic cholecystostomy tube group (P<0.001). Conclusions: In patients with severe cholecystitis requiring a bailout procedure, the BDI rate was highest after conversion to open procedure. Laparoscopic subtotal CCY and laparoscopic cholecystostomy tube were associated with lower BDI rates at the cost of higher postoperative endoscopic biliary intervention rates. Completion CCYs were required in 2.1% and 23.4% of patients who underwent laparoscopic subtotal CCY and laparoscopic cholecystostomy tube placement, respectively, of which the former group’s CCY was more likely to require an open operation.