Searched for: department:Medicine. General Internal Medicine
recentyears:2
school:SOM
Somatostatin 5 receptor expression in prolactinomas: Is there a role for Pasireotide in the management of prolactinomas?
Agrawal, Nidhi; Mehta, Sonal; Feelders, Richard A; Skwiersky, Samara; Campana, Claudia; Dogan, Fadime; van Koetsveld, Peter M; Neggers, Sebastian J C M M; Wright, Kyla; Kim, Hyon; Zagzag, David; Hofland, Leo J
The majority of prolactinomas are treated with dopamine agonists (DA) with excellent response, however DA-resistance occurs in 10% of prolactinomas. Somatostatin (SST) receptors have been increasingly studied in prolactinomas. There are five SST receptor subtypes and a significant number of prolactinomas show expression of SST5 and SST1 mRNA. The somatostatin analog (SSA) pasireotide, which has 40-fold greater binding affinity to SST5 compared to first-generation SSAs, shows promising results in case reports of DA-resistant prolactinomas. This two-center retrospective cohort study investigated the expression patterns of dopamine 2 (D2R), SST2 and SST5 receptors in surgical specimen of 34 patients with prolactinomas, 22 of which were DA-resistant. In vitro effects of cabergoline, octreotide and pasireotide on prolactin production was also examined in cultured prolactinoma cells. Receptor expression was scored using the immunoreactivity score (IRS). 31/34(91%) patients used DA preoperatively; 22/34(64.7%) were DA-resistant. Receptor expression in the cases was 97.1% for D2R, 70.6% for SST5 and 41.2% for SST2. In the majority of SST2 positive cases SST2 expression was very low. In in vitro studies comparing the effects of octreotide, pasireotide, and cabergoline on prolactin secretion, octreotide was the least potent drug and cabergoline was the most potent. SST5 and D2R expression was highest in prolactinomas showing the highest response to pasireotide and cabergoline in vitro (median D2R IRS 1.0 vs 8.0 for < 50% vs. > 50% inhibition by cabergoline and median SST5 IRS 3.5 avs. 12.0 for < 50% vs. > 50% inhibition by pasireotide). In a subgroup, pasireotide inhibited prolactin secretion with comparable potency to cabergoline. Targeting SST5 with pasireotide may be a potential treatment modality for further clinical investigation in the treatment of a subset of DA resistant or intolerant prolactinomas.
PMCID:12583388
PMID: 41184667
ISSN: 1573-7403
CID: 5959552
Prostate Cancer Imaging Stewardship: a multi-modal, physician-centered intervention for guideline-concordant imaging
Makarov, Danil V; Thomas, Jerry K; Ciprut, Shannon; Rivera, Adrian J; Sherman, Scott E; Braithwaite, R Scott; Best, Sara L; Blakely, Stephen; D'Agostino, Louis A; Dahm, Philipp; Dash, Atreya; Leapman, Michael S; Leppert, John T; Sanchez, Alejandro; Shelton, Jeremy B; Tessier, Christopher D; Tenner, Craig T; Gold, Heather T; Shedlin, Michele G; Zeliadt, Steven B
BACKGROUND:Inappropriate imaging to stage low-risk prostate cancer is considered low-value care. Determining the effectiveness of a theory-based intervention, Prostate Cancer Imaging Stewardship (PCIS), to promote guideline-concordant imaging. METHODS:A stepped-wedge, cluster-randomized trial, PCIS, was conducted between March 2018 and March 2021 at ten Veterans Health Administration medical centers (VAMC) initially selected for prostate cancer volume, geographic diversity, and willingness to participate. Intervention initiation at sites were randomized in 3-month intervals. We enrolled 61 urology providers who treat prostate cancer at participating sites. Outcomes were assessed among 2,302 patients with incident prostate cancer aged 18-85 years. PCIS combines three evidence-based provider-focused behavior change strategies: 1) Clinical Reminder Order Check triggered when a provider attempted to order imaging for a patient with PSA < 20ng/mL; 2) VAMC-level academic detailing at initiation and every three months thereafter; 3) Audit and Feedback for providers to improve their imaging performance. The main outcome was guideline-discordant nuclear medicine bone scan (NMBS) imaging for low-risk prostate cancer patients. RESULTS:NMBS imaging would be consistent with National Comprehensive Cancer Network guidelines in 878 patients (38%) and inconsistent in 1424 patients (62%). Among patients not requiring NMBS, 141/690 (20.4%) received guideline-discordant imaging (ie, NMBS ordered) during Control compared to 109/734 (14.9%) during Intervention (OR = 0.54, p = .04). Among patients requiring a NMBS, 29/425 (6.8%) did not receive one (ie, guideline-discordant imaging) during Control compared to 25/453 (5.5%) during the Intervention (OR = 1.36, p = .36). CONCLUSION/CONCLUSIONS:PCIS significantly reduced low-value, guideline-discordant NMBS imaging among low-risk prostate cancer patients without negatively affecting necessary imaging for high-risk patients. CLINICAL TRIALS REGISTRATION/BACKGROUND:NCT03445559.
PMID: 40796156
ISSN: 1460-2105
CID: 5907222
Consequences of Patient Denial at First Exemption Request for Cardiac Transplantation [Letter]
Alam, A; Golob, S; Patel, S; Fatma, N; Segev, D; Massie, A; Moussa, M; Flattery, E; Phillips, K; Wayda, B; Katz, J N; Stewart, D; Gentry, S; Goldberg, R I; Rao, S; Reyentovich, A; Moazami, N
PMID: 40691956
ISSN: 1557-3117
CID: 5901342
A Just Appraisal: Co-creating a New Health Equity Framework with Learners through Journal Club to Evaluate the Literature
Mgbako, Ofole; Gonzalez, Cristina M; Olagun-Samuel, Christine; Torres, Christian; Richardson, Safiya; Williams, Renee; Greene, Richard E; Ortiz, Robin
BACKGROUND:Health equity is receiving increased attention in medical education. However, guidance is often lacking on how to integrate health equity into routine medical education. Journal club presents an opportunity to deepen medical educators' and learners' understanding of health equity principles and use it as a lens through which to critically appraise the literature. AIM/OBJECTIVE:We present a health equity framework, iteratively co-created by faculty and learners, that can be applied in a journal club setting. SETTING/METHODS:Academic medical center in New York City, USA. PARTICIPANTS/METHODS:Faculty, residency program directors, medical students, and residents. PROGRAM DESCRIPTION/METHODS:Authors developed the health equity journal club framework during a medical student selective course. Learner and faculty applied the framework to journal club articles; their feedback informed revisions. Framework domains included authorship, ethics, methodology, language, peer review, and references. PROGRAM EVALUATION/RESULTS:Learner evaluations were overall positive, and 86% (n = 13) of responding residency program directors (n = 15) across 15 departments who were surveyed plan to use the framework moving forward. DISCUSSION/CONCLUSIONS:A health equity journal club framework applied to critical appraisal of the literature may facilitate health equity as a routine part of medical education. Co-creating the framework proved vital to inclusion of learner voices.
PMID: 40760378
ISSN: 1525-1497
CID: 5904892
Recent Advances in Primary Biliary Cholangitis Treatment
Das, Taranika Sarkar; Vuppalanchi, Raj
Primary biliary cholangitis (PBC) is a rare autoimmune liver disease that leads to chronic cholestasis and progressive liver dysfunction. It is often accompanied by extrahepatic symptoms such as pruritus and fatigue, which significantly impair the quality of life. Current treatment options include ursodeoxycholic acid, the standard first-line therapy, along with second-line agents like obeticholic acid, and recently approved seladelpar, and elafibranor. These treatments aim to alleviate symptoms, improve liver function, and slow disease progression. This article focuses on recently approved therapies for PBC, discusses the nuances in their use, and explores the investigational pipeline of novel therapies under development.
PMID: 41109695
ISSN: 1557-8224
CID: 5955442
Future Treatment Options for Managing Primary Sclerosing Cholangitis and Cholestatic Pruritus
Das, Taranika Sarkar; Vuppalanchi, Raj
Primary sclerosing cholangitis (PSC) is a rare disease, autoimmune in nature, characterized by biliary strictures, chronic cholestasis, and progressive liver dysfunction. While its pathophysiology differs from primary biliary cholangitis (PBC), therapeutic targets still focus on bile acid regulation. PSC currently has no approved therapies, although several novel agents are under investigation. Cholestatic pruritus, a significant symptom in PSC and PBC, is now recognized as an approvable indication, with emerging therapies showing promise. This article highlights the investigational pipeline for PSC and cholestatic itch.
PMID: 41109703
ISSN: 1557-8224
CID: 5955452
Non-invasive brain stimulation augmentation therapy for treatment-resistant schizophrenia: a systematic review and network meta-analysis
Wei, Yaohui; Lorenz, Carolin; Siafis, Spyridon; Schneider-Thoma, Johannes; Kim, David D; Wu, Hui; Nomura, Nobuyuki; Dong, Shimeng; Furukawa, Yuki; Zhu, Yikang; Bighelli, Irene; Hansen, Wulf-Peter; Vogelmann, Ulrike; Strube, Wolfgang; Li, Chunbo; Davis, John M; Smith, Robert C; Salanti, Georgia; Padberg, Frank; Leucht, Stefan
BACKGROUND/UNASSIGNED:Non-invasive brain stimulation (NIBS) provides adjunctive therapeutic options for individuals with schizophrenia if medications are insufficient to produce clinical response, but guidelines remain controversial on whether NIBS is effective, and which NIBS methods and targets are preferred. We aimed to compare the efficacy and safety of NIBS for treatment-resistant schizophrenia (TRS). METHODS/UNASSIGNED:This systematic review and network meta-analysis of randomised controlled trials investigated NIBS interventions, including electroconvulsive therapy, magnetic seizure therapy (MST), repetitive transcranial magnetic stimulation (rTMS), and transcranial electric stimulation (tES), as adjunctive treatment for TRS. We searched the Cochrane Schizophrenia Group's specialised register from inception to 2025.07.13, and three Chinese databases from inception to 2024.10.30. The primary outcome was overall symptoms, and adverse events were analysed as secondary outcomes. We synthesized the data using random-effects network meta-analysis. Sensitivity analyses examined the robustness of the findings and the effects of the detailed NIBS protocols. The protocol was pre-registered with PROSPERO (CRD42023410645) and published in a scientific journal. FINDINGS/UNASSIGNED:We identified 21710 references and included 78 trials with a total of 3416 participants (1216 women, 1733 men; mean age 37.06 years, range 25.55-48.38; ethnicity data were not recorded). Compared with sham stimulation, rTMS (SMD -0.47, 95% CI [-0.62; -0.31]) was more efficacious in improving overall symptoms; but not in a sensitivity analysis excluding studies from Chinese mainland (-0.19, [-0.38; 0.01]). No clear differences between rTMS specific protocols in terms of stimulation targets and protocols were detected. No clear differences were found for electroconvulsive therapy (-0.20, [-0.78; 0.37]), tES (-0.08, [-0.38; 0.22]), and MST (-0.30, [-1.73; 1.13]) compared to sham stimulation. Treatment as usual might be less efficacious than sham (1.13, [-0.13; 2.38]), based on indirect evidence. NIBS was generally safe (rTMS produced headaches and local reactions), but information about adverse events was rarely reported. INTERPRETATION/UNASSIGNED:rTMS may be efficacious in individuals with TRS, but this finding was driven mainly by studies from Chinese mainland. No clear differences were observed for electroconvulsive therapy, tES, and MST, but the findings were imprecise and inconclusive. FUNDING/UNASSIGNED:German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung/BMBF; 01KG2206).
PMCID:12589960
PMID: 41210378
ISSN: 2589-5370
CID: 5966442
Efficacy of the GLP-1 receptor agonist, semaglutide, in abstinence from illicit and nonprescribed opioids in an outpatient population with OUD: a randomized, double-blind, placebo-controlled clinical trial protocol
Freet, Christopher S; Shuler, Kirsten; Kawasaki, Sarah; Weintraub, Eric; Greenblatt, Aaron; Kladney, Mat; Nunes, Edward; Foster, Katrina L; Kong, Lan; Raja-Khan, Nazia; Cleveland, H Harrington; Grigson, Patricia S; Bunce, Scott C; Brick, Timothy R; Nyland, Jennifer E
BACKGROUND:Standard medications for opioid use disorder (MOUD) provide effective treatment pathways for recovery compared with no treatment or behavioral therapies alone. That said, people who continue to use non-prescribed opioids despite treatment with MOUD are at greater risk for high attrition and OUD-related harms. Novel, more effective approaches are needed for the treatment of OUD. To that end, glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide a promising option as a non-opioid pharmacological intervention for OUD. Observational studies suggest that GLP-1RAs decrease craving measures in a residential OUD population but no controlled clinical trials have been conducted to determine if GLP-1RAs increase opioid abstinence and reduce craving in individuals with OUD in an outpatient population. The purpose of the current protocol is to evaluate the potential for the GLP-1RA, semaglutide, to increase abstinence and reduce craving in an outpatient population enrolled in a MOUD program and continue to use non-prescribed opioids. METHOD/METHODS:This protocol is a randomized, double-blind, placebo-controlled clinical trial designed to test the efficacy of the GLP-1RA, semaglutide, in 200 participants enrolled in an outpatient MOUD program (n = 100 buprenorphine; n = 100 methadone) for the treatment of OUD. Outcomes include the probability of participants being abstinent from illicit and nonprescribed opioids, as well as measures of craving and days of drug use. Measures will be evaluated using urine toxicology screens and self-report assessments across 19 weeks during a screening visit (Study Week 1), 12 treatment visits (Study Weeks 2-13), a washout visit (Study Week 14), and a final follow-up visit (Study Week 19). DISCUSSION/CONCLUSIONS:This manuscript describes a phase II clinical protocol to collect data on the efficacy of a GLP-1RA, semaglutide, in persons enrolled in an MOUD program and with ongoing non-prescribed opioid use despite treatment with methadone or buprenorphine. Completion of the current project will support the feasibility of phase III clinical trials for further evaluation in larger outpatient OUD populations that may lead to a new indication for GLP-1RA as a novel and effective treatment for OUD. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov: NCT06548490. Registered 12 August 2024, https://clinicaltrials.gov/study/NCT06548490 .
PMID: 41168808
ISSN: 1940-0640
CID: 5961682
A Culturally and Linguistically Tailored Intervention to Improve Diabetes-Related Outcomes in Chinese Americans With Type 2 Diabetes: Pilot Randomized Controlled Trial
Liu, Jing; Cao, Jiepin; Shi, Yun; Sevick, Mary Ann; Islam, Nadia; Feldman, Naumi; Li, Huilin; Wang, Chan; Zhao, Yanan; Tamura, Kosuke; Levy, Natalie; Jiang, Nan; Zhu, Ziqiang; Wang, Yulin; Hong, Jia; Hu, Lu
BACKGROUND:levels. However, it remains unclear whether the CARE program also improves diabetes self-efficacy and psychosocial outcomes in the same study sample. OBJECTIVE:This is a secondary analysis to examine the potential efficacy of the CARE program on secondary outcomes, including diabetes self-efficacy, self-care activities, beliefs in diabetes self-care activities, and diabetes distress among Chinese Americans with T2D. METHODS:level of 7% or higher. Participants were recruited from various health care settings in New York City, including community health centers, private primary care providers, and NYU Langone Health and its affiliates, and were randomly assigned to either the CARE intervention group (n=30) or a waitlist control group (n=30). The intervention consisted of 2 culturally and linguistically tailored educational videos per week for 12 weeks, covering diabetes self-care topics such as healthy eating, physical activity, and medication adherence. These videos were delivered via the WeChat app. In addition, community health workers provided support calls to assist them in setting goals, problem-solving, and addressing social determinants of health barriers every 2 weeks. Secondary outcomes included patient self-reported diabetes self-efficacy, self-care activities, beliefs in diabetes self-care activities, and diabetes distress. Outcomes were assessed at baseline, 3 months, and 6 months. RESULTS:Participants had a mean age of 54.3 (SD 11.5) years and 62% (37/60) were male, 78% (47/60) were married, 58% (35/60) were employed, 70% (42/60) had a high school education or lower, and 88% (53/60) reported limited English proficiency. Intervention participants demonstrated statistically significant improvements in self-efficacy at 3 months (estimated difference in change: 8.47; 95% CI 2.44-14.5; adjusted P=.02), diabetes distress at 6 months (estimated difference in change: -0.43; 95% CI -0.71 to -0.15; adjusted P=.009), and adherence to a healthy diet at both 3 months (estimated difference in change: 1.61; 95% CI 0.46-2.75; adjusted P=.02) and 6 months (estimated difference in change: 1.64; 95% CI 0.48-2.81; adjusted P=.02). CONCLUSIONS:The culturally and linguistically tailored intervention showed promise in improving self-efficacy and diabetes self-care activities among Chinese Americans with T2D, warranting validation through a large-scale randomized controlled trial. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03557697; https://clinicaltrials.gov/study/NCT03557697.
PMID: 41144955
ISSN: 2291-5222
CID: 5960992
Correlates of asymptomatic sexually transmitted infections among marginalized women in the Dominican Republic
Chang, Michelle; Castor, Delivette; Heck, Craig J; Hernandez, Brian; Gomes, Angelina; Zucker, Jason; Wallach, Sara; Gelfond, Jonathan; Halpern, Mina; Donastorg, Yeycy; Perez Mencia, Martha; Lantigua, Giselle; Stonbraker, Samantha; Taylor, Barbara S; Amesty, Silvia
BackgroundSexually transmitted infections (STIs) continue to cause morbidity among women in resource-constrained settings, where asymptomatic infections are often overlooked due to syndromic management protocols. We investigated correlates of asymptomatic STIs among women in the Dominican Republic (DR).MethodsWe analyzed data collected from cisgender women in DR between 2015 and 2019. Classified groups included pregnant youth (PY), people with HIV (PWH), residents of bateyes (RB), and sex workers (SW). Nucleic acid amplification or rapid plasma reagin tests detected STIs (Chlamydia/Gonorrhoeae/Syphilis/Trichomonas). Asymptomatic comprised no self-reported vaginal discharge, dysuria, groin lymphadenopathy, and genital/anal pain/ulcers. Logistic regressions identified sociodemographic, clinical, and behavioral correlates.ResultsAmong 833 asymptomatic women (median age 29, IQR 19-37), 35% were PY, 27% PWH, 11% RB, and 27% SW. STI prevalence was 24%: most (61%) had Chlamydia and few (≤25%) had Gonorrhoea, Syphilis, or Trichomonas. Asymptomatic STI correlates included age ≤24 (Adjusted Odds Ratio [aOR] = 2.32, [1.65-3.28]), early (≤14) sexual debut (aOR = 1.56, [1.11-2.18]), greater mobility (aOR = 1.41, [1.01-1.97]), lack of regular doctor (aOR = 1.42, [1.01-1.99]), and drug use in last 6 months (aOR = 1.88, [1.07-3.26]).ConclusionsCorrelates of asymptomatic STIs-age, sexual debut, mobility, healthcare access, and drug use-should inform targeted screening and prevention efforts where diagnostic testing is not widely available.
PMID: 41118141
ISSN: 1758-1052
CID: 5956752