Faculty Bibliography

BACKGROUND:No empirical data support the 54-58mm external diameter of intravaginal rings (rings) currently available and in development for contraception and other indications. Understanding how external diameter affects preference, adherence, and acceptability is critical for optimizing future product development. OBJECTIVES/OBJECTIVE:Our primary objectives were to determine which of three non-medicated rings of differing external diameters was preferred and yielded the highest adherence. Secondary objectives were comparing acceptability, patterns of adherence, and safety of the three rings. STUDY DESIGN/METHODS:In an open-label, three-way crossover trial, healthy, HIV-uninfected, monogamous, sexually active, non-pregnant,18-40-year-old cisgender women and their male partners in Atlanta, GA and the Bronx, NY were randomly assigned to the sequence of using three non-medicated silicone rings (46mm, 56mm, 66mm external diameters)continuously for approximately 30 days each (90 days total; November 2021-December 2022). We tested whether end of study preference for any of the three rings was greater than 0.33 (binomial proportion, exact test). We used mixed-effect regression models with random intercepts by participant to compare adherence (ring never out for longer than 30 minutes in 24 hours); and probability of removals (including reasons for removal), expulsions, and the ring being out of the vagina all day, per ring, per day of use with the 56mm ring as the reference group; and to compare scores on a novel 19-item acceptability scale with items related to ease and experience of use, and impact on sex. RESULTS:23/24 women completed the study (median age 26.7 years [SD 3.78]). Most were college graduates (92%), White (63%), non-Hispanic (79%), single (79%), and nulliparous (92%). At study end, 59% preferred the smallest (46mm) ring versus 18% each for the 56mm and 66mm rings (p=0.0045). The proportion of participants who were adherent did not differ significantly by ring (46mm, 78%; 56mm, 75%; 66mm, 59%; p=0.30), however, odds of expulsion were higher for the 46mm (OR 5.72, 95% CI: 1.25-26.1) and 66mm (OR 25.9, 95% CI: 6.11-109) rings than the 56mm ring. The 66mm ring also had greater odds of being out (removal or expulsion, any length of time) than the 56mm ring (OR 6.50, 95% CI 3.46-12.2). Mean acceptability scale scores were identical (4.54/5) for the 46mm and 56mm (smallest and medium) rings and significantly higher than the largest, 66mm ring (3.94/5; p<0.001). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Although the 46mm ring was preferred by more women and had higher rates of adherence compared to the other two rings, the 56mm ring was rated as equally acceptable with significantly fewer reports of expulsions/removals compared to the other two rings. These data confirm that the current 54-58mm diameter of vaginal rings on the market and in development is acceptable and performs well. Future studies should explore the effect of other mechanical attributes, such as compressibility, on preference, adherence, and acceptability, as well as investigating ring characteristics in other populations.

OBJECTIVES/OBJECTIVE:To assess the reliability of rectal MRI radiomic features across reader expertise level, image segmentation technique, and timing of rectal MRI. MATERIAL AND METHODS/METHODS:This retrospective single-institutional study included consecutive patients with rectal adenocarcinoma who underwent total neoadjuvant therapy from January 2018 to June 2018. Baseline and restaging rectal MRI T2-weighted images were segmented independently by six radiologists (two fellows, two non-rectal radiologists, and two rectal radiologists). Four segmentation strategies were used and varied by image segmentation technique and timing of rectal MRI: (a) baseline volume of interest (VOI), (b) baseline region of interest (ROI), (c) restaging VOI, and (d) restaging ROI. Inter-reader agreement on each extracted radiomic feature was evaluated using the intra-class correlation coefficient (ICC). RESULTS:Among 24 patients (16 men; median age, 56 years [interquartile range: 49-62]), 1,595 radiomic features were extracted. Baseline VOI segmentation achieved the highest inter-reader agreement rate, with 68 % (1,079/1,595) of radiomic features having an ICC > 0.7. Restaging ROI segmentation achieved the worst inter-reader agreement rate, with only 26 % (415/1,595) of radiomic features having an ICC > 0.7. First-order statistics and Gray Level Co-occurrence Matrix (GLCM) feature subgroups showed high inter-reader agreement rates, and the application of 'Square Root' and 'LOG Sigma' filters resulted in improved inter-reader agreement rates relative to original images. The expertise level of radiologists performing the segmentations did not affect the distribution of inter-agreement rates according to image segmentation technique or timing of rectal MRI. CONCLUSIONS:Radiomic features were more reliable when extracted from baseline (vs. restaging) rectal MRIs and using 3D volume of interest (vs. 2D region of interest) segmentation, independent of the expertise level of the radiologists performing the segmentation. CLINICAL RELEVANCE STATEMENT/CONCLUSIONS:Radiomic studies on rectal MRI employ various segmentation strategies and few assess their impact on reproducibility. Establishing the optimal segmentation method enhances radiomics model generalizability, potentially bridging the gap in clinical translation and improving clinical management of patients.

BACKGROUND:People experiencing homelessness (PEH) with opioid use disorder (OUD) are at high risk of overdose yet less likely to enroll and stay engaged in standard-of-care treatment for OUD, opioid agonist medication for OUD (MOUD), particularly methadone treatment. Engaging this group in treatment is a public health priority, yet little is known about the experiences of PEH enrolled in MOUD. We sought to understand the housing experiences and perspectives of PEH engaged in methadone treatment using mixed quantitative and qualitative methods. METHODS:We recruited individuals with past or present experiences of homelessness who were engaged in methadone treatment at a low-barrier opioid treatment program (OTP) in Connecticut between December 2022 and May 2023. Participants completed surveys about their demographics, resource needs, and housing and healthcare experiences. One-to-one qualitative interviews using a semi-structured interview guide queried participants' experiences with homelessness. Descriptive statistics summarize study variables using Python. The interviews were transcribed and analyzed using thematic analysis. RESULTS:Of 50 participants (19 women, 31 men, mean age 44 years), 80 % reported experiencing homelessness for over a year. Participants reported experiencing a mean of 56.6 months without permanent, stable housing and a mean of 2.4 periods of homelessness in the past 3 years. Thematic analysis yielded three primary themes that described the intersectional identity of an individual with OUD and experiencing homelessness: 1) Challenges created by homelessness (e.g., transportation barriers limiting access to the OTP); 2) Personal barriers to exiting homelessness (e.g., struggling with continued substance use); and 3) Structural barriers to exiting homelessness (e.g., difficulty navigating the housing system). CONCLUSIONS:PEH enrolled in methadone treatment face substantial barriers related to their OUD and housing status as well as many structural, social, and health-related vulnerabilities. Future efforts to address these vulnerabilities in clinical settings may enhance treatment engagement and should be examined to potentially attenuate the very high risk of overdose that PEH face. Challenges created by homelessness, personal barriers to exiting homelessness, and structural barriers to exiting homelessness are potential targets for methadone treatment programs to better tailor treatment and improve engagement and outcomes.

OBJECTIVE:To assess the association of race/ethnicity and education status on time to intervention and the total number of interventions in pediatric patients with microtia undergoing hearing intervention and external ear reconstruction. METHODS:A retrospective chart review was performed in pediatric patients diagnosed with congenital ear deformities evaluated by an otolaryngologist or audiologist from January 1, 2013 to December 1, 2021 at a large surgical institution. Variables analyzed included demographics, patient conditions, time to surgery, and number of surgeries. Statistical analysis included analysis of variance, chi-squared tests, and multivariate regression. RESULTS:Disparities were identified in reconstructive microtia repair, with non-White patients having an increased number of external ear reconstructive surgeries (p = 0.004), with Black patients average 2 external ear reconstructive surgeries, Hispanic patients 1.74 surgeries, while White patients averaged 0.812 surgeries. All non-White patients also demonstrated increased total number of surgeries (1.94 Asian, 2.57 Black, 2.11 Hispanic, 3.29 Other/Unknown, vs 1.23 White, p = 0.007) and total number of interventions (2.17 Asian, 2.71 Black, 2.37 Hispanic 3.43 Other/Unknown, vs 1.56 White, p = 0.02) as compared to White patients. In multivariate regression analysis, race was a significant factor influencing the number of reconstructive and overall surgeries, while the presence of aural atresia was the strongest predictor for requiring additional hearing surgery. CONCLUSION/CONCLUSIONS:An increased number of interventions and surgeries were seen amongst non-White patients with microtia. Further investigation is warranted to understand the socioeconomic factors associated with pediatric microtia surgery.

BACKGROUND:We sought to estimate the prevalence of synthetic cannabinoid use and characteristics of people who use in the US general population. METHODS:We compared the prevalence of past-year synthetic cannabinoid use in 2023 to 2021 among individuals ages ≥ 12 surveyed via the National Survey on Drug Use and Health (N = 173,808). We also compared prevalence according to demographic and drug use characteristics and delineated correlates of past-year use. RESULTS:Synthetic cannabinoid use increased from 0.17 % in 2021 to 0.26 % in 2023, a 50.0 % increase (p = .042) (0.25 % prevalence in 2021-2023 overall). The largest increases were among those aged ≥ 35 (by 255.3 %), those with an annual family income of < $20,000 (by 242.1 %), and those who used methamphetamine in the past year (by 184.6 %) (Ps < .05). In our final multivariable model, those with less than a high school diploma (aOR=2.20, 95 % CI: 1.12-4.32) and those with past-year cannabis use (aOR=13.55, 95 % CI: 8.36-21.95) and use disorder (aOR=26.03, 95 % CI: 17.70-38.29) were at higher odds for synthetic cannabinoid use, as were people with methamphetamine use (aOR=3.08, 95 % CI: 1.18-8.01) and use disorder (aOR=4.74, 95 % CI: 2.17-10.37), and prescription opioid misuse (aOR=1.75, 95 % CI: 1.05-2.93) and use disorder (aOR=3.22, 95 % CI: 1.78-5.82). CONCLUSION/CONCLUSIONS:Survey data suggest that synthetic cannabinoid use is rare but increasing, particularly among people of lower socioeconomic status and people who use other drugs. Cannabis use disorder in particular is associated with higher odds for use. Research is needed to determine if overreporting is occurring due to confusion with emerging cannabis products.

The objective of this study was to establish recommendations for thromboprophylaxis in patients with endogenous Cushing's syndrome (CS), addressing the elevated risk of venous thromboembolism (VTE) associated with hypercortisolism. A Delphi method was used, consisting of 4 rounds of voting and subsequent discussions. The panel included 18 international experts from 11 countries and 4 continents. Consensus was defined as ≥75% agreement among participants. Recommendations were structured into the following categories: thromboprophylaxis, perioperative management, and VTE treatment. Consensus was reached on several critical areas, resulting in 14 recommendations. Key recommendations include: thromboprophylaxis should be considered at time of CS diagnosis and continued for 3 months after biochemical remission, provided there are no obvious contraindications. The standard weight-based prophylactic dose of low molecular-weight heparin is the preferred agent for thromboprophylaxis in patients with CS. Additionally, perioperatively and around inferior petrosal sinus sampling, thromboprophylaxis should be reconsidered if not already initiated at diagnosis. For VTE treatment, extended thromboprophylaxis is advised continuing for 3 months after Cushing is resolved. These Delphi consensus-based recommendations aim to standardize care practices and enhance patient outcomes in CS by providing guidance on thromboprophylaxis, including its initiation and continuation across various disease states, as well as the preferred agents to use. The panel also highlighted key areas for further research, particularly regarding the use of direct oral anticoagulants in CS and the management of mild CS and mild autonomous cortisol secretion. Additionally, the optimal duration of anticoagulant prophylaxis following curative treatment remains uncertain.

Pathogenic variants resulting in protein phosphatase 2A (PP2A) dysfunction result in mild to severe neurodevelopmental delay. PP2A is a trimer of a catalytic (C) subunit, scaffolding (A) subunit, and substrate binding/regulatory (B) subunit, encoded by 19 different genes. De novo missense variants in PPP2R5D (B56δ) or PPP2R1A (Aα) and de novo missense and loss-of-function variants in PPP2CA (Cα) lead to syndromes with overlapping phenotypic features, known as Houge-Janssens syndrome (HJS) types 1, 2, and 3, respectively. Here, we describe an additional condition in the HJS spectrum in 26 individuals with variants in PPP2R5C, encoding the regulatory B56γ subunit. Most changes were de novo and of the missense type. The clinical features were well within the HJS spectrum with strongest resemblance to HJS type 1, caused by B56δ variants. Common features were neurodevelopmental delay and hypotonia, with a high risk of epilepsy, behavioral problems, and mildly dysmorphic facial features. Head circumferences were above average or macrocephalic. The degree of intellectual disability was, on average, milder than in other HJS types. All variants affected either substrate binding (2/19), C-subunit binding (2/19), or both (15/19). Five variants were recurrent. Catalytic activity of the phosphatase was variably affected by the variants. Of note, PPP2R5C total loss-of-function variants could be inherited from a non-symptomatic parent. This implies that a dominant-negative mechanism on substrate dephosphorylation or general PP2A function is the most likely pathogenic mechanism.

OBJECTIVES/OBJECTIVE:While the use of endovascular intervention for peripheral artery disease (PAD) has expanded in recent years, there remains relatively few studies focused on the endovascular treatment of isolated popliteal artery occlusive disease. The popliteal artery presents a particular challenge for endovascular intervention due to the constant flexion at the knee. We sought to assess the outcomes for endovascular management of isolated popliteal artery occlusive disease based on type of intervention performed. METHODS:The Vascular Qualitative Initiative (VQI) database was queried for patients with isolated popliteal artery occlusive disease who underwent endovascular intervention from January 2011 to December 2019. Patients were excluded from analysis if they did not have Medicare FFS entitlement, had a history of prior intervention in the ipsilateral limb, or had vessels treated in addition to the popliteal artery. Patients were stratified into groups based on their initial presenting symptom (claudication vs. chronic limb threatening ischemia (CLTI)) and were analyzed by endovascular procedure performed (plain old balloon angioplasty (POBA) vs. adjunctive stent/atherectomy). The POBA group underwent only plain balloon angioplasty whereas the adjunctive stent/atherectomy group underwent any type of balloon angioplasty and adjunctive stenting or atherectomy or both. The primary outcome was amputation-free survival, a composite outcome of freedom from major amputation and/or death. RESULTS:A total of 1,740 patients met criteria for analysis who underwent endovascular intervention for isolated popliteal artery occlusive disease. Among patients with claudication, the amputation-free survival rate was significantly higher at 1 year and 3 years for patients treated with adjunctive stent/atherectomy compared to POBA (1 year: 94.2% vs. 88.9%, p = 0.03; 3 years: 83.0% vs. 76.6%, p = 0.04). This difference appeared to be driven by mortality, as mortality was significantly better for adjunctive stent/atherectomy compared to POBA (1 year: 4.6% vs. 10.2%, p = 0.01; 3 years: 15.4% vs. 23.3%, p = 0.02), whereas major amputation rates were not significantly different. However, multivariable analysis showed that use of adjunctive stent/atherectomy was not independently associated with improved amputation-free survival (adjusted HR 0.74, 95% CI 0.48-1.16, p = 0.19). In the CLTI group, amputation-free survival rates were not significantly different for patients treated with adjunctive stent/atherectomy compared to POBA (1 year: 65% vs. 64.6%, p = 0.78; 3 years: 47.1% vs. 42.6%, p = 0.30). Re-intervention rates were not statistically different when stratified by use of adjunctive therapies in either the claudication or CLTI groups. CONCLUSION/CONCLUSIONS:Our results suggest that across all patients with isolated popliteal artery occlusive disease, amputation-free survival rates were comparable regardless of endovascular treatment modality. As expected, amputation-free survival for patients presenting with claudication was favorable compared to those with CLTI, and was driven primarily by mortality. Re-intervention rates were similar across all patients regardless of treatment modality. This study underscores the clinical challenge of treating isolated popliteal artery occlusive disease and stresses the need for further study of adjunctive modalities in treating complex lesions.

PURPOSE OF REVIEW/UNASSIGNED:Dysphagia is a common medical condition among the geriatric population that can significantly impact a patient's quality of life. The manifestations, diagnosis, and treatment of esophageal dysphagia differ greatly based on the underlying etiology, especially in older individuals who may have accompanying complex medical comorbidities. This review explores the intricacies of esophageal dysphagia in the older population and how they are managed. RECENT FINDINGS/UNASSIGNED:Novel modalities, like the functional luminal imaging probe (FLIP) and timed barium esophagram (TBE), are now woven into our diagnostic schemas for esophageal dysphagia. Studies have also looked at the safety profile of available therapeutic interventions for older individuals. There are newer, less invasive treatment options, including radiofrequency application (RFA) and transoral incisionless fundoplication (TIF) for GERD management, that may benefit the geriatric population. SUMMARY/UNASSIGNED:In this review, we discuss the most likely etiologies of esophageal dysphagia in the elderly population. We then explore a diagnostic schema and highlight treatment choices based on diagnosis. Our review specifically explores the risks and benefits of management options in more medically complex geriatric patients.