Faculty Bibliography

OBJECTIVE:To examine the associations between patient out-of-pocket (OOP) costs and nonadherence to glucagon-like peptide 1 receptor agonists (GLP-1a), and the consequent impact on adverse outcomes, including hospitalizations and emergency department (ED) visits. RESEARCH DESIGN AND METHODS/METHODS:This retrospective cohort study used MarketScan Commercial data (2016-2021). The cohort included nonpregnant adults aged 18-64 years with type 2 diabetes who initiated GLP-1a therapy. Participants were continuously enrolled in the same private insurance plan for 6 months before the prescription date and 1 year thereafter. Exposures included average first 30-day OOP costs for GLP-1a, categorized into quartiles (lowest [Q1] to highest [Q4]). Primary outcomes were the annual proportion of days covered (PDC) for GLP-1a and nonadherence, defined as PDC <0.8. Secondary outcomes included diabetes-related and all-cause hospitalizations and ED visits 1 year post-GLP-1a initiation. RESULTS:Among 61,907 adults who initiated GLP-1a, higher 30-day OOP costs were associated with decreased adherence. Patients in the highest OOP cost quartile (Q4: $80-$3,375) had significantly higher odds of nonadherence (odds ratio [OR]1.25; 95% CI 1.19-1.31) compared with those in Q1 ($0-$21). Nonadherence was linked to increased incidence rates of diabetes-related hospitalizations or ED visits (incidence rate ratio [IRR] 1.86; 95% CI 1.43-2.42), cumulative length of hospitalization (IRR 1.56; 95% CI 1.41-1.72), all-cause ED visits (IRR 1.38; 95% CI 1.32-1.45), and increased ED-related costs ($69.81, 95% CI $53.54-$86.08). CONCLUSIONS:Higher OOP costs for GLP-1a were associated with reduced adherence and increased rates of adverse outcomes among type 2 diabetes patients.

We present a case highlighting innominate vein reconstruction for resection of Hurthle cell carcinoma with complex vascular invasion. A 69-year-old man presented with a rapidly enlarging neck mass, dysphagia and dysphonia. Workup demonstrated a 11.2 × 7.0 × 6.5 cm Hurthle cell carcinoma invading the oropharynx and superior mediastinum. We proceeded with left thyroid lobectomy and modified left radical neck dissection. Median sternotomy, resection of the left clavicular head, and partial resection of the left manubrium were performed to circumferentially expose the innominate vein. Tumor thrombus was extruded from the innominate vein followed by patch angioplasty, which remains patent 14 months postoperatively.

Atopic dermatitis (AD) is a common, chronic inflammatory skin disease that affects both children and adults. Atopic dermatitis is characterized by pruritus, erythema, induration, and scale, which can present with other conditions that may mimic or complicate AD; often leading to diagnostic challenges. Differential diagnoses include seborrheic dermatitis, contact dermatitis, psoriasis, infections, inflammatory/autoimmune disorders, cutaneous T-cell lymphoma, and immunodeficiency-related dermatoses; to name a few. This review article focuses on AD and its associated cutaneous comorbid diseases. Familiarity with the spectrum of these diseases and their distinguishing features is crucial for diagnostic accuracy and to optimize patient management.

AIM/OBJECTIVE:This study aimed to explore the efficacy of MRI-based radiomics models, employing various machine learning techniques, in the preoperative prediction of the digital subtraction angiography (DSA) classification of venous malformations (VMs). MATERIALS AND METHODS/METHODS:In this retrospective study, 160 VM lesions from 153 children were categorized into a training set (n=128) and a testing set (n=32). Radiomic features were extracted from preoperative MRI scans. Feature selection was executed using the intraclass correlation coefficient test, z-scores, the K-best method, and the least absolute shrinkage and selection operator. Diverse MRI sequences and machine learning methods underpinned the development of the radiomics models. The models' efficacy was evaluated using receiver operating characteristic curves and the area under the curve (AUC). RESULTS:Out of 4528 radiomic features derived from CET1 and T2 images, 9 features were significantly associated with DSA classification differentiation. The most effective model for predicting VMs' DSA classification incorporated these 9 features and employed a random forest classifier. This model achieved an AUC of 0.917 in the training set and an excellent discrimination AUC of 0.891 in the testing set. CONCLUSION/CONCLUSIONS:The random forest model, utilizing CET1 and T2 sequences, exhibited outstanding predictive performance in the preoperative distinction of VMs' DSA classification.

OBJECTIVE:To evaluate the association between implementation of "Pathways to Success" and quality among beneficiaries cared for in Shared Savings Program accountable care organizations (ACOs). STUDY SETTING AND DESIGN/METHODS:Medicare initiated "Pathways to Success" in 2019 that required upside-risk only ACOs in Shared Savings Program to transition to a two-sided risk model and prior two-sided ACOs to assume even greater financial responsibility. We examined the association between Pathways and ACO-targeted (hospitalizations for congestive heart failure [CHF] and all-cause 30-day readmissions) and nontargeted (all-cause emergency department visits without hospitalization for CHF and hospital observation stays) quality measures, using a difference-in-differences framework. DATA SOURCES AND ANALYTIC SAMPLE/UNASSIGNED:Data were extracted from a 20% sample of national Medicare data from 2018 to 2020. This study included 810,070 beneficiary-quarters in 514 ACOs, and 813,855 beneficiary-quarters never attributed to an ACO (i.e., controls). PRINCIPAL FINDINGS/RESULTS:Implementation of Pathways was not associated with significant relative changes in the quarterly number of CHF admissions (decreasing from 97.98 to 82.04 per 1000 beneficiaries in ACOs; differential change = 3.51 quarterly CHF admissions per 1000 beneficiaries, 95% CI, -4.82 to 11.85) or the quarterly number of emergency department visits for CHF (decreasing from 110.90 to 97.50 per 1000 beneficiaries in ACOs; differential change = 6.47 quarterly CHF emergency department visits per 1000 beneficiaries, 95% CI, -3.71 to 16.64). However, quarterly rates of 30-day all-cause readmissions increased slightly by 0.61% points (95% CI, 0.23 to 0.98; unadjusted readmissions increased from 14.49% to 14.81% in ACOs) after Pathways implementation. Observation stays remained unchanged (differential change = -0.16% points, 95% CI, -0.33 to 0.02; unadjusted observation stays increased from 3.64% to 3.94% in ACOs) after the launch of Pathways. CONCLUSIONS:Medicare's Pathways to Success, which introduced two-sided risk, was not associated with improvement in select quality measures.

BACKGROUND:Bruton's tyrosine kinase inhibitors (BTKis) are central to the medical management of chronic lymphocytic leukemia (CLL). However, accumulating data suggest an important association with cardiovascular (CV) adverse events (AEs), including arrhythmias, hypertension, and bleeding, in patients with CLL and other hematological malignancies treated with this therapeutic class. Data from comparative trials with BTKis suggest second-generation agents, eg, acalabrutinib and zanubrutinib, may be associated with fewer CV AEs than first-in-class BTKi ibrutinib. METHODS:PubMed and the proceedings of key hematology congresses were searched for relevant information using broad search terms including CLL, BTKi, and toxicity. RESULTS:When managing patients with CLL, screening before and during treatment to assess CV risk is suggested to guide decision-making. Due to the increased toxicity with ibrutinib, the second-generation BTKis are now preferred (per the NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines®]). For patients with a high CV-risk, the decision between second-generation BTKi or a time-limited alternative, like venetoclax plus an anti-CD20 monoclonal antibody, should be made on an individual basis after patient consultation and consideration of the presenting characteristics of CLL in any given patient. The management of anticoagulant/antiplatelet medication during BTKi treatment requires specific attention, with coexistent medications being carefully assessed before starting a BTKi to reduce the risk of bleeding. For patients with a new-onset or worsening CV events during BTKi therapy, management may involve temporarily stopping the BTKi or switching to another class of therapy. To ensure the best outcomes, a collaborative care approach is essential, and some patients may need to be referred to a cardiologist/cardio-oncologist for specialist management. CONCLUSION/CONCLUSIONS:Baseline and ongoing CV risk assessment, careful monitoring, management, and a multidisciplinary team approach are all critical to ensure optimal oncologic and CV outcomes for patients with CLL receiving BTKis.

BACKGROUND AND OBJECTIVE/OBJECTIVE:The vascular groove (VG) is no longer considered a resection margin but rather a surface of involvement. The clinical significance of an isolated VG+ remains debated. Therefore, this study evaluates the impact of isolated VG+, with or without vein resection, on overall survival (OS) and disease-free survival (DFS) following pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS:A retrospective analysis of 247 patients (2006-2019) was conducted. Patients were categorized into three groups: R0 resection (tumor > 1 mm from all margins, n = 168), VG+ without vein invasion (+VGnoVI, n = 66), and positive vein involvement with direct tumor invasion into the vein wall (+VGwithVI) (n = 13). Kaplan-Meier estimates assessed OS and DFS, while multivariable analyses identified recurrence and survival predictors. RESULTS:+VGnoVI group showed higher rates of local recurrence (OR 2.68, p = 0.002) compared to the R0 group. However, no significant differences were observed in DFS (R0: 17 months; +VGnoVI: 18 months; +VGwithVI: 21 months, p = 0.68) or OS (R0: 27 months; +VGnoVI: 29 months; +VGwithVI: 30 months, p = 0.98) across groups. CONCLUSIONS:A positive vascular groove, whether isolated or associated with vein invasion, does not compromise OS or DFS compared to R0 resections.

Placental abruption has classically been defined as the premature separation of a normally located placenta before delivery of the fetus. Traditionally, this diagnosis was based on clinical symptoms, including vaginal bleeding, pain, and fetal distress. This definition, however, preceded the advent of obstetric ultrasound. Ultrasound frequently identifies various hemorrhagic lesions, such as retroplacental, subchorionic, intraamniotic, intraplacental, and preplacental hematomas in both symptomatic and asymptomatic patients. These variable ultrasound findings lead to new challenges as to what to define as an abruption, particularly in the absence of symptoms. This ambiguity in defining placental abruption affects clinical decision-making and hinders our understanding of the pathophysiology of abruption, presenting challenges in studying abruption. It is likely that these varying sonographic findings may precede the classic presentation of vaginal bleeding and pain and therefore are often concealed abruptions. This commentary highlights the importance of developing clear diagnostic guidelines for placental abruption, given its association with severe outcomes including a high rate of perinatal mortality and maternal morbidity. We aim to elucidate the complexities of ultrasound diagnosis in placental abruption, advocating for precise criteria to better guide clinical practice. We propose that these ultrasound findings of hemorrhagic placental lesions after 20 weeks of gestation in asymptomatic patients should be considered part of the spectrum of abruption, while in symptomatic patients should be taken as confirmation of the diagnosis of abruption.

Belzutifan is a hypoxia-inducible factor-2α (HIF-2α) inhibitor that received FDA approval in 2021 for treating cancers resulting from von Hippel-Lindau (VHL) disease, including clear cell renal cell carcinoma (ccRCC), followed by approval in 2023 for sporadic ccRCC that has progressed through multiple lines of therapy. HIF-2α is a promising drug target, as VHL is commonly inactivated in ccRCC, which results in HIF-2α-mediated signaling that is considered central to tumorigenesis. Belzutifan has demonstrated efficacy in clinical trials in the first-line and subsequent line settings, and in combination with tyrosine kinase inhibitors. Despite being overall well tolerated, belzutifan has a distinct safety profile because of its unique mechanism of action. Anemia was the most common adverse event observed in clinical trials and is considered an on-target effect. Hypoxia is also frequently observed and commonly results in dose reductions, treatment discontinuation, and supplemental oxygen use. This review summarizes the rates of hypoxia seen in clinical trials of belzutifan in ccRCC. As the cause of hypoxia is not well understood, this review also discusses possible mechanisms of hypoxia based on preclinical studies of the HIF pathway and HIF-2α inhibitors. Finally, this review proposes monitoring and management recommendations for clinicians prescribing belzutifan to ccRCC patients.