Faculty Bibliography

This post-hoc analysis of the ALLEGRO phase 2b/3 study (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral Janus kinase 3/TEC family kinase inhibitor, in patients with alopecia totalis (AT) and alopecia universalis (AU). Patients aged ≥ 12 years with alopecia areata (AA) and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (± 4-week 200-mg loading dose) or placebo for 24 weeks. In a subsequent 24-week extension period, the ritlecitinib groups continued their doses and patients initially assigned to placebo switched to ritlecitinib (200/50 or 50 mg daily). In this analysis, clinician- and patient-reported hair regrowth outcomes were assessed at weeks 24 and 48 in four AA subgroups: AT/AU, AT, AU, and non-AT/AU. Safety was monitored throughout. Of the 718 randomized patients, 151 (21%) and 147 (20%) were defined as having AT or AU, respectively. At week 24, Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp hair loss) response rates were higher in the ritlecitinib-treated AT/AU, AT, and AU groups (7%-14%, 7%-21%, and 4%-10%, respectively) vs the placebo group (0% in the AT/AU, AT, and AU groups). The proportions of patients with a SALT score of ≤20 increased through week 48 (AT/AU, 13%-31%; AT, 11%-27%; AU, 6%-41%). Additionally, at week 24, 25%-43%, 32%-42%, and 12%-50% of patients with AT/AU, AT, and AU, respectively, who received ritlecitinib achieved a moderately or greatly improved response based on the Patient Global Impression of Change scale. Response rates generally increased through week 48 and were similar across AA subgroups. In patients with AT/AU, ritlecitinib was well tolerated with a safety profile consistent with that of the overall AA population. Ritlecitinib demonstrated clinical efficacy, patient-reported improvement, and an acceptable safety profile in patients with AT and AU through week 48. A plain language summary of this study is available at https://doi.org/10.25454/pfizer.figshare.26879161. Clinicaltrials.gov: NCT03732807.

RATIONALE & OBJECTIVE/UNASSIGNED:In 2021, the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) updated the creatinine-based estimated glomerular filtration rate (eGFR) equation and removed the coefficient for race. The development and validation of this equation involved binarizing race into African American and non-African American, involving few Asian participants. This study aimed to examine the difference between the 2021 equation and the previous 2009 equation on CKD prevalence estimates in 2 Asian populations. STUDY DESIGN/UNASSIGNED:Observational study using 2 national surveys. SETTING & PARTICIPANTS/UNASSIGNED:Participants from the 2019 Korea National Health and Nutrition Survey and participants self-reported as Asian from the 2011-2020 US National Health and Nutrition Survey. EXPOSURE/UNASSIGNED:eGFR using 2009 and 2021 CKD-EPI creatinine equation. OUTCOMES/UNASSIGNED:or urine albumin-creatinine ratio ≥30 mg/g). ANALYTICAL APPROACH/UNASSIGNED:Sampling-weighted prevalence estimated using the 2009 and 2021 equations as well as the percentage of individuals with CKD G3+ using the 2009 equation being reclassified as not having CKD G3+ using the 2021 equation. RESULTS/UNASSIGNED:The prevalence of CKD estimated using the 2021 equation was 9.75% (95% confidence intervals [CI], 8.80-10.80%) in Koreans and 11.60% (95% CI, 10.23-13.13%) in US Asians. The prevalence of CKD estimated using the 2021 equation was slightly lower than that using the 2009 equation in both Korean and US Asian populations by 0.63% (95% CI, 0.44-0.90%) and 0.84% (95% CI, 0.52-1.34%), respectively. Furthermore, 32.8% and 30.2% of Koreans and US Asians with CKD G3-5, respectively, estimated using the 2009 equation were reclassified as not having CKD G3-5 when the eGFR was calculated using the 2021 equation. LIMITATIONS/UNASSIGNED:Measured GFR was not available. CONCLUSIONS/UNASSIGNED:Use of the 2021 CKD-EPI creatinine equation leads to a small decrease in CKD prevalence in both Korean and US Asian populations, and of similar magnitude, resulting in significant reclassification among those originally classified as having CKD G3+.

BACKGROUND/UNASSIGNED:In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting. OBJECTIVES/UNASSIGNED:The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial. DESIGN/UNASSIGNED:RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared with CP alone in patients with primary advanced or recurrent EC. METHODS/UNASSIGNED:Patients were randomized 1:1 to dostarlimab 500 mg, or placebo, plus CP every 3 weeks for 6 cycles, followed by dostarlimab 1000 mg, or placebo, every 6 weeks for up to 3 years. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events, version 4.03. RESULTS/UNASSIGNED:The safety population included 487 patients who received ⩾1 dose of treatment (241 dostarlimab plus CP; 246 placebo plus CP). Treatment-emergent AEs were experienced by 100% of patients in both arms. TRAEs occurred in 97.9% of the dostarlimab arm and 98.8% of the placebo arm.The most common TRAEs occurred at similar rates between arms and were mostly low grade. IrAEs occurred in 58.5% of patients in the dostarlimab arm and 37.0% of patients in the placebo arm. Dostarlimab- or placebo-related irAEs were reported in 40.7% of patients in the dostarlimab arm and 16.3% of the placebo arm. CONCLUSION/UNASSIGNED:The safety profile of dostarlimab plus CP was generally consistent with that of the individual components. Dostarlimab plus CP has a favorable benefit-risk profile and is a new standard of care for patients with primary advanced or recurrent EC. TRIAL REGISTRATION/UNASSIGNED:NCT03981796.

The incidence of substance use and behavioral addictions continues to increase throughout the world. The Global Burden of Disease Study shows a growing impact in disability-adjusted life years due to substance use. Substance use impacts families, communities, health care, and legal systems; yet, the vast majority of individuals with substance use disorders do not seek treatment. Within the United States, new legislation has attempted to increase the availability of buprenorphine, but the impact of substance use continues. Although medications and group support therapy have been the mainstay of treatment for substance use, lifestyle medicine offers a valuable adjunct therapy that may help strengthen substance use recovery through healthy neuroplastic changes.

Treatment of pregnancy-related venous thromboembolism is limited by considerations of the health risks to both the patient and fetus. Anticoagulation is the cornerstone treatment for pregnancy-related venous thromboembolism; however, early thrombus removal may be preferred for prompt symptom resolution and to decrease the risk of post-thrombotic syndrome. We report the successful treatment of a patient in the second trimester of pregnancy with symptomatic iliofemoral deep venous thrombosis and May-Thurner syndrome using percutaneous mechanical thrombectomy.

BACKGROUND/UNASSIGNED:Cow's milk allergy (CMA) is the most complex and common food allergy in infants. Elimination of cow's milk from the diet and replacement with a specialized formula for infants with cow's milk allergy who cannot be breastfed is an established approach to minimize the risk of severe allergic reactions while avoiding nutritional deficiencies. Given the availability of multiple options, such as extensively hydrolyzed cow's milk-based formula (eHF-CM), aminoacid formula (AAF), hydrolyzed rice formula (HRF), and soy formula (SF), there is some uncertainty regarding which formula might represent the most suitable choice with respect to health outcomes. The addition of probiotics to a specialized formula has also been proposed as a potential approach to possibly increase the benefit. We systematically reviewed specialized formulas for infants with CMA to inform the updated World Allergy Organization (WAO) DRACMA guidelines. OBJECTIVE/UNASSIGNED:To systematically review and synthesize the available evidence about the use of specialized formulas for the management of individuals with CMA. METHODS/UNASSIGNED:We searched from inception PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations, for randomized and non-randomized trials of any language investigating specialized formulas with or without probiotics. We included all studies irrespective of the language of the original publication. The last search was conducted in January 2024. We synthesized the identified evidence quantitatively or narratively as appropriate and summarized it in the evidence profiles. We conducted this review following the PRISMA, Cochrane methods, and the GRADE approach. RESULTS/UNASSIGNED:GG) showed no significant effect, as supported by low to very low CoE. CONCLUSIONS/UNASSIGNED:Currently available studies comparing eHF-CM, AAF, HRF, and SF provide very low certainty evidence about their effects in infants with IgE-mediated and non-IgE-mediated CMA. Our review revealed several limitations in the current body of evidence, primarily arising from concerns related to the quality of studies, the limited size of the participant populations and most importantly the lack of diversity and standardization in the compared interventions. It is therefore imperative for future studies to be methodologically rigorous and investigate a broader spectrum of available interventions. We encourage clinicians and researchers to review current World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines for suggestions on how to use milk replacement formulas in clinical practice and what additional research would be the most beneficial.

BACKGROUND/UNASSIGNED:Chronic pain is highly prevalent in US military Veterans, and pain interdisciplinary teams (IDTs) are the gold standard in pain care. There is no standard or guidance for how best to develop and implement pain interdisciplinary teams within complex health care systems. OBJECTIVES/UNASSIGNED:The purpose of this quality improvement project was to evaluate the effectiveness of the standard 9-step Lean 6 Sigma (LSS) methodology in redesigning a pre-existing VA outpatient pain clinic solely offering interventional pain services into an efficient, sustainable pain IDT program. METHODS/UNASSIGNED:The initial evaluation process at a VA Medical Center that primarily serves rural Veterans was redesigned with the a priori goal of developing an efficient, sustainable IDT program that decreased driving days (ie, in-person appointments) required for a comprehensive initial pain evaluation, decreased number of consults required for initial pain evaluations, increased the number of consults to Whole Health services, and increased compliance with policies and standards. Feedback from administrators, clinicians, and Veterans was used to identify inefficiencies then iteratively design, test, and finalize a redesigned service called the PREVAIL Interdisciplinary Team Track (PREVAIL IDT Track). Baseline data was collected for 1 year followed by sustainment data for 14 months. Results were analyzed using descriptive statistics. RESULTS/UNASSIGNED:PREVAIL IDT Track decreased the number of in-person appointments from 5 to 2, decreased consults required for evaluations from 5 to 1, increased the number of unique consults to Whole Health education classes, and made the VA fully compliant with policies and standards. To date, 486 Veterans have participated in the redesigned program, including 167 graduates and 212 current enrollees in this sustained clinical program. CONCLUSION/UNASSIGNED:The success of PREVAIL IDT Track suggests that LSS may be a promising method for redesigning sustainable pain IDTs in VA that improve efficiency.

Achieving a sustained virologic response (SVR) through direct-acting antivirals for hepatitis C virus (HCV) infection significantly reduces the long-term risk of hepatocellular carcinoma (HCC), particularly in patients with advanced fibrosis (F3) or cirrhosis (F4). However, despite this improvement, the risks associated with HCC and the optimal surveillance strategies for patients who have achieved SVR remain topics of debate. This controversy is compounded by challenges in reliably staging liver fibrosis non-invasively, especially at advanced fibrosis (F3), and the unclear cost-effectiveness, modality, frequency, and duration of HCC surveillance in individuals with SVR but without cirrhosis. These factors contribute to significant variations in surveillance guidelines recommended by different professional societies. Therefore, there is a pressing need for an optimal surveillance strategy that is both simplified and cost-effective to facilitate wider adoption by clinicians. This review article evaluates the existing data, addresses ongoing controversies, and aims to provide new perspectives on HCC surveillance strategies for patients who have achieved SVR from HCV.

OBJECTIVE/UNASSIGNED:To better characterize the cochlear apex in relation to surgically relevant landmarks to guide surgeons and improve procedural success of apical electrode placement. STUDY DESIGN/UNASSIGNED:Retrospective image analysis. SETTING/UNASSIGNED:Tertiary referral center. PATIENTS/UNASSIGNED:Cochlear implant recipients with available preoperative computed tomography (CT) imaging. INTERVENTION/UNASSIGNED:None. MAIN OUTCOME MEASURE/UNASSIGNED:Cochlear dimensions and cochlear apex distance measures to surgically relevant middle ear landmarks and critical structures. RESULTS/UNASSIGNED:Eighty-two temporal bone CT scans were analyzed utilizing multiplanar reformats. The average lateral width of promontory bone over the cochlear apex was 1.2 mm (standard deviation [SD], 0.3). The anteroposterior distance from the round window (avg, 4.2 mm; SD, 0.5), oval window (avg, 3.3 mm; SD, 0.3), cochleariform process (avg, 2.3; SD, 0.5), and superior-inferior distance from the cochleariform process (avg, -0.9; SD, 0.8) to the cochlear apex were measured. The relationship of the cochlear apex to critical structures was highly variable.A newly developed stapes vector was created and found to mark the posterior/superior boundary of the apex in 94% of patients. When a vector parallel to the stapes vector was drawn through the round window, it marked the anterior/inferior boundary of the cochlear apex in 89% of patients. CONCLUSIONS/UNASSIGNED:This study assists in characterizing cochlear apex anatomy and its relation to surrounding structures as a means of improving procedural accuracy and reducing trauma during apical cochleostomy. Understanding both distance relationships and expected boundaries of the apex could help to inform future surgical approaches.