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Purpose: The United States Medical Licensing Examination (USMLE) is an examination series required for allopathic physician licensure in the United States (US). USMLE content is created and maintained by the National Board of Medical Examinations (NBME). The specialty composition of the USMLE and NBME taskforce members involved in the creation of examination content is currently unknown. Methods: Using the 2021 USMLE and 2021 NBME Committees and Task Forces documents, we determined each member's board-certified primary specialty and involvement in test material development committees who we dubbed "test writers". Total active physicians by primary specialty were recorded from the 2020 Physician Specialty Data Report published by the Association of American Medical Colleges (AAMC). Descriptive statistics and chi-square analysis were used to analyze the cohorts. Results: The USMLE and NBME test writer primary specialty composition was found to be significantly different compared to the US active physician population (USMLE χ2[32] = 172, p <.001 and NBME χ2[32] = 200, p <.001). Only nineteen specialties were represented within USMLE test writers, with three specialties being proportionally represented. Two specialties were represented within NBME test writers. Obstetrics and Gynecology physicians were proportionally represented in USMLE but not within NBME test writers. Internal Medicine (IM) accounts for the largest percentage of all USMLE test writers (60/197, 30%) with an excess representation of 31 individuals. Conclusions: There is an imbalance in the specialty representation of USMLE and NBME test writers compared to the US active physician population. These findings may have implications for the unbiased and accurate portrayal of topics in such national examinations; thus, future investigation is warranted. [ABSTRACT FROM AUTHOR]

Background: Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS. Methods: Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies. Discussion: This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS. Trial registration: NCT05301283. Trial status: The trial started recruitment on March 17, 2022. [ABSTRACT FROM AUTHOR]

Introduction Human papillomavirus-related (HPV +) oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence and presents diagnostic challenges given its unique clinical presentation. Objective The purpose of the present study is to characterize the impact of the unique clinical presentation of HPV-related OPSCC on delays in diagnosis. Methods Retrospective review of presenting symptoms and clinical characteristics of 284 patients with OPSCC treated from 2002–2014. Delay in diagnosis was defined as the presence of any of the following: multiple non-diagnostic fine needle aspirate (FNA) biopsies; two or more courses of antibiotic therapy; surgery with incorrect preoperative diagnosis; evaluation by an otolaryngologist without further workup; or surgery without definitive postoperative diagnosis. Results p16+ tumors demonstrated a distinct clinical presentation that more commonly involved a neck mass (85.1% versus 57.3% of p16-; p < 0.001) and less frequently included odynophagia (24.6% versus 51.7% of p16-; p < 0.001). Patients who experienced diagnostic delay were more likely to have p16+ tumors (77.7% delayed versus 62.8% not delayed; p = 0.006). p16+ primary tumors were more likely to be undetectable by physical examination of the head and neck including flexible laryngoscopy (19.0% versus 6.7% of p16-; p = 0.007) and more frequently associated with nondiagnostic FNA biopsies of a cervical nodal mass (11.8% versus 3.4% of p16-, p = 0.03). Conclusions Compared with non-HPV related OPSCC, the unique clinical presentation and characteristics of HPV+ OPSCC are associated with an increased incidence of diagnostic delay. Targeted education of appropriate care providers may improve time to diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The role of radiation therapy (RT) varies across hematologic malignancies (HM). Radiation oncology (RO) resident comfort with specific aspects of HM patient management is unknown. The International Lymphoma RO Group (ILROG) assessed resident HM training opportunities and interest in an HM away elective. RO residents (PGY2-5) in the Association of Residents in RO (ARRO) database (n = 572) were emailed an anonymous, web-based survey in January 2019 including binary, Likert-type scale (1 = not at all, 5 = extremely, reported as median [interquartile range]), and multiple-choice questions. Of 134 resident respondents (23%), 86 (64%) were PGY4/5 residents and 36 (27%) were in larger programs (≥ 13 residents). Residents reported having specialized HM faculty (112, 84%) and a dedicated HM rotation (95, 71%). Residents reported "moderate" preparedness to advocate for RT in multidisciplinary conferences (3 [2–3]); make HM-related clinical decisions (3 [2–4]); and critique treatment planning (3 [2–4]). They reported feeling "moderately" to "quite" prepared to contour HM cases (3.5 [3–4]) and "quite" prepared to utilize the PET-CT five-point scale (4 [3–5]). Overall, residents reported feeling "moderately" prepared to treat HM patients (3 [2–3]); 24 residents (23%) felt "quite" or "extremely" prepared. Sixty-six residents (49%) were potentially interested in an HM away elective, commonly to increase comfort with treating HM patients (65%). Therefore, HM training is an important component of RO residency, yet a minority of surveyed trainees felt quite or extremely well prepared to treat HM patients. Programs should explore alternative and additional educational opportunities to increase resident comfort with treating HM patients. [ABSTRACT FROM AUTHOR]

The treatment of central and ultracentral lung tumors with radiotherapy remains an ongoing clinical challenge. The risk of Grade 5 toxicity with ablative radiotherapy doses to these high-risk regions is significant as shown in recent prospective studies. Magnetic resonance (MR) image-guided adaptive radiotherapy (MRgART) is a new technology and may allow the delivery of ablative radiotherapy to these high-risk regions safely. MRgART is able to achieve this by utilizing small treatment margins, real-time gating/tracking and on-table plan adaptation to maintain dose to the tumor but limit dose to critical structures. The process of MRgART is complex and has nuances and challenges for the treatment of lung tumors. We outline the critical steps needed for appropriate delivery of MRgART for lung tumors safely and effectively. [ABSTRACT FROM AUTHOR]

Introduction: To develop a radiomic‐based model to predict pathological complete response (pCR) and outcome following neoadjuvant chemoradiotherapy (NACRT) in oesophageal cancer. Methods: We analysed 68 patients with oesophageal cancer treated with NACRT followed by esophagectomy, who had staging 18F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET) and computed tomography (CT) scans performed at our institution. An in‐house data‐chjmirocterization algorithm was used to extract 3D‐radiomic features from the segmented primary disease. Prediction models were constructed and internally validated. Composite feature, Fc = α * FPET + (1 − α) * FCT, 0 ≤ α ≤ 1, was constructed for each corresponding CT and PET feature. Loco‐regional control (LRC), recurrence‐free survival (RFS), metastasis‐free survival (MFS) and overall survival (OS) were estimated by Kaplan–Meier analysis, and compared using log‐rank test. Results: Median follow‐up was 59 months. pCR was achieved in 34 (50%) patients. Five‐year RFS, LRC, MFS and OS were 67.1%, 88.5%, 75.6% and 57.6%, respectively. Tumour Regression Grade (TRG) 0–1 indicative of complete response or minimal residual disease was significantly associated with improved 5‐year LRC [93.7% vs 71.8%; P = 0.020; HR 0.19, 95% CI 0.04–0.85]. Four sepjmirote pCR predictive models were built for CT alone, PET alone, CT+PET and composite. CT, PET and CT+PET models had AUC 0.73 ± 0.08, 0.66 ± 0.08 and 0.77 ± 0.07, respectively. The composite model resulted in an improvement of pCR predicting power with AUC 0.87 ± 0.06. Stratifying patients with a low versus high radiomic score showed clinically relevant improvement in 5‐year LRC favouring low‐score group (91.1% vs. 80%, 95% CI 0.09–1.77, P = 0.2). Conclusion: The composite CT/PET radiomics model was highly predictive of pCR following NACRT. Validation in larger data sets is warranted to determine whether the model can predict clinical outcomes. [ABSTRACT FROM AUTHOR]

aims, and 4.5% involved medical claims only. Conclusion: Males and minors were overrepresented among plaintiffs in ocular trauma litigation. Most cases involved open globe injuries, often complicated by retained intraocular foreign bodies and endophthalmitis. Analysis of malpractice litigation in ophthalmic trauma calls attention to commonly litigated scenarios to improve clinical practice and to inform risk management. [ABSTRACT FROM AUTHOR]

Purpose: To guide risk management in uveitis.Methods: Retrospective review of malpractice verdicts, rulings, and settlements.Results: The WestLaw® database was reviewed for lawsuits related to uveitis in the United States from 1930-2014. Twenty-five cases met inclusion criteria, and 48% of these were infectious. Overall, 64% of outcomes favored the defendant ophthalmologist. The most common diagnoses were viral retinitis (28%), iritis (12%), syphilis (8%), and toxoplasmosis (8%). Seven suits (28%) were resolved by settlement, with mean adjusted indemnities of $724,302 (median, $409,390; range, $127,837-2,021,887). Two cases (8%) resulted in plaintiff verdict, with adjusted awards of $1,399,800 and $630,799.Conclusions: Despite being a rare diagnosis, viral retinitis (especially acute retinal necrosis) is the most common clinical entity associated with litigation in uveitis and should be considered early. Educating patients about potential adverse events, early testing for syphilis, and maintaining a positive relationship may also minimize risk. [ABSTRACT FROM AUTHOR]

Purpose: Types 1 and 2 granular corneal dystrophies (GCD) are primarily associated with accumulation of the R555W and R124H mutant transforming growth factor β-inducible proteins (TGFBIp) in corneal stroma, respectively. However, specific components of TGFBIp responsible for granular deposits have not been delineated. This study was undertaken to identify the mutant TGFBIp components potentially responsible for GCD. Methods: Recombinant TGFBIp of wild-type (WT) and three mutants, R124C, R124H, and R555W, were generated in HEK293FT cells. WT and TGFBIp mutants were collected from cell lysates. Immunoblot analyses were performed with five different antibodies directed against various regions of WT TGFBIp. Results: WT and TGFBIp mutants showed differential reactivities with these antibodies. In contrast to our prior observation in purified WT and TGFBIp mutants, TGFBIp from cell lysates were less prone to polymerize. A unique 35 kD fragment was detected in cell lysates of R555W and R124H, but not in those of WT or R124C, by a commercial antibody raised against amino acids (a.a.) 199-406 of TGFBIp. Conclusions: Monomeric and polymeric WT and TGFBIp mutants were observed in vitro. The 35 kD fragment found only in R555W and R124H, but not in WT and R124C cell lysates, is likely a degraded TGFBIp derived from the central domain of these mutants and this fragment may be contributory to the nonamyloid granular deposits observed in GCD 1 and 2. [ABSTRACT FROM AUTHOR]

The implementation of the radiation oncology alternative payment model (RO-APM) has raised concerns regarding the development of MRI-guided adaptive radiotherapy (MRgART). We sought to compare technical fee reimbursement under Fee-For-Service (FFS) to the proposed RO-APM for a typical MRI-Linac (MRL) patient load and distribution of 200 patients. In an exploratory aim, a modifier was added to the RO-APM (mRO-APM) to account for the resources necessary to provide this care. Traditional Medicare FFS reimbursement rates were compared to the diagnosis-based reimbursement in the RO-APM. Reimbursement for all selected diagnoses were lower in the RO-APM compared to FFS, with the largest differences in the adaptive treatments for lung cancer (−89%) and pancreatic cancer (−83%). The total annual reimbursement discrepancy amounted to −78%. Without implementation of adaptive replanning there was no difference in reimbursement in breast, colorectal and prostate cancer between RO-APM and mRO-APM. Accommodating online adaptive treatments in the mRO-APM would result in a reimbursement difference from the FFS model of −47% for lung cancer and −46% for pancreatic cancer, mitigating the overall annual reimbursement difference to −54%. Even with adjustment, the implementation of MRgART as a new treatment strategy is susceptible under the RO-APM. [ABSTRACT FROM AUTHOR]