A Model Using Clinical and Endoscopic Characteristics Identifies Patients at Risk for Eosinophilic Esophagitis According to Updated Diagnostic Guidelines.

BACKGROUND AND AIMS: Updated diagnostic guidelines for eosinophilic esophagitis (EoE) have eliminated the requirement for a proton pump inhibitor (PPI) trial, but there are no models to identify patients with EoE based on these new criteria. We aimed to develop a predictive model for diagnosis of EoE based on the updated EoE diagnostic guidelines. METHODS: We performed a secondary analysis of a prospective study of adult patients referred for outpatient esophagogastroduodenoscopy at University of North Carolina who had symptoms of esophageal dysfunction; patients with prevalent EoE were excluded. We analyzed data from 206 EoE cases (mean age 40.1, 62.6% male, 93.2% white) and 306 controls (mean age 52.3, 37.9% male, 79.7% white). We built predictive models for case-control status, using clinical, endoscopic, and histologic features, and defining EoE by either the new or historical definition of PPI non-response. Model discrimination was assessed by the area under the receiver-operator characteristic curve (AUC). RESULTS: Before endoscopy, younger age, male sex, history of atopic condition or food allergy, and dysphagia identified patients with EoE with an AUC of 0.83. When we included endoscopy findings suggestive of EoE, the model identified patients with EoE with an AUC of 0.92; this increased to 0.99 when histology was included. CONCLUSION: We developed a model to identify patients with EoE, without a trial of PPIs, based on updated diagnostic guidelines. Clinical features and endoscopic findings identified patients with EoE with an AUC of 0.92-even without histologic data and in the absence of dysphagia. This model can be used to select patients with upper gastrointestinal symptoms but without dysphagia for early diagnostic endoscopy. The model can also be used to identify cases of EoE when eosinophil counts are greater than 15 in biopsies but other causes of esophageal eosinophilia cannot necessarily be excluded.

Generic Measures of Quality of Life Are Not Correlated with Disease Activity in Eosinophilic Esophagitis.

BACKGROUND: The relationship between histologic disease activity in eosinophilic esophagitis (EoE) and generic measures of quality of life (QoL) is unclear. AIMS: To determine differences in QoL in adults with EoE based on histologic activity and assess changes in QoL over time. METHODS: We performed an analysis of prospectively collected data from patients in the University of North Carolina EoE Registry. Patients were categorized with histologically active (≥ 15 eosinophils per high-power field [eos/hpf]) or inactive (< 15 eos/hpf) disease. Dysphagia severity was measured with a Likert scale. QoL was measured with 36-Item Short Form (SF-36), compared between active and inactive groups, and assessed longitudinally. RESULTS: Of 147 EoE cases, those with inactive disease (n = 56) reported less dysphagia severity (3.2 vs. 1.9; p = 0.003) and had lower endoscopic severity (3.8 vs. 1.0; p < 0.001) than those with active disease (n = 91). While SF-36 scores did not differ between active and inactive status, lower mental component scores (MCS) were seen in patients treated with empiric dietary elimination (44.9 vs. 50.8; p = 0.005). Dysphagia severity was negatively correlated with both physical component score (PCS) (r = -0.33; p < 0.001) and MCS (r = -0.18; p = 0.03). Despite more cases achieving histologic response over time, SF-36 scores did not improve on either raw or adjusted analyses. CONCLUSION: QoL measured by SF-36 in EoE was similar regardless of histologic disease activity and was in the range of population averages. General QoL metrics like the SF-36 do not appear to have substantial utility in EoE.

Clinical and Molecular Factors Associated With Histologic Response to Topical Steroid Treatment in Patients With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Few factors have been identified that can be used to predict response of patients with eosinophilic esophagitis (EoE) to topical steroid treatment. We aimed to determine whether baseline clinical, endoscopic, histologic, and molecular features of EoE can be used to predict histologic response. METHODS: We collected data from 97 patients with EoE, from 2009 through 2015, treated with a topical steroid for 8 weeks; 59 patients had a histologic response to treatment. Baseline clinicopathologic features and gene expression patterns were compared between patients with a histologic response to treatment (<15 eos/hpf) and non-responders (≥15 eos/hpf). We performed sensitivity analyses for alternative histologic response definitions. Multivariate logistic regression was performed to identify predictive factors associated with response to therapy, which were assessed with area under the receiver operator characteristic (AUROC) curves. RESULTS: Baseline dilation was the only independent predictor of non-response (odds ratio [OR], 0.30; 95% CI, 0.10-0.89). When an alternate response (<1 eos/hpf) and non-response (<50% decrease in baseline eos/hpf) definition was used, independent predictors of response status were age (OR, 1.08; 95% CI, 1.02-1.14), food allergies (OR, 12.95; 95% CI, 2.20-76.15), baseline dilation (OR, 0.17; 95% CI, 0.03-0.88), edema or decreased vascularity (OR, 0.20; 95% CI, 0.04-1.03), and hiatal hernia (OR, 0.07; 95% CI, 0.01-0.66). Using these 5 factors, we developed a predictive model that discriminated complete responders from non-responders with an AUROC of 0.88. Baseline gene expression patterns were not associated with treatment response and did not change with different histologic response thresholds. CONCLUSIONS: In an analysis of 97 patients with EoE, we found dilation to be the only baseline factor associated with non-response to steroid treatment (<15 eos/hpf). However, a model comprising 5 clinical, endoscopic, and histologic factors identified patients with a complete response (<1 eos/hpf). A baseline gene expression panel was not predictive of treatment response at any threshold.

Heartburn and dyspepsia symptom severity improves after treatment and correlates with histology in adults with eosinophilic esophagitis.

Non-dysphagia symptoms, such as heartburn and dyspepsia, are poorly characterized in adults with eosinophilic esophagitis (EoE). It is unclear if treatment improves these symptoms. The aim of this paper was to assess (i) heartburn and dyspepsia symptom severity in adult EoE patients using validated symptom measures; (ii) change in symptoms after treatment; and (iii) symptom association with endoscopic and histologic features. In a prospective cohort of adult EoE patients who were not responsive to proton pump inhibitor therapy, non-dysphagia symptoms were assessed with heartburn items from the validated GERD-HRQL (gastroesophageal reflux disease health-related quality of life) and SODA (severity of dyspepsia assessment) instruments. Subjects completed the questionnaires at baseline and after treatment. Association of baseline symptoms with endoscopic and histologic features, and before and after treatment with diet or topical steroids, was assessed. Eighty-six EoE patients (mean age 39 years, 57% male, 95% white) completed a baseline questionnaire and 62 completed the follow-up questionnaire. The mean baseline GERD-HRQL score was 4.5 ± 6.5 and the mean total SODA score was 41.0 ± 12.6. At baseline, there was a weak but significant correlation between peak eosinophils and the SODA score (r = 0.28; p = 0.03) and no association between heartburn and SODA scores and endoscopic or other histologic findings. After treatment, there was a decrease in GERD-HRQL heartburn (4.3 vs. 2.6; p = 0.04) and SODA (49.5 vs. 35.5; p = 0.04) scores in histologic responders, but not in nonresponders. In a prospective cohort of EoE patients, baseline eosinophils positively correlated with dyspepsia severity. Heartburn and dyspepsia symptoms improved after treatment in histologic responders.

Medical Student Exposure to Integrated Behavioral Health.

OBJECTIVE: Integrated behavioral health (IBH) allows for effective care delivery for patients with mental health and behavioral health disorders in primary care settings. This study assesses the state of exposure current medical students have to the IBH model in family medicine clerkships, in order to augment the readiness of students to participate in IBH as developing professionals. METHODS: Clerkship directors at US and Canadian medical schools with a required family medicine run course (n = 141) were asked to estimate the percentage of students exposed to IBH in their clerkships, as part of the Council of Academic Family Medicine Educational Research Alliance (CERA) 2016 survey. RESULTS: The response rate was 86% (n = 118). Forty-four percent of clerkship directors reported that 0-20% of students are exposed to the IBH model in their clerkships. A comparison of schools with low and high exposure showed no significant differences among clerkship characteristics. CONCLUSIONS: A majority of medical students in the USA and Canada are not exposed to IBH models during their primary care clerkship. Larger systematic studies are needed to elucidate the steps necessary to prepare graduating medical students to collaborate in IBH models.

Minority Tax on Medical Students: A Review of the Literature and Mitigation Recommendations.

BACKGROUND AND OBJECTIVES: Accreditation standards for MD- and DO-granting institutions require medical schools to recruit a diverse student body and educate students about diverse groups of patients. The minority tax is a summary of responsibilities assigned to racial and ethnic underrepresented faculty to achieve diversity, equity, and inclusion in medical institutions in addition to their typical academic workload. This article provides a narrative review of medical students' experiences of the minority tax and recommendations on how medical educators can support an equitable learning environment by eliminating the minority tax. METHODS: We searched the PubMed, Web of Science, and Scopus databases, Google Scholar, and medical society websites, blogs, and fora for terms, including minority tax, medical students, and undergraduate medical education. We included publications if they discussed the underrepresented in medicine medical students' experiences of the minority tax. RESULTS: Our search yielded six peer-reviewed original research articles and six publications of commentaries, opinion pieces, or news pieces. Students who were underrepresented in medicine reported spending more hours on diversity efforts compared with students who were not underrepresented; moreover, students reported that they had to sacrifice academic excellence in order to fulfill these additional diversity duties. CONCLUSIONS: The minority tax among medical students constitutes an unequitable and unjust barrier to career advancement, and it likely represents an early cause of attrition in the pipeline of underrepresented in medicine academic faculty. Medical educators can enact specific recommendations to eliminate or mitigate the minority tax experience for medical students.

SHARPening Residency Selection: Implementing a Systematic Holistic Application Review Process.

PROBLEM: Traditional metrics used in residency application review processes are systematically biased against applicants from minoritized communities that are underrepresented in medicine (URiM). These biases harm not just URiM applicants but also residency programs and patients. Although several residency programs have implemented holistic reviews to mitigate these biases, few tested tools exist that can be adapted and implemented in a wide variety of settings within academic medicine. APPROACH: This article describes advances made in the third year of a longitudinal, ongoing quality improvement project that used the A3 framework to improve recruitment of URiM residents to a family medicine residency program. The authors devised a systematic holistic application review process (SHARP) to determine which applicants to invite to interview with the program. SHARP's development began in August 2019, and after significant discussion with program leadership and iterations of rubric refinement, the program adopted SHARP in September 2020 to review applications for the 2021 application cycle. OUTCOMES: Compared with the 2016 to 2020 period before SHARP implementation, data from the 2021 and 2022 residency application cycles after SHARP implementation showed a significant increase in the proportion of interviewed candidates who identify as URiM (from 23% to 38%, P < .001) and matched candidates who identify as URiM (from 27% to 62%, P = .004). There was also a notable increase in the number and diversity of reviewers who evaluated applicants to the program. NEXT STEPS: SHARP is a promising tool to mitigate the effects of racism and other biases against URiM applicants to residency programs. Residency programs across specialties may benefit from adopting SHARP and adapting it based on their own goals and priorities.

Racial differences in glucose control among patients with type 2 diabetes: a survey on dietary temptations, coping, and trust in physicians.

OBJECTIVE: A quantitative evaluation of self-care behaviors, psychosocial stressors, and patient relationships to health care to better understand racial disparities in these domains. RESEARCH DESIGN AND METHODS: A cross-sectional study of adult patients with type 2 diabetes in University of Pennsylvania Healthcare System who had a HbA1c test within one month of survey administration. The survey instrument included among other items, the Dieter's Inventory of Eating Temptations Self-Efficacy instrument (DIET-SE), the Jalowiec Coping Scale (JCS), and the Trust in Physician (TIP) scale. RESULTS: 332 individuals completed the survey. Poor glucose control was significantly associated with Black race, lower income level, other demographic variables, non-perfect medication adherence, and poorer diet quality. It was also associated with lower self-efficacy to resist social dietary temptations, and among White patients it was associated was decreased use of a confrontive coping style. However, these factors did not explain the racial differences in glucose control between Blacks and Whites. CONCLUSIONS: Interventions aimed at dietary temptations, coping styles, or trust in physicians may not reduce racial disparities in glucose control. However, interventions that focus on dietary temptations may positively affect all diabetic patients.

Endometrial adenocarcinoma presenting in a voided urine cytology specimen: Case report.

Though the primary diagnostic utility of urine cytology is in the detection of high grade urothelial carcinoma, malignancies other than those of urinary tract origin may also be present. Direct invasion of the bladder by an adjacent neoplasm, metastasis from a distant primary, or inadvertent contamination during specimen collection may all result in nonurothelial tumor cells being present in a urine cytology specimen. Here, we report a case of endometrial adenocarcinoma that was first identified in a voided urine specimen collected for the routine evaluation of hematuria. The presence of cohesive clusters with apparent glandular differentiation raised the possibility of a nonurothelial neoplasm and prompted an additional workup. Immunohistochemical stains performed on cell block material demonstrated that the glandular cells were positive for PAX8 and negative for GATA3, suggestive of gynecologic origin. A subsequent endometrial curettage and hysterectomy revealed endometrial adenocarcinoma. When faced with papillary groups in a voided urine specimen, the cytopathologist must remember to consider a broad differential diagnosis to include malignancies outside of the urinary tract. It was our awareness of valuable clinical information and keen cytologic assessment which allowed for an accurate diagnosis in the setting of this unexpected finding.

Lipoblastomatosis: An unusual midline neck mass in a young child.

Lipoblastomatosis is an extremely rare condition and is often not recognized prior to final pathologic analysis. In this case, a two-year-old female child presented with a non-tender, submental midline neck mass which had enlarged very slowly over the course of five months. The differential diagnosis included lipoma, lymphatic malformation, and thyroglossal duct cycst and a surgical excision was planned. The child was consented for a possible Sistrunk procedure if necessary. Intraoperatively, the mass was adherent to the hyoid bone and clear mucoid drainage was noted during resection leading the team to further weight the possibility of thyroglossal duct cyst and proceed with a Sistrunk procedure. Ultimately, final pathology revealed the diagnosis of lipoblastomatosis.

Decline in circulating viral and human tumor markers after resection of head and neck carcinoma.

BACKGROUND: DNA sequencing panels can simultaneously quantify human and viral tumor markers in blood. We explored changes in levels of plasma tumor markers following surgical resection of head and neck carcinoma. METHODS: In preresection and postresection plasmas, targeted DNA sequencing quantified variants in 28 human cancer genes and levels of oncogenic pathogens (human papillomavirus [HPV], Epstein-Barr virus [EBV], Helicobacter pylori) from 21 patients with head and neck squamous cell carcinoma. RESULTS: Preresection, 11 of 21 patients (52%) had detectable tumor markers in plasma, most commonly TP53 mutation or HPV genome. Several days postresection, levels fell to undetectable in 8 of 10 evaluable patients, while two high-stage patients retained circulating tumor markers. CONCLUSIONS: Modern sequencing technology can simultaneously quantify human gene variants and oncogenic viral genomes in plasma. Falling levels of cancer-specific markers upon resection can help identify viral and human markers to track at subsequent timepoints as a means to evaluate efficacy of interventions.

CRTC1/MAML2 directs a PGC-1α-IGF-1 circuit that confers vulnerability to PPARγ inhibition.

Mucoepidermoid carcinoma (MEC) is a life-threatening salivary gland cancer that is driven primarily by a transcriptional coactivator fusion composed of cyclic AMP-regulated transcriptional coactivator 1 (CRTC1) and mastermind-like 2 (MAML2). The mechanisms by which the chimeric CRTC1/MAML2 (C1/M2) oncoprotein rewires gene expression programs that promote tumorigenesis remain poorly understood. Here, we show that C1/M2 induces transcriptional activation of the non-canonical peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) splice variant PGC-1α4, which regulates peroxisome proliferator-activated receptor gamma (PPARγ)-mediated insulin-like growth factor 1 (IGF-1) expression. This mitogenic transcriptional circuitry is consistent across cell lines and primary tumors. C1/M2-positive tumors exhibit IGF-1 pathway activation, and small-molecule drug screens reveal that tumor cells harboring the fusion gene are selectively sensitive to IGF-1 receptor (IGF-1R) inhibition. Furthermore, this dependence on autocrine regulation of IGF-1 transcription renders MEC cells susceptible to PPARγ inhibition with inverse agonists. These results yield insights into the aberrant coregulatory functions of C1/M2 and identify a specific vulnerability that can be exploited for precision therapy.

Mucosal Eosinophilia Is an Independent Predictor of Vedolizumab Efficacy in Inflammatory Bowel Diseases.

BACKGROUND: Peripheral and mucosal eosinophilia may be associated with more aggressive disease in inflammatory bowel disease (IBD) patients. Vedolizumab blocks T lymphocytes, eosinophil adhesion, and extravasation in the gastrointestinal tract. It is not known if mucosal eosinophilia is a predictor for the therapeutic efficacy of vedolizumab. METHODS: This was a retrospective cohort study of IBD patients with ileal or colonic biopsies who were off steroids before starting vedolizumab. Biopsies were rereviewed by pathologists, and mean eosinophil density was quantified. Patient characteristics and steroid-free clinical response 6 months after beginning vedolizumab were determined. Features were compared between nonresponders and responders, and multivariable logistic regression was performed to identify predictors of clinical response. RESULTS: Of 251 IBD patients starting vedolizumab therapy, 65 patients (48% Crohn's disease, 52% ulcerative colitis) met inclusion criteria. All IBD patients not responding to vedolizumab were more likely to have a higher baseline mean eosinophil count (340 ± 156 vs 236 ± 124; P = 0.004), be previously exposed to an anti-TNF (96% vs 56%; P = 0.001), and be male (58% vs 28%; P = 0.02). Mean eosinophil counts were significantly increased in colonic biopsies in UC nonresponders (438 ± 149 vs 299 ± 145; P = 0.01). A similar trend was seen in CD nonresponders. On multivariable analysis, colonic eosinophil density and prior anti-TNF exposure-and the combination of both-were independent predictors of response. CONCLUSION: In ulcerative colitis, colonic eosinophilia and prior anti-TNF exposure were independent predictors of 6-month clinical nonresponse to vedolizumab. Mucosal eosinophil density as a novel biomarker should be explored in larger patient cohorts.Aside from the previous anti-TNF exposure, eosinophil density in the colon of patients with UC is a negative predictor for a steroid-free long-term response to vedolizumab. The degree colonic eosinophilia may be a novel biomarker that should be further explored.

Post-radiation angiosarcoma of the uterine cervix.

•Angiosarcoma is a rare endothelial malignancy associated with radiation exposure.•Very rarely, angiosarcoma has been reported to arise in the uterine cervix.•We report the first case of post-radiation angiosarcoma of the cervix.

Cryptococcus deuterogattii VGIIa Infection Associated with Travel to the Pacific Northwest Outbreak Region in an Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibody-Positive Patient in the United States.

The region encompassing the Pacific Northwest (PNW), Vancouver Island, Oregon, and Washington has been the location of an ongoing Cryptococcus gattii outbreak since the 1990s, and there is evidence that the outbreak is expanding along the West Coast into California. Here we report a clinical case of a 69-year-old, HIV-negative man from North Carolina who was diagnosed with a fungal brain mass by magnetic resonance imaging (MRI) and pathology. He had traveled to Seattle and Vancouver 3 years earlier and to Costa Rica 4 months prior to presentation. Phenotypic evidence showed that the fungal mass isolated from the patient's brain represented C. gattii In agreement with the phenotypic results, multilocus sequence typing (MLST) provided genotypic evidence that assigned the infecting organism within the C. gattii species complex and to the C. deuterogattii VGIIa clade. Whole-genome sequencing revealed >99.99% identity with the C. deuterogattii reference strain R265, indicating that the infecting strain is derived from the highly clonal outbreak strains in the PNW. We conclude that the patient acquired the C. gattii infection during his travel to the region 3 years prior and that the infection was dormant for an extended period of time before causing disease. The patient tested positive for anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, supporting earlier reports that implicate these autoantibodies as a risk factor associated with C. gattii infection.IMPORTANCE Mortality rates associated with C. gattii infections are estimated to be between 13% and 33%, depending on an individual's predisposition, and C. gattii has caused at least 39 deaths in the PNW region. There have been four other international travel cases reported in patients from Europe and Asia with travel history to the PNW, but this report describes the first North American traveler who acquired C. deuterogattii infection presenting within the United States and the first case of a C. deuterogattii outbreak infection associated with anti-GM-CSF autoantibodies. Early and accurate diagnoses are important for disease prevention and treatment and for control of infectious diseases. Continual reporting of C. deuterogattii infections is necessary to raise awareness of the ongoing outbreak in the PNW and to alert travelers and physicians to the areas of endemicity with potential risks.

HIV-positive smokers considering quitting: differences by race/ethnicity.

OBJECTIVE: To better characterize smoking in HIV-positive individuals and to identify critical components of a targeted smoking cessation intervention for multiethnic HIV-positive smokers. METHODS: Differences in baseline characteristics of 444 HIV-positive smokers were examined by race, and a multivariate linear regression model evaluated factors associated with nicotine dependence in an HIV-positive population, with a particular emphasis on race/ethnic differences. RESULTS: Low smoking self-efficacy and higher contemplation of quitting were predictive of greater nicotine dependence. An interaction between age and race was noted, with older Hispanic Americans less likely to be nicotine dependent. CONCLUSIONS: Efforts should be made to tailor smoking cessation intervention content to HIV-positive racial/ethnic minority groups.

Integrated Behavioral Health Care in Family Medicine Residencies A CERA Survey.

BACKGROUND AND OBJECTIVES: Behavioral health integration (BHI) in primary care settings is critical to mental health care in the United States. Family medicine resident experience in BHI in family medicine residency (FMR) continuity clinics is essential preparation for practice. We surveyed FMR program directors to characterize the status of BHI in FMR training. METHODS: Using the Council of Academic Family Medicine Educational Research Alliance (CERA) 2017 survey, FMR program directors (n=478, 261 respondents, 54.6% response rate) were queried regarding the stage of BHI within the residency family medicine center (FMC), integration activities at the FMC, and the professions of the BH faculty. BHI was characterized by Substance Abuse and Mental Health Services Agency (SAMHSA) designations within FMRs, and chi-square or ANOVA with Tukey honest significant difference (HSD) post hoc testing was used to assess differences in reported BHI attributes. RESULTS: Program directors reported a high level of BHI in their FMCs (44.1% full integration, 33.7% colocated). Higher levels of BHI were associated with increased use of warm handoffs, same day consultation, shared health records, and the use of behavioral health (BH) professionals for both mental health and medical issues. Family physicians, psychiatrists, and psychologists were most likely to be training residents in BHI. CONCLUSIONS: Almost half of FMR programs have colocated BH care or fully integrated BH as defined by SAMHSA. Highly integrated FMRs use a diversity of behavioral professionals and activities. Residencies currently at the collaboration stage could increase BH provider types and BHI practices to better prepare residents for practice. Residencies with full BHI may consider focusing on supporting BHI-trained residents transitioning into practice, or disseminating the model in the general primary care community.

Identifying Prevalence and Characteristics of Behavioral Health Education in Family Medicine Clerkships: A CERA Study.

BACKGROUND AND OBJECTIVES: Many patients with behavioral health disorders do not seek or receive adequate care for their conditions. Among those that do, most will receive care in a primary care setting. To best meet this need, clinicians will need to demonstrate proficiency of behavioral health skills and evidence-based practices. We sought to explore the degree to which these skills are being taught in family medicine clerkships. METHODS: The Council of Academic Family Medicine's (CAFM) Educational Research Alliance (CERA) 2016 survey of clerkship directors (CDs) was sent to 141 CDs at US and Canadian medical schools with a required family medicine run course. CDs were asked about the inclusion of behavioral health topics, tools, and techniques in the clerkship, as well as rating the importance of these items. RESULTS: Eighty-six percent of CDs completed the survey. Mood disorders (81.4%) were most frequently taught, followed by anxiety disorders (77.8%), substance use disorders (74.4%), and impulse control disorders (39.1%). Screening tools and behavioral health counseling skills were less commonly taught. CONCLUSIONS: Many behavioral health topics are not taught universally to all family medicine clerkship students. Gaps exist between what is included in current curriculum and what is recommended by the National Clerkship Curriculum for family medicine. These gaps may represent challenges for improving the care for patients with behavioral health disorders.