Citations

INTRODUCTION: Eosinophilic gastritis (EG) is a chronic inflammatory disease of the stomach characterized by eosinophil-predominant gastric mucosal inflammation and gastrointestinal symptoms. The aim of this study was to prospectively evaluate endoscopic features in a large series of children and adults with EG to better understand the endoscopic manifestations and develop a standardized instrument for investigations. METHODS: Data were prospectively collected as part of the Consortium for Eosinophilic Gastrointestinal Disease Researchers, a national collaborative network. Endoscopic features were prospectively recorded using a system specifically developed for EG, the EG Endoscopic Reference System (EG-REFS). Correlations were made between EG-REFS and clinical and histologic features. RESULTS: Of 98 patients with EG, 65 underwent assessments using EG-REFS. The most common findings were erythema (72%), raised lesions (49%), erosions (46%), and granularity (35%); only 8% of patients with active histology (≥30 eosinophils/high-power field) exhibited no endoscopic findings. A strong correlation between EG-REFS scores and physician global assessment of endoscopy severity was demonstrated (Spearman r = 0.84, P < 0.0001). The overall score and specific components of EG-REFS were more common in the antrum than in the fundus or body. EG-REFS severity was significantly correlated with active histology, defined by a threshold of ≥30 eosinophils/high-power field ( P = 0.0002). DISCUSSION: Prospective application of EG-REFS identified gastric features with a strong correlation with physician global assessment of endoscopic activity in EG. Endoscopic features demonstrated greater severity in patients with active histology and a predilection for the gastric antrum. Further development of EG-REFS should improve its utility in clinical studies.

Abstract ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1623 endometriosis‐associated ovarian carcinomas, including 1078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas, through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8 + tumour‐infiltrating lymphocytes (CD8 + TILs), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOCs and 25% of ENOCs. We found no associations between ARID1A loss and outcomes, stage, age, or CD8 + TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients ( p = 0.012) and was associated with MMRd ( p < 0.001) and the presence of CD8 + TILs ( p = 0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOCs we also observed an association with ARID1A loss‐of‐function mutation as a result of small indels ( p = 0.035, versus single nucleotide variants). In ENOC, the association with ARID1A loss, CD8 + TILs, and age appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8 + TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss‐of‐function mutations in endometriosis‐associated ovarian cancers and brings clarity to the prognostic significance. © 2021 The Pathological Society of Great Britain and Ireland.

BackgroundDecision aids (DAs) can improve knowledge for prostate cancer treatment. However, the relative effects of DAs delivered within the clinical encounter and in more diverse patient populations are unknown. A multicenter cluster randomized controlled trial with a 2×2 factorial design was performed to test the effectiveness of within‐visit and previsit DAs for localized prostate cancer, and minority men were oversampled.MethodsThe interventions were delivered in urology practices affiliated with the NCI Community Oncology Research Program Alliance Research Base. The primary outcome was prostate cancer knowledge (percent correct on a 12‐item measure) assessed immediately after a urology consultation.ResultsFour sites administered the previsit DA (39 patients), 4 sites administered the within‐visit DA (44 patients), 3 sites administered both previsit and within‐visit DAs (25 patients), and 4 sites provided usual care (50 patients). The median percent correct in prostate cancer knowledge, based on the postvisit knowledge assessment after the intervention delivery, was as follows: 75% for the pre+within‐visit DA study arm, 67% for the previsit DA only arm, 58% for the within‐visit DA only arm, and 58% for the usual‐care arm. Neither the previsit DA nor the within‐visit DA had a significant impact on patient knowledge of prostate cancer treatments at the prespecified 2.5% significance level (P = .132 and P = .977, respectively).ConclusionsDAs for localized prostate cancer treatment provided at 2 different points in the care continuum in a trial that oversampled minority men did not confer measurable gains in prostate cancer knowledge.

Abstract Background Lyme disease, the most common tickborne disease in the United States, may be prevented by taking a single 200-mg dose of oral doxycycline after a high-risk bite from a blacklegged tick. Currently, it is not known how Lyme disease post-exposure prophylaxis (PEP) might vary by region and healthcare system. We identified single-dose doxycycline medication orders in three healthcare systems in states with high incidence of Lyme disease and compared associated patient and provider characteristics. Methods Electronic health record data during 2012 – 2016 were obtained from three healthcare systems: Geisinger (Pennsylvania), Marshfield Clinic (Wisconsin), and Mayo Clinic (Minnesota/Wisconsin). Creation of analytic variables and analysis were harmonized across the three sites. Medication orders for single-dose doxycycline ≤200 mg that were accompanied by specific key words or diagnostic codes (e.g., tick bite; Lyme disease prevention) were considered evidence of PEP. Manual chart review was performed from a random subset to evaluate the algorithms used to identify PEP. Results Among 2,937,585 patients with at least one medication order or clinical encounter during the study period, 14,102 single-dose doxycycline orders for Lyme disease PEP for 13,172 unique patients were identified. The typical patient receiving PEP was older (mean age 51 – 58 years), male (56 – 59%), and non-Hispanic White (81 – 98%). The annual seasonality of medication orders was bimodal, with peaks occurring during April – July and October – November. The most common encounter setting was an outpatient clinic or urgent care center (80 – 91%); medication orders after patient phone calls in the absence of an in-person visit occurred frequently (14 – 19%) in two health systems. Chart abstractions (n=600) revealed instances of PEP prescribed inappropriately (e.g., bite from a non-blacklegged tick; patient with symptoms of acute Lyme disease). Conclusion Lyme disease PEP with a single dose of doxycycline was frequently prescribed in healthcare systems where there is a high incidence of Lyme disease. PEP was most commonly prescribed to non-Hispanic Whites over the age of 50 years. Public health initiatives for tickborne disease prevention should include clinician education on the appropriate use of Lyme disease PEP. Disclosures Anna M. Schotthoefer, PhD, HelixBind (Other Financial or Material Support, salary support) John Zeuli, PharmD, INSMED (Other Financial or Material Support, honoraria for educational speaking)

Purpose To develop and internally validate a machine‐learning algorithm to reliably predict cost after anterior cruciate ligament reconstruction (ACLR). Methods A retrospective review of the New York State Ambulatory Surgery and Services database was performed to identify patients who underwent elective ACLR from 2015 to 2016. Features included in initial models consisted of patient characteristics (age, sex, insurance status, income, medical comorbidities as classified by the Clinical Classifications Software diagnosis code) as well as intraoperative variables (type of anesthesia and procedure‐specific factors). Models were generated to predict total charges using 4 algorithms: random forest, extreme gradient boost, elastic net penalized regression, and support vector machines with radial kernels. Training was performed with 10‐fold cross‐validation followed by internal validation via 0.632 bootstrapping. Model discriminative performance was assessed by area under the receiver operating characteristic curve, calibration, and the Brier score. Decision curve analysis was performed to demonstrate the net benefit of using the final model in practice. Results In total, 7,311 patients undergoing ambulatory ACLR were included. The random forest model demonstrated the best performance assessed via internal validation (area under the curve = 0.85), calibration, and the Brier score (0.208). Cost incurred was influenced by anesthesia type, operating room time, and number of chronic comorbidities. Decision curve analysis revealed a net benefit for use of the random forest model and the model was integrated into a web‐based open‐access application. Conclusions The random forest model predicted cost after ambulatory ACLR using a large, statewide database with good performance. The top variables found to predict increased charges were general anesthesia, operating room time, meniscal repair, self‐pay insurance, patient neighborhood characteristics, and number of chronic conditions. Level of Evidence III, retrospective cohort study.

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

Over the past few years, the NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways for treatment of microscopic satellitosis (added in v2.2020), and the following Principles sections: Molecular Testing (added in v2.2019), Systemic Therapy Considerations (added in v2.2020), and Brain Metastases Management (added in v3.2020). The v1.2021 update included additional modifications of these sections and notable revisions to Principles of: Pathology, Surgical Margins for Wide Excision of Primary Melanoma, Sentinel Lymph Node Biopsy, Completion/Therapeutic Lymph Node Dissection, and Radiation Therapy. These NCCN Guidelines Insights discuss the important changes to pathology and surgery recommendations, as well as additions to systemic therapy options for patients with advanced disease.

INTRODUCTION: The optimal instrument for assessing histologic disease activity in patients with eosinophilic esophagitis (EoE) is unclear. We assessed the responsiveness of the EoE Histologic Scoring System (EoE-HSS) when compared with that of the peak eosinophil count (PEC). METHODS: Histopathology slides were obtained from patients with EoE at baseline and after 8 weeks of treatment with swallowed topical budesonide or elimination diet. Two blinded gastrointestinal pathologists scored biopsies on the EoE-HSS, PEC, and 100-mm visual analog scale (VAS) of overall histologic severity. Change was defined as an improvement by ≥0.5 SD in baseline VAS. Responsiveness was quantified using the standardized effect size (SES) and the probability that the index distinguishes a patient with improvement from a patient without improvement, which is the area under the receiver operating characteristic curve (AUC). Longitudinal validity was assessed using Pearson correlations between changes in EoE-HSS and both PEC and VAS. RESULTS: The EoE-HSS grade (SES 2.18 [95% confidence interval, CI: 1.46–2.88]; AUC 0.73 [95% CI: 0.57–0.84]) and stage (SES 2.07 [95% CI: 1.37–2.77]; AUC 0.73 [95% CI: 0.58–0.84]) were highly responsive, similar to PEC (SES 1.44 [95% CI: 0.80–2.07]; AUC 0.73 [95% CI: 0.58–0.84]). The EoE-HSS grade and stage were more highly correlated with changes in VAS (grade 0.92 [95% CI: 0.86–0.95]; stage 0.89 [95% CI: 0.81–0.94]) than with changes in PEC (grade 0.74 [95% CI: 0.58–0.85]; stage 0.66 [95% CI: 0.47–0.80]). DISCUSSION: The EoE-HSS is highly responsive, performs similarly to PEC, and is better correlated with changes in overall histologic activity in patients with EoE.

Background: Although lower back injuries (LBIs) are common among National Collegiate Athletic Association (NCAA) female volleyball athletes, their incidence and etiology has not been well-defined. Purpose: To describe the epidemiology of LBIs in collegiate female volleyball athletes over a 5-year period from the academic years 2009 to 2010 and 2013 to 2014. Study Design: Descriptive epidemiology study. Methods: The incidence and characteristics of spine injuries were identified utilizing the NCAA Injury Surveillance Program database. Rates of injury were calculated as the number of injuries by the total number of athlete-exposures (AEs). AEs were defined as any student participation in any single NCAA-sanctioned practice or competition. The injury rate was computed as the number of injuries per the total number of AEs and reported as a ration of injuries per 10,000 exposures. The ratio was then reported as overall number as well as stratified for event, time of season, and athletic NCAA division. Incidence rate ratios were then calculated to compare rates between event type. Results with 95% CIs that did not include 1.0 were considered statistically significant. Results: An estimated 3384 LBIs occurred in NCAA female volleyball players during this 5-year time frame. These LBIs occurred at a rate of 4.89 injuries per 10,000 AEs. LBIs were 2.76 times more likely in preseason when compared with regular season. More injuries occurred in practice (85%) when compared with competition (15%). The outside hitter and middle blocker were the most commonly position to sustain an LBI. Almost 70% of injuries were new injuries, and another 29% were recurrent injuries. The most common mechanism of injury was equally split between contact (50.4%) and overuse (45.5%) injuries, whereas the remaining mechanisms of injury were secondary for unknown reasons (4.14%). Most players returned to play within 24 hours (72.3%) followed by 1 to 6 days (16.4%), and finally 7 to 12 days (11.3%). No patient required surgical intervention. Conclusion: The rate of LBIs was high (4.89/10,000 AEs) and injuries commonly recurred (29.2%). Most injuries were new, with most athletes returning to play with 24 hours.