An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis.

INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

Comparison of Volumetric and 2D Measurements and Longitudinal Trajectories in the Response Assessment of BRAF V600E-Mutant Pediatric Gliomas in the Pacific Pediatric Neuro-Oncology Consortium Clinical Trial.

BACKGROUND AND PURPOSE: Response on imaging is widely used to evaluate treatment efficacy in clinical trials of pediatric gliomas. While conventional criteria rely on 2D measurements, volumetric analysis may provide a more comprehensive response assessment. There is sparse research on the role of volumetrics in pediatric gliomas. Our purpose was to compare 2D and volumetric analysis with the assessment of neuroradiologists using the Brain Tumor Reporting and Data System (BT-RADS) in BRAF V600E-mutant pediatric gliomas. MATERIALS AND METHODS: Manual volumetric segmentations of whole and solid tumors were compared with 2D measurements in 31 participants (292 follow-up studies) in the Pacific Pediatric Neuro-Oncology Consortium 002 trial (NCT01748149). Two neuroradiologists evaluated responses using BT-RADS. Receiver operating characteristic analysis compared classification performance of 2D and volumetrics for partial response. Agreement between volumetric and 2D mathematically modeled longitudinal trajectories for 25 participants was determined using the model-estimated time to best response. RESULTS: Of 31 participants, 20 had partial responses according to BT-RADS criteria. Receiver operating characteristic curves for the classification of partial responders at the time of first detection (median = 2 months) yielded an area under the curve of 0.84 (95% CI, 0.69-0.99) for 2D area, 0.91 (95% CI, 0.80-1.00) for whole-volume, and 0.92 (95% CI, 0.82-1.00) for solid volume change. There was no significant difference in the area under the curve between 2D and solid (P = .34) or whole volume (P = .39). There was no significant correlation in model-estimated time to best response (ρ = 0.39, P >.05) between 2D and whole-volume trajectories. Eight of the 25 participants had a difference of ≥90 days in transition from partial response to stable disease between their 2D and whole-volume modeled trajectories. CONCLUSIONS: Although there was no overall difference between volumetrics and 2D in classifying partial response assessment using BT-RADS, further prospective studies will be critical to elucidate how the observed differences in tumor 2D and volumetric trajectories affect clinical decision-making and outcomes in some individuals.

A large open access dataset of brain metastasis 3D segmentations on MRI with clinical and imaging information.

Resection and whole brain radiotherapy (WBRT) are standard treatments for brain metastases (BM) but are associated with cognitive side effects. Stereotactic radiosurgery (SRS) uses a targeted approach with less side effects than WBRT. SRS requires precise identification and delineation of BM. While artificial intelligence (AI) algorithms have been developed for this, their clinical adoption is limited due to poor model performance in the clinical setting. The limitations of algorithms are often due to the quality of datasets used for training the AI network. The purpose of this study was to create a large, heterogenous, annotated BM dataset for training and validation of AI models. We present a BM dataset of 200 patients with pretreatment T1, T1 post-contrast, T2, and FLAIR MR images. The dataset includes contrast-enhancing and necrotic 3D segmentations on T1 post-contrast and peritumoral edema 3D segmentations on FLAIR. Our dataset contains 975 contrast-enhancing lesions, many of which are sub centimeter, along with clinical and imaging information. We used a streamlined approach to database-building through a PACS-integrated segmentation workflow.

Comparison of volumetric and 2D-based response methods in the PNOC-001 pediatric low-grade glioma clinical trial.

Background: Although response in pediatric low-grade glioma (pLGG) includes volumetric assessment, more simplified 2D-based methods are often used in clinical trials. The study's purpose was to compare volumetric to 2D methods. Methods: An expert neuroradiologist performed solid and whole tumor (including cyst and edema) volumetric measurements on MR images using a PACS-based manual segmentation tool in 43 pLGG participants (213 total follow-up images) from the Pacific Pediatric Neuro-Oncology Consortium (PNOC-001) trial. Classification based on changes in volumetric and 2D measurements of solid tumor were compared to neuroradiologist visual response assessment using the Brain Tumor Reporting and Data System (BT-RADS) criteria for a subset of 65 images using receiver operating characteristic (ROC) analysis. Longitudinal modeling of solid tumor volume was used to predict BT-RADS classification in 54 of the 65 images. Results: There was a significant difference in ROC area under the curve between 3D solid tumor volume and 2D area (0.96 vs 0.78, P = .005) and between 3D solid and 3D whole volume (0.96 vs 0.84, P = .006) when classifying BT-RADS progressive disease (PD). Thresholds of 15-25% increase in 3D solid tumor volume had an 80% sensitivity in classifying BT-RADS PD included in their 95% confidence intervals. The longitudinal model of solid volume response had a sensitivity of 82% and a positive predictive value of 67% for detecting BT-RADS PD. Conclusions: Volumetric analysis of solid tumor was significantly better than 2D measurements in classifying tumor progression as determined by BT-RADS criteria and will enable more comprehensive clinical management.

Everolimus for Children With Recurrent or Progressive Low-Grade Glioma: Results From the Phase II PNOC001 Trial.

PURPOSE: The PNOC001 phase II single-arm trial sought to estimate progression-free survival (PFS) associated with everolimus therapy for progressive/recurrent pediatric low-grade glioma (pLGG) on the basis of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway activation as measured by phosphorylated-ribosomal protein S6 and to identify prognostic and predictive biomarkers. PATIENTS AND METHODS: Patients, age 3-21 years, with progressive/recurrent pLGG received everolimus orally, 5 mg/m2 once daily. Frequency of driver gene alterations was compared among independent pLGG cohorts of newly diagnosed and progressive/recurrent patients. PFS at 6 months (primary end point) and median PFS (secondary end point) were estimated for association with everolimus therapy. RESULTS: Between 2012 and 2019, 65 subjects with progressive/recurrent pLGG (median age, 9.6 years; range, 3.0-19.9; 46% female) were enrolled, with a median follow-up of 57.5 months. The 6-month PFS was 67.4% (95% CI, 60.0 to 80.0) and median PFS was 11.1 months (95% CI, 7.6 to 19.8). Hypertriglyceridemia was the most common grade ≥3 adverse event. PI3K/AKT/mTOR pathway activation did not correlate with clinical outcomes (6-month PFS, active 68.4% v nonactive 63.3%; median PFS, active 11.2 months v nonactive 11.1 months; P = .80). Rare/novel KIAA1549::BRAF fusion breakpoints were most frequent in supratentorial midline pilocytic astrocytomas, in patients with progressive/recurrent disease, and correlated with poor clinical outcomes (median PFS, rare/novel KIAA1549::BRAF fusion breakpoints 6.1 months v common KIAA1549::BRAF fusion breakpoints 16.7 months; P < .05). Multivariate analysis confirmed their independent risk factor status for disease progression in PNOC001 and other, independent cohorts. Additionally, rare pathogenic germline variants in homologous recombination genes were identified in 6.8% of PNOC001 patients. CONCLUSION: Everolimus is a well-tolerated therapy for progressive/recurrent pLGGs. Rare/novel KIAA1549::BRAF fusion breakpoints may define biomarkers for progressive disease and should be assessed in future clinical trials.

Teaching Sideways: Implementing a Peer-Led Medical Student Orientation Bootcamp and Survival Guide for Internal Medicine Clerkship.

OBJECTIVES: Transitioning from classroom learning to clerkships presents a challenge for medical students because there is often sparse preparation material on how to effectively contribute to the medical team as a clerkship student. Although some medical schools have implemented transition-to-clerkship sessions, they often are led by faculty and lack the practical and contemporary guidance from students who have recently completed clerkships themselves. METHODS: Using a sideways mentorship approach, we implemented a 1-hour near-peer Internal Medicine (IM) clerkship orientation bootcamp at our medical school and wrote an accompanying survival guide to teach students how to function as part of a medical team and to increase the transparency of student expectations and evaluations during the clerkship. The 1-hour session covered the following core topics: clerkship logistics, how to gather/present clinical information, a resident/student question-and-answer panel, and how to contribute to the medical team. A postclerkship medical student and second-year IM resident conducted the bootcamp for four student cohorts (105 students total) during the January to December 2022 clerkship year before the IM rotation of each cohort. After the bootcamp, students received a copy of the survival guide to solidify concepts covered in the session. RESULTS: A preclerkship survey included questions to assess student confidence in 10 core IM clerkship domains pre- and postbootcamp. Both pre- and postclerkship surveys asked students to provide feedback on bootcamp strengths and weaknesses. Wilcoxon signed rank tests revealed a significant increase in postbootcamp student confidence rating for all 10 clerkship domains in the early clerkship cohort and in the late clerkship cohort for all of the domains, except finding clinical reference resources (P = 0.15). The bootcamp had the largest effect size (r) on student confidence in both early and late clerkship cohorts for the following clerkship domains: familiarity with IM clerkship evaluation (early: r = 0.61, P < 0.001; late: r = 0.56, P = 0.002), identification of ways to contribute to the medical team (early: r = 0.58, P < 0.001; late: r = 0.63, P < 0.001), and prerounding/chart checking (early r = 0.52, P < 0.001; late: r = 0.55, P = 0.001). The percentage of students rating the helpfulness of both the bootcamp and survival guide as a 3 to 5 on a 5-point Likert scale in the postclerkship survey was highest for the following domains: being familiar with the structure of a subjective, objective, assessment, and plan presentation (88% and 97%), prerounding/chart checking (82% and 95%), writing progress notes (82% and 92%), and identifying ways to contribute to the medical team (82% and 95%). Students commented that the main strengths of the bootcamp included its specific tips on synthesizing and presenting clinical information and its transparency about student expectations and experiences. CONCLUSIONS: A structured student-led bootcamp can increase clerkship preparation in core domains. The bootcamp is now part of mandatory clerkship didactics at our medical school, given its success during the 2022 clerkship year, and its content is continuing to be expanded upon by postclerkship students and residents. In addition, the format of the bootcamp also is being adapted to other clerkships, including surgery and obstetrics/gynecology.

Application of novel PACS-based informatics platform to identify imaging based predictors of CDKN2A allelic status in glioblastomas.

Gliomas with CDKN2A mutations are known to have worse prognosis but imaging features of these gliomas are unknown. Our goal is to identify CDKN2A specific qualitative imaging biomarkers in glioblastomas using a new informatics workflow that enables rapid analysis of qualitative imaging features with Visually AcceSAble Rembrandtr Images (VASARI) for large datasets in PACS. Sixty nine patients undergoing GBM resection with CDKN2A status determined by whole-exome sequencing were included. GBMs on magnetic resonance images were automatically 3D segmented using deep learning algorithms incorporated within PACS. VASARI features were assessed using FHIR forms integrated within PACS. GBMs without CDKN2A alterations were significantly larger (64 vs. 30%, p = 0.007) compared to tumors with homozygous deletion (HOMDEL) and heterozygous loss (HETLOSS). Lesions larger than 8 cm were four times more likely to have no CDKN2A alteration (OR: 4.3; 95% CI 1.5-12.1; p < 0.001). We developed a novel integrated PACS informatics platform for the assessment of GBM molecular subtypes and show that tumors with HOMDEL are more likely to have radiographic evidence of pial invasion and less likely to have deep white matter invasion or subependymal invasion. These imaging features may allow noninvasive identification of CDKN2A allele status.

Evolution and implementation of radiographic response criteria in neuro-oncology.

Radiographic response assessment in neuro-oncology is critical in clinical practice and trials. Conventional criteria, such as the MacDonald and response assessment in neuro-oncology (RANO) criteria, rely on bidimensional (2D) measurements of a single tumor cross-section. Although RANO criteria are established for response assessment in clinical trials, there is a critical need to address the complexity of brain tumor treatment response with multiple new approaches being proposed. These include volumetric analysis of tumor compartments, structured MRI reporting systems like the Brain Tumor Reporting and Data System, and standardized approaches to advanced imaging techniques to distinguish tumor response from treatment effects. In this review, we discuss the strengths and limitations of different neuro-oncology response criteria and summarize current research findings on the role of novel response methods in neuro-oncology clinical trials and practice.

A Large Open Access Dataset of Brain Metastasis 3D Segmentations with Clinical and Imaging Feature Information.

Resection and whole brain radiotherapy (WBRT) are the standards of care for the treatment of patients with brain metastases (BM) but are often associated with cognitive side effects. Stereotactic radiosurgery (SRS) involves a more targeted treatment approach and has been shown to avoid the side effects associated with WBRT. However, SRS requires precise identification and delineation of BM. While many AI algorithms have been developed for this purpose, their clinical adoption has been limited due to poor model performance in the clinical setting. Major reasons for non-generalizable algorithms are the limitations in the datasets used for training the AI network. The purpose of this study was to create a large, heterogenous, annotated BM dataset for training and validation of AI models to improve generalizability. We present a BM dataset of 200 patients with pretreatment T1, T1 post-contrast, T2, and FLAIR MR images. The dataset includes contrast-enhancing and necrotic 3D segmentations on T1 post-contrast and whole tumor (including peritumoral edema) 3D segmentations on FLAIR. Our dataset contains 975 contrast-enhancing lesions, many of which are sub centimeter, along with clinical and imaging feature information. We used a streamlined approach to database-building leveraging a PACS-integrated segmentation workflow.

The Brain Tumor Segmentation (BraTS-METS) Challenge 2023: Brain Metastasis Segmentation on Pre-treatment MRI.

Clinical monitoring of metastatic disease to the brain can be a laborious and timeconsuming process, especially in cases involving multiple metastases when the assessment is performed manually. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) guideline, which utilizes the unidimensional longest diameter, is commonly used in clinical and research settings to evaluate response to therapy in patients with brain metastases. However, accurate volumetric assessment of the lesion and surrounding peri-lesional edema holds significant importance in clinical decision-making and can greatly enhance outcome prediction. The unique challenge in performing segmentations of brain metastases lies in their common occurrence as small lesions. Detection and segmentation of lesions that are smaller than 10 mm in size has not demonstrated high accuracy in prior publications. The brain metastases challenge sets itself apart from previously conducted MICCAI challenges on glioma segmentation due to the significant variability in lesion size. Unlike gliomas, which tend to be larger on presentation scans, brain metastases exhibit a wide range of sizes and tend to include small lesions. We hope that the BraTS-METS dataset and challenge will advance the field of automated brain metastasis detection and segmentation.

Ameloblastic fibrosarcoma transformation from ameloblastic fibroma.

Ameloblastic fibrosarcoma (AFS) is an extremely rare malignant odontogenic tumor. It is composed of benign odontogenic epithelium, resembling that of ameloblastoma, and a mesenchymal part exhibiting features of fibrosarcoma. The development of this lesion in the jaws is either de novo or from preexisting ameloblastic fibroma which has been well documented. The most commonly affected site within the jaw is the posterior mandible. These tumors show local aggressiveness and a high tendency to recur. We present a case of a 33-year-old female patient with swelling of the right posterior mandible for 2 months and progressive paresthesia of the same region for the past 6 months. Patient's history revealed undergoing surgical enucleation for ameloblastic fibroma before a year in the same region as current swelling. Examination of the swelling revealed an ulceroprolifeartive Growth of 6 × 4.5 cm extending from premolar to molar region. Primary investigation involved biopsy of the swelling, which was reported as sarcoma for which resection of the right hemimandible and selective neck dissection was performed. Following surgery, the final histopathology report of the resected specimen was reported to be AFS. One year after the surgical procedure, the patient is clinically and radiologically disease-free. Considering the aggressive nature of these tumors, it is vital to give an accurate diagnosis through biopsy, which is considered as gold standard diagnostic evidence, so that the surgeon plans the appropriate therapeutic decision. Knowledge of this rare entity and its histologic features as opposed to the more common benign counterparts such as ameloblastoma or ameloblastic fibroma is crucial as the latter involves a conservative treatment approach while the former can only be treated through aggressive resections.

Comparison of intraarticular injection of platelet-rich plasma following arthrocentesis, with sodium hyaluronate and conventional arthrocentesis for management of internal derangement of temporomandibular joint.

Aim: The aim of the study is to compare the efficacy of platelet-rich plasma (PRP) for the management of internal derangement of temporomandibular joint (TMJ). Settings and Design: Thirty-three patients were selected from the pool of patients visiting the department of oral and maxillofacial surgery. Simple randomization was done. Subjects and Methods: Patients with anterior disc displacement without reduction (DDWOR) were indicated for arthrocentesis. Group A patients are treated with PRP, Group B patients with sodium hyaluronate following arthrocentesis, and Group C patients were treated with arthrocentesis alone. Postoperative pain and maximal incisal opening are the primary outcomes evaluated. Statistical Analysis Used: The collected data were analyzed with IBM. SPSS statistics software 23.0 version and the one-way ANOVA with Tukey's post hoc test were used. Results: The mean age is 33 years, with female predominance. The statistical significant differences (P < 0.05) in pain and MIO between the 3 groups at the end of 3rdweek, 4thweek, and 3rd month postoperatively are seen in PRP group comparative to other groups. Conclusions: Our study has concluded that the intraarticular injection of PRP is an effective management for anterior DDWOR of TMJ than intraarticular injection of sodium hyaluronate and arthrocentesis in, reducing the pain and improving the interincisal distance in patients with DDWOR, thus providing a rapid recovery and improved quality of life.

Evaluation of effect of submucosal administration of depomedrol in management of postoperative sequelae in mandibular fractures: A randomized clinical trial study.

Introduction: The mandible is a commonly fractured bone in the face, a fact related to its prominent and exposed position. Open reduction and internal fixation (ORIF) of mandibular fractures has been associated with trauma to the surgical site and the surrounding tissues. Purpose: The purpose of this study is to evaluate the effects of immediate postoperative submucosal depomedrol administration on postoperative pain, edema, and trismus after ORIF for mandibular fractures. Materials and Methods: We conducted a prospective, randomized, controlled, double-blind study of forty patients who required ORIF for mandibular fractures under general anesthesia. The patients were divided into two groups, an experimental group who received immediate postoperative submucosal 40 mg of depomedrol injection through the surgical incision site, and a control group who did not receive any drug. Pain was assessed using a Visual Analog Scale score and the frequency of analgesic consumption at various postoperative intervals. The maximum interincisal distance and facial measurements were compared before surgery and at 24, 48, 72 h, and 7 days after surgery. Results: Statistical analysis of the data indicated a significant decrease in edema, trismus, and pain in the depomedrol group. No clinically apparent infection, disturbance of wound healing, or other corticosteroid-related complications were noted. Conclusion: The results of our study suggest that submucosal administration of depomedrol injection after ORIF for mandibular fractures is effective in reducing postoperative pain, edema, and trismus.

Impact of Cannabis Use, Substance Use Disorders, and Psychiatric Diagnoses on COVID-19 Outcomes: A Retrospective Cohort Study.

Objective: While psychiatric disorders have been recognized as a risk factor for COVID-19 outcomes, the impact of substance use disorders (SUD) on COVID-19 outcomes has not, to date, been examined in a systematic manner. We examined the association between SUD (cannabis, cocaine, alcohol, opioid, and benzodiazepine) as well as psychiatric diagnoses (schizophrenia, mood disorders, anxiety disorders) and COVID-19 outcomes in a large, retrospective cohort study.Methods: COVID-19-positive patients admitted to a large health care system in the US between January and December 2020 were included in this study. SUD and psychiatric diagnoses were identified from urine toxicology reports and ICD-10 diagnosis codes in the electronic medical record, respectively. Multivariable logistic regression was performed controlling for potential confounders such as age, race, sex, smoking status, and medical comorbidities. COVID-19-relevant outcomes included mortality, need for intensive care unit (ICU) admission, need for ventilatory support, length of hospitalization, and number of hospitalizations.Results: Among COVID-19 patients (N = 6,291), those with SUD were more likely to require ICU admission (adjusted odds ratio [AOR] = 1.46, P = .003) and ventilatory support (AOR = 1.49, P = .01). The association between SUD and ICU admission was driven by alcohol use disorder (AUD), whereas that between SUD and ventilatory support was driven by both AUD and opioid use disorder (OUD). Patients with SUD were more likely to have a longer mean maximum length of hospitalization (11.32 vs 8.62 days, P < .0001) and a greater mean number of hospital admissions in 2020 (2.96 vs 2.33, P < .0001). These associations were significant for cannabis use disorder, AUD, OUD, and benzodiazepine use disorder. The association with greater number of admissions was also significant for cocaine use disorder. Patients with psychiatric diagnoses were also more likely to have a greater maximum length of hospitalization (11.93 vs 8.39 days, P < .0001) and hospital admissions (2.72 vs 2.31, P < .0001). These associations were significant for schizophrenia, mood disorders, and anxiety disorders.Conclusions: COVID-19 patients with SUD had greater likelihood of requiring critical interventions, such as ICU admission and ventilatory support. SUD and psychiatric diagnoses were also associated with a longer duration of hospitalization and greater number of hospital admissions. These findings identify COVID-19 patients with SUD and psychiatric comorbidities as a high-risk group.

Systematic Review and Meta-analysis: An Empirical Approach to Defining Treatment Response and Remission in Pediatric Obsessive-Compulsive Disorder.

OBJECTIVE: A lack of universal definitions for response and remission in pediatric obsessive-compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes. METHOD: A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references; 42 randomized controlled clinical trials were considered eligible, and 21 provided data for inclusion (N = 1,234). Scores of ≤2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A 2-stage, random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively. RESULTS: The CY-BOCS had sufficient discriminative ability to determine response (AUC = 0.89) and remission (AUC = 0.92). The optimal cutoff for response was a ≥35% reduction from baseline to posttreatment (sensitivity = 83.9, 95% CI = 83.7-84.1; specificity = 81.7, 95% CI = 81.5-81.9). The optimal cutoff for remission was a posttreatment raw score of ≤12 (sensitivity = 82.0, 95% CI = 81.8-82.2; specificity = 84.6, 95% CI = 84.4-84.8). CONCLUSION: Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD randomized controlled clinical trials. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD.

What Does Honors Mean? National Analysis of Medical School Clinical Clerkship Grading.

OBJECTIVE: Medical Student Performance Evaluation (MSPE) letters provide critical comparative information about clerkship performance, and are a crucial part of the surgical residency application. The elimination of USMLE Step 1 numeric reporting increases the importance of transparency, standardization, and accessibility of comparative information reported on the MSPE. The objective of our study was to measure the variability in clerkship grade reporting on the MSPE from US medical schools, particularly focusing on the highest (honors) grades. DESIGN, SETTING, AND PARTICIPANTS: We identified representative MSPE letters from US medical schools and recorded the percentage of honors for 5 core clerkships. We grouped medical schools according to medical school rankings, geographic region, and number of grading categories RESULTS: Of 122 medical schools, 106 schools (87%) reported their grading scheme and percent honors. The most commonly used grading scheme was a 4-tier system (51/122; 42%). The percentage of honors was highly variable (from 1-91%) and did not vary by region. However, schools in the top 20 research ranking were less likely to report grade comparisons (30% vs. 10%), and more likely to award more students honors in 4 of the 5 clerkships. Schools in the top 20 primary care ranking were more likely to award more honors in the medicine clerkship. CONCLUSIONS: There is significant variability in the number of grading tiers used and the percentage of students awarded honors across US medical schools. Factors that correlated to higher grades included schools with higher rankings, and higher ranked schools were less likely to report comparative information at all.

Does size matter? A national analysis of the utility of induction therapy for large thymomas.

BACKGROUND: Tumor size of 8 cm or greater is a risk factor for recurrence after thymoma resection, but the role of induction therapy for large thymomas is not well defined. This study tested the hypothesis that induction therapy for thymomas 8 cm and larger improves survival. METHODS: The use of induction therapy for patients treated with surgical resection for Masaoka stage I-III thymomas in the National Cancer Database between 2006-2013 was evaluated using logistic regression, Kaplan-Meier analysis, and Cox-proportional hazards methods. RESULTS: Of the 1,849 patients who met inclusion criteria, 582 (31.5%) had tumors ≥8 cm. Five-year survival was worse in patients with tumors ≥8 cm compared to smaller tumors [84.6% (95% CI: 81.2-88.1%) vs. 89.4% (95% CI: 87.2-91.7%), P=0.003]. Induction therapy was used in 166 (9.0%) patients overall and was more likely in patients with tumors ≥8 cm [adjusted odds ratio (AOR) 3.257, P<0.001]. Induction therapy was not associated with improved survival in the subset of patients with tumors ≥8 cm in either univariate [80.9% (95% CI: 72.6-90.1%) vs. 85.4% (95% CI: 81.8-89.3%), P=0.27] or multivariable analysis [hazard ratio (HR) 1.54, P=0.10]. Increasing age (HR 1.56/decade, P<0.001) and Masaoka stage III (HR 1.76, P=0.04) were associated with worse survival in patients with tumors ≥8 cm. CONCLUSIONS: Survival after thymoma resection is worse for tumors 8 cm or larger compared to smaller tumors and is not improved by induction therapy. Size alone should not be a criterion for using induction therapy prior to thymoma resection.

Ruthenium-Catalyzed Asymmetric Allylic Alkylation of Isatins.

A new ruthenium-based catalytic system for branched-selective asymmetric allylic alkylation is disclosed and applied to the synthesis of chiral isatin derivatives. The catalyst, which is generated in situ from commercially available CpRu(MeCN)3PF6 and a BINOL-derived phosphoramidite, is both highly active (TON up to 180) and insensitive to air and moisture. Additionally, the N-alkylated isatins accessible using this methodology are versatile building blocks that are readily transformed into chiral analogs of achiral drug molecules.

Risk Factors for Withdrawal of Life-Sustaining Treatment in Severe Traumatic Brain Injury.

Studies demonstrate a significant variation in decision-making regarding withdrawal of life-sustaining treatment (WLST) practices for patients with severe traumatic brain injury (TBI). We investigated risk factors associated with WLST in severe TBI. We hypothesized age ≥65 years would be an independent risk factor. In addition, we compared survivors with patients who died in hospital after WLST to identify potential factors associated with in-hospital mortality. The Trauma Quality Improvement Program (2010-2016) was queried for patients with severe TBI of the head. Patients were compared by age (age < 65 and age ≥ 65 years) and survival after WLST (survivors versus non-survivors) at hospitalization discharge. A multivariable logistic regression model was used for analysis. From 1,403,466 trauma admissions, 328,588 (23.4%) patients had severe TBI. Age ≥ 65 years was associated with increased WLST (odds ratio: 1.76, confidence interval: 1.59-1.94, P < 0.001), whereas nonwhite race was associated with decreased WLST (odds ratio: 0.60, confidence interval: 0.55-0.65, P < 0.001). Compared with non-survivors of WLST, survivors were older (74 vs 61 years, P < 0.001) and more likely to have comorbidities such as hypertension (57% vs 38.5%, P < 0.001). Age ≥ 65 years was an independent risk factor for WLST, and nonwhite race was associated with decreased WLST. Patients surviving until discharge after WLST decision were older (≥74 years) and had multiple comorbidities.