De Novo Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression.

p16 is a tumor suppressor encoded by the CDKN2A gene whose expression is lost in approximately 50% of all human cancers. In its canonical role, p16 inhibits the G1-S-phase cell cycle progression through suppression of cyclin-dependent kinases. Interestingly, p16 also has roles in metabolic reprogramming, and we previously published that loss of p16 promotes nucleotide synthesis via the pentose phosphate pathway. However, the broader impact of p16/CDKN2A loss on other nucleotide metabolic pathways and potential therapeutic targets remains unexplored. Using CRISPR knockout libraries in isogenic human and mouse melanoma cell lines, we determined several nucleotide metabolism genes essential for the survival of cells with loss of p16/CDKN2A. Consistently, many of these genes are upregulated in melanoma cells with p16 knockdown or endogenously low CDKN2A expression. We determined that cells with low p16/CDKN2A expression are sensitive to multiple inhibitors of de novo purine synthesis, including antifolates. Finally, tumors with p16 knockdown were more sensitive to the antifolate methotrexate in vivo than control tumors. Together, our data provide evidence to reevaluate the utility of these drugs in patients with p16/CDKN2Alow tumors as loss of p16/CDKN2A may provide a therapeutic window for these agents. SIGNIFICANCE: Antimetabolites were the first chemotherapies, yet many have failed in the clinic due to toxicity and poor patient selection. Our data suggest that p16 loss provides a therapeutic window to kill cancer cells with widely-used antifolates with relatively little toxicity.

What do infectious disease specialists think about managing long COVID?

This survey of infectious disease providers on long COVID care revealed a lack of familiarity with existing resources, a sentiment of missing guidelines, and scarcity of dedicated care centers. The low response rate suggests that infectious disease specialists do not consider themselves as the primary providers of long COVID care.

Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma.

Acral melanoma (AM) has distinct characteristics as compared with cutaneous melanoma and exhibits poor response to immune checkpoint inhibitors (ICIs). Tumor-intrinsic mechanisms of immune exclusion have been identified in many cancers but less studied in AM. We characterized clinically annotated tumors from patients diagnosed with AM at our institution in correlation with ICI response using whole transcriptome RNAseq, whole exome sequencing, CD8 immunohistochemistry, and multispectral immunofluorescence imaging. A defined interferon-γ-associated T cell-inflamed gene signature was used to categorize tumors into non-T cell-inflamed and T cell-inflamed phenotypes. In combination with AM tumors from two published studies, we systematically assessed the immune landscape of AM and detected differential gene expression and pathway activation in a non-T cell-inflamed tumor microenvironment (TME). Two single-cell(sc) RNAseq AM cohorts and 11 bulk RNAseq cohorts of various tumor types were used for independent validation on pathways associated with lack of ICI response. In total, 892 specimens were included in this study. 72.5% of AM tumors showed low expression of the T cell-inflamed gene signature, with 23.9% of total tumors categorized as the non-T cell-inflamed phenotype. Patients of low CD3+CD8+PD1+ intratumoral T cell density showed poor prognosis. We identified 11 oncogenic pathways significantly upregulated in non-T cell-inflamed relative to T cell-inflamed TME shared across all three acral cohorts (MYC, HGF, MITF, VEGF, EGFR, SP1, ERBB2, TFEB, SREBF1, SOX2, and CCND1). scRNAseq analysis revealed that tumor cell-expressing pathway scores were significantly higher in low versus high T cell-infiltrated AM tumors. We further demonstrated that the 11 pathways were enriched in ICI non-responders compared with responders across cancers, including AM, cutaneous melanoma, triple-negative breast cancer, and non-small cell lung cancer. Pathway activation was associated with low expression of interferon stimulated genes, suggesting suppression of antigen presentation. Across the 11 pathways, fatty acid synthase and CXCL8 were unifying downstream target molecules suggesting potential nodes for therapeutic intervention. A unique set of pathways is associated with immune exclusion and ICI resistance in AM. These data may inform immunotherapy combinations for immediate clinical translation.

Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma.

Background: Acral melanoma (AM) has distinct characteristics as compared to cutaneous melanoma and exhibits poor response to immune checkpoint inhibitors (ICI). Tumor-intrinsic mechanisms of immune exclusion have been identified in many cancers but less studied in AM. Methods: We characterized clinically annotated tumors from patients diagnosed with AM at our institution in correlation with ICI response using whole transcriptome RNAseq, whole exome sequencing, CD8 immunohistochemistry, and multispectral immunofluorescence imaging. A defined interferon-γ-associated T cell-inflamed gene signature was used to categorize tumors into non-T cell-inflamed and T cell-inflamed phenotypes. In combination with AM tumors from two published studies, we systematically assessed the immune landscape of AM and detected differential gene expression and pathway activation in a non-T cell-inflamed tumor microenvironment (TME). Two single-cell(sc) RNAseq AM cohorts and 11 bulk RNAseq cohorts of various tumor types were used for independent validation on pathways associated with lack of ICI response. In total, 892 specimens were included in this study. Results: 72.5% of AM tumors showed low expression of the T cell-inflamed gene signature, with 23.9% of total tumors categorized as the non-T cell-inflamed phenotype. Patients of low CD3 + CD8 + PD1 + intratumoral T cell density showed poor prognosis. We identified 11 oncogenic pathways significantly upregulated in non-T cell-inflamed relative to T cell-inflamed TME shared across all three acral cohorts (MYC, HGF, MITF, VEGF, EGFR, SP1, ERBB2, TFEB, SREBF1, SOX2, and CCND1). scRNAseq analysis revealed that tumor cell-expressing pathway scores were significantly higher in low vs high T cell-infiltrated AM tumors. We further demonstrated that the 11 pathways were enriched in ICI non-responders compared to responders across cancers, including acral melanoma, cutaneous melanoma, triple-negative breast cancer, and non-small cell lung cancer. Pathway activation was associated with low expression of interferon stimulated genes, suggesting suppression of antigen presentation. Across the 11 pathways, fatty acid synthase and CXCL8 were unifying downstream target molecules suggesting potential nodes for therapeutic intervention. Conclusions: A unique set of pathways is associated with immune exclusion and ICI resistance in AM. These data may inform immunotherapy combinations for immediate clinical translation.

De novo purine metabolism is a metabolic vulnerability of cancers with low p16 expression.

p16 is a tumor suppressor encoded by the CDKN2A gene whose expression is lost in ~50% of all human cancers. In its canonical role, p16 inhibits the G1-S phase cell cycle progression through suppression of cyclin dependent kinases. Interestingly, p16 also has roles in metabolic reprogramming, and we previously published that loss of p16 promotes nucleotide synthesis via the pentose phosphate pathway. Whether other nucleotide metabolic genes and pathways are affected by p16/CDKN2A loss and if these can be specifically targeted in p16/CDKN2A-low tumors has not been previously explored. Using CRISPR KO libraries in multiple isogenic human and mouse melanoma cell lines, we determined that many nucleotide metabolism genes are negatively enriched in p16/CDKN2A knockdown cells compared to controls. Indeed, many of the genes that are required for survival in the context of low p16/CDKN2A expression based on our CRISPR screens are upregulated in p16 knockdown melanoma cells and those with endogenously low CDKN2A expression. We determined that cells with low p16/Cdkn2a expression are sensitive to multiple inhibitors of de novo purine synthesis, including anti-folates. Tumors with p16 knockdown were more sensitive to the anti-folate methotrexate in vivo than control tumors. Together, our data provide evidence to reevaluate the utility of these drugs in patients with p16/CDKN2A-low tumors as loss of p16/CDKN2A may provide a therapeutic window for these agents.

Post COVID-19 syndrome with impairment of flow-mediated epicardial vasodilation and flow reserve.

AIMS: The aim of this study is to evaluate whether post-acute sequelae of COVID-19 cardiovascular syndrome (PASC-CVS) is associated with alterations in coronary circulatory function. MATERIALS AND METHODS: In individuals with PASC-CVS but without known cardiovascular risk factors (n = 23) and in healthy controls (CON, n = 23), myocardial blood flow (MBF) was assessed with 13 N-ammonia and PET/CT in mL/g/min during regadenoson-stimulated hyperemia, at rest, and the global myocardial flow reserve (MFR) was calculated. MBF was also measured in the mid and mid-distal myocardium of the left ventricle (LV). The Δ longitudinal MBF gradient (hyperemia minus rest) as a reflection of an impairment of flow-mediated epicardial vasodilation, was calculated. RESULTS: Resting MBF was significantly higher in PASC-CVS than in CON (1.29 ± 0.27 vs. 1.08 ± 0.20 ml/g/min, p ≤ .024), while hyperemic MBFs did not differ significantly among groups (2.46 ± 0.53 and 2.40 ± 0.34 ml/g/min, p = .621). The MFR was significantly less in PASC-CVS than in CON (1.97 ± 0.54 vs. 2.27 ± 0.43, p ≤ .031). In addition, there was a Δ longitudinal MBF gradient in PASC-CVS, not observed in CON (-0.17 ± 0.18 vs. 0.04 ± 0.11 ml/g/min, p < .0001). CONCLUSIONS: Post-acute sequelae of COVID-19 cardiovascular syndrome may be associated with an impairment of flow-mediated epicardial vasodilation, while reductions in coronary vasodilator capacity appear predominantly related to increases in resting flow in women deserving further investigations.

Leadership Experiences of Internal Medicine Residents: A Needs Assessment for Leadership Curricula.

Purpose: Leadership development during medical training is critical. Accrediting bodies strongly recommend and residents desire leadership training. However, limited needs assessment data exist regarding trainee perceptions of and experiences with leadership training. Our objective is to describe residents' perceptions of leadership and desires for leadership training with the goal of informing effective curricular development. Patients and Methods: In 2019 a trained qualitative interviewer conducted semi-structured interviews with volunteer second-year categorical internal medicine residents recruited via email across four institutions. Interviews were audio-recorded, transcribed, and inductively coded by two independent coders. After adjudicating discrepancies, coders synthesized codes into broader themes. Final thematic analysis was triangulated with the entire author group. Results: Fourteen residents were interviewed (50% female). Few reported prior leadership training. Thematic analysis yielded six main themes. First, residents perceive "leadership" to be related to formal, assigned, hierarchical roles. Second, residents identify their own leadership primarily in the inpatient clinical setting. Third, residents identify clinical competence, emotional intelligence, and communication as important skills for effective leadership. Fourth, residents struggle to identify where leadership is currently being taught. Fifth, residents desire additional leadership development. Finally, residents prefer well-labeled, interactive methods for leadership development. Conclusion: Although residents desire leadership development, these skills are not often explicitly taught, labeled, or assessed. Curriculum developers may consider explicitly contextualizing leadership training within an "everyday leadership" framework, dovetailing leadership coaching with daily teaching workflow and feedback structures, and implementing faculty development initiatives to allow for appropriate feedback and assessment of these skills.

Molecular characterization of pleomorphic mesothelioma: a multi-institutional study.

The molecular alterations of pleomorphic mesotheliomas are largely unknown. In the present study, we performed whole-exome sequencing (WES) on 24 pleomorphic mesotheliomas in order to better characterize the molecular profile of this rare histologic variant. BAP1 protein expression and CDKN2A deletion by FISH were also evaluated. Significantly mutated genes included BAP1 (35%), NF2 (13%), LATS2 (8%), TP53 (5%), and LATS1 (3%). BAP1 alterations most frequently co-occurred with deletions of chromosomes 4, 9, and 13. Other important genetic alterations in pleomorphic mesotheliomas included truncating mutations in NF2 (3 of 24; 12.5%), LATS2 (2 of 24; 8%), TP53 (1 of 24; 4%), and PBRM1 (1 of 24; 4%). Focal losses of chromosome 9p21 were most common copy number alterations (11 of 24 cases; 46%), and were assessed by WES and targeted FISH. The second most common were deletions of chromosome 4 (8 of 24; 33% pleomorphic mesotheliomas). Three cases of pleomorphic mesothelioma did not show any mutations, copy number alterations, or LOH. This first WES analysis of pleomorphic mesotheliomas did not identify novel or unique mutations. In contrast to transitional mesothelioma that was reclassified as sarcomatoid variant based on transcriptome data, pleomorphic mesotheliomas are molecularly heterogeneous and therefore their reclassification into single subtype is more difficult.

Whole exome sequencing reveals BAP1 somatic abnormalities in mesothelioma in situ.

OBJECTIVES: We have recently described the first cases of mesothelioma in situ, identified as a pure surface population of mesothelial cells that have lost BAP1 nuclear staining, in the setting of no clinically/radiologically demonstrable mesothelial tumor. These cases have a high propensity to develop invasive mesothelioma. The genetic events that lead to the development of mesothelioma in situ are unknown, nor is it known whether mesothelioma in situ cases carry somatic or germline mutations. MATERIAL AND METHODS: Whole exome sequencing (WES) was performed on two cases of mesothelioma in situ (1 pleural, 1 peritoneal) and paired formalin fixed paraffin embedded normal tissue to characterize driver mutations and copy number alterations. RESULTS: The analysis demonstrated somatic alterations in the BAP1 gene only. The pleural mesothelioma in situ showed copy number loss and LOH in the BAP1 locus on chromosome 3. The peritoneal mesothelioma in situ showed both a BAP1 somatic splice site mutation involving intron 5-exon 6 boundary (A126_splice) with an allelic fraction of 10%, and BAP1 copy number loss. No other driver point mutations, indels or somatic DNA copy number alterations reported to occur in invasive mesothelioma, or novel genetic alterations, were identified. CONCLUSION: Whole exome sequencing confirms that mesothelioma in situ development is associated with BAP1 somatic mutations/deletions, and suggests that BAP1 mutation/deletion represents a very early event in the development of malignant mesothelioma. Whether BAP1 mutation/deletion alone is sufficient to lead to invasive mesothelioma or whether additional genetic alterations are required remains to be determined.

Wellness and Work: Mixed Messages in Residency Training.

Resident physicians are at higher risk for depression, anxiety, and burnout when compared with same-age peers, resulting in substantive personal and professional consequences. Training programs across the country have acknowledged the gravity of this situation and many have implemented programs and curricula that address wellness and resilience, yet the benefits of such initiatives are still largely unknown. While the development of wellness programming is well intentioned, it is often incongruent with the residency training environment. The mixed messaging that occurs when wellness programs are implemented in environments that do not support self-care may unintentionally cause resident distress. Indeed, outside of the time dedicated to wellness curricula, residents are often rewarded for self-sacrifice. In this commentary, we describe how the complexities of the medical system and culture contribute to mixed messaging and we explore the potential impact on residents. We offer recommendations to strengthen wellness programs through efforts to promote structural change in the training environment.

Culturally Adapted Mobile Technology Improves Environmental Health Literacy in Laurentian, Great Lakes Native Americans (Anishinaabeg).

The presence of persistent bioaccumulative toxics (PBT) in aquatic food chains complicates decision processes of people with a strong culture of fish consumption. This environmental contamination is especially problematic for Native American populations in the Laurentian Great Lakes region (Anishinaabeg). Pursuing the growing discipline of environmental health literacy (EHL) may help reduce toxic exposures, support healthy decision-making, and combat health deficits. Our goals for this research were first to improve environmental health literacy using novel technologies and second to help define environmental health literacy metrics that can be tracked over time, especially regarding culturally-contextualized health interests. We recently reported that a mobile app (Gigiigoo'inaan App) presenting personalized, culturally-contextualized fish consumption advice may improve EHL for the Anishinaabeg. Gigiigoo'inaan App safely supports desired fish consumption rates by putting local data into the hands of the Anishinaabeg. We conducted a pre-test post-test evaluation with 103 Aninishinaabe adults. Participants estimated their current fish meal consumption over a hypothetical month before exposure to the software and then planned their future consumption of fish meals in a month after using the mobile app. Significantly more monthly traditional fish meals on average (Median: 4 vs 2, p=0.0005) were selected when using the app versus pre-exposure to the app. Significantly more traditional grams of fish were also selected during use of the app relative to the pretest (Median: 680.39g vs 453.59g, p=0.0007). These increases were accompanied by widespread (97%) adherence to conventional advice that minimizes PBT exposure health effects (ATSDR minimum risk levels).

Whole-exome sequencing identifies unique mutations and copy number losses in calcifying fibrous tumor of the pleura: report of 3 cases and review of the literature.

Calcifying fibrous tumor of the pleura (CFTP) is a rare mesenchymal tumor of unknown pathogenesis. The diagnosis often requires exclusion of other common entities. Our aim was to determine if genomic changes were associated with CFTP that could contribute to mechanisms underlying tumorigenesis. Three cases of CFTP with their corresponding uninvolved control lung tissue were identified. Two patients were male, and 1 was female (age range, 21-32 years). Tumors were multifocal in 2 cases and solitary in 1. Immunohistochemistry for STAT6, BCL-2, CD34, cytokeratin AE1/AE3, calretinin, desmin, S100, ALK, and ß-catenin was used. All immunohistochemistries were negative in CFTPs. DNA was isolated from all 3 pairs of CFTPs and matching normal lungs for whole-exome sequencing. Damaging, tumor-specific, coding variants were identified in 3 genes including multiple heterozygotic, de novo mutations in the Zinc Finger Protein 717 (ZNF717), fascioscapulohumeral muscular dystrophy-1 (FRG1) and cell division cycle 27 (CDC27) genes. Whole-exome sequencing revealed statistically significant, focal, tumor-specific copy number losses among all CFTPs including a large (302 kb) loss at 6p22.2 comprising 32 genes of the histone cluster 1 family and the hemochromatosis (HFE) gene. This is the first study to evaluate the molecular pathogenesis of CFTP and to identify novel deleterious mutations in ZN717, FRG1, and CDC27 genes as well as significant copy number losses on 8 chromosomes with a large loss common to all samples on chromosome 6. These mutations deleteriously altered coding domains in a manner predicted to be damaging to protein function and may contribute to CFTP tumorigenesis.

Loss of Chromatin-Remodeling Proteins and/or CDKN2A Associates With Metastasis of Pancreatic Neuroendocrine Tumors and Reduced Patient Survival Times.

Despite prognostic grading and staging systems, it is a challenge to predict outcomes for patients with pancreatic neuroendocrine tumors (PanNETs). Sequencing studies of PanNETs have identified alterations in death domain-associated protein (DAXX) and alpha-thalassemia/mental retardation X-linked chromatin remodeler (ATRX). In tumors, mutations in DAXX or ATRX and corresponding loss of protein expression correlate with shorter times of disease-free survival and disease-specific survival of patients. However, DAXX or ATRX proteins were lost in only 50% of distant metastases analyzed. We performed whole-exome sequencing analyses of 20 distant metastases from 20 patients with a single nonsyndrome, nonfunctional PanNET. We found distant metastases contained alterations in multiple endocrine neoplasia type 1 (MEN1) (n = 8), ATRX (n = 5), DAXX (n = 5), TSC2 (n = 3), and DEP domain containing 5 (DEPDC5) (n = 3). We found copy number loss of cyclin dependent kinase inhibitor 2A (CDKN2A) in 15 metastases (75%) and alterations in genes that regulate chromatin remodeling, including set domain containing 2 (SETD2) (n = 4), AT-rich interaction domain 1A (ARID1A) (n = 2), chromodomain helicase DNA binding protein 8 (CHD8) (n = 2), and DNA methyl transferase 1 (DNMT1) (n = 2). In a separate analysis of 347 primary PanNETs, we found loss or deletion of DAXX and ATRX, disruption of SETD2 function (based on loss of H3 lysine 36 trimethylation), loss of ARID1A expression or deletions in CDKN2A in 81% of primary PanNETs with distant metastases. Among patients with loss or deletion of at least 1 of these proteins or genes, 39% survived disease-free for 5 years and 44% had disease-specific survival times of 10 years. Among patients without any of these alterations, 98% survived disease-free for 5 years and 95% had disease-specific survival times of 10 years. Therefore, primary PanNETs with loss of DAXX, ATRX, H3 lysine 36 trimethylation, ARID1A, and/or CDKN2A associate with shorter survival times of patients. Our findings indicate that alterations in chromatin-remodeling genes and CDKN2A contribute to metastasis of PanNETs.

Electronic-clinical evaluation exercise (e-CEX): A new patient-centered EHR use tool.

INTRODUCTION: Electronic Health Record (EHR) use can enhance or weaken patient-provider communication. Despite EHR adoption, no validated tool exists to assess EHR communication skills. We aimed to develop and validate such a tool. METHODS: Electronic-Clinical Evaluation Exercise (e-CEX) is a 10-item-tool based on systematic literature review and pilot-testing. Second-year (MS2s) students participated in an EHR-use lecture and structured Clinical Examination (OSCE). Untrained third-year students (MS3s) participated in the same OSCE. OSCEs were scored with e-CEX compared to a standardized patient (SP) tool. Internal consistency, discriminant validity, and concurrent validity were analyzed. RESULTS: Three investigators used e-CEX to rate 70 videos (20 MS2, 50 MS3). Reliability testing indicated high internal consistency (Cronbach's alpha=0.89). MS2s scored significantly higher than untrained MS3s on e-CEX [e-CEX 55(10.7) vs. 44.9 (12.7), P=0.003], providing evidence of discriminant validity. e-CEX and SP score correlation was high (Pearson correlation=0.74, P<0.001), providing concurrent validity evidence. Item reduction suggested a three-item tool had similar explanatory power (R-squared=0.85 vs 0.86). CONCLUSION: e-CEX is a reliable, valid tool to assess medical student patient-centered EHR communication skills. PRACTICE IMPLICATIONS: While validation is needed with other healthcare providers, e-CEX may help improve provider behaviors and enhance patients' overall experience of EHR use in their care.

Abstracts From the Proceedings of the 2015 Annual Meeting of the Clerkship Directors of Internal Medicine (CDIM).

Since its inception in 1989, Clerkship Directors in Internal Medicine (CDIM) has promoted excellence in medical student education. CDIM members move medical education forward by sharing innovations in curriculum and assessment and discoveries related to educating our students and administering our programs. The Alliance for Academic Internal Medicine, of which CDIM is a founding member, broadens the umbrella beyond student education to include five academically focused specialty organizations representing departments of medicine, teaching hospitals, and medical schools working together to advance learning, discovery, and caring. CDIM held its 2015 annual meeting at Academic Internal Medicine Week in Atlanta, Georgia. This year 36 innovation and research submissions were selected for either oral abstract or poster presentation. The quality of the presentations was outstanding this year and included many of the most important issues in medical education. The CDIM research committee selected the following seven abstracts as being of the highest quality, the most generalizable, and relevant to the readership of Teaching and Learning in Medicine. Two abstracts include information from the CDIM annual survey, which remains a rich source for answering questions about student education on a national level. Looking at trends in medical education, three of the seven selected abstracts mention entrustable professional activities. Three of the abstracts address how we assess student skill and provide them with appropriate feedback. These include two schools' approach to bringing milestones into the medical student realm, use of objective structured clinical exam for assessing clinical skill in clerkship, and what students want in terms of feedback. Four articles deal with curricular innovation. These include interprofessional education, high-value care, transitions of care, and internship preparation. We are pleased to share these abstracts, which represent the breadth and quality of thought of our CDIM members.

Impact of Electronic Medical Record Use on the Patient-Doctor Relationship and Communication: A Systematic Review.

BACKGROUND: While Electronic Medical Record (EMR) use has increased dramatically, the EMR's impact on the patient-doctor relationship remains unclear. This systematic literature review sought to understand the impact of EMR use on patient-doctor relationships and communication. METHODS: Parallel searches in Ovid MEDLINE, PubMed, Scopus, PsycINFO, Cochrane Library, reference review of prior systematic reviews, meeting abstract reviews, and expert reviews from August 2013 to March 2015 were conducted. Medical Subject Heading terms related to EMR use were combined with keyword terms identifying face-to-face patient-doctor communication. English language observational or interventional studies (1995-2015) were included. Studies examining physician attitudes only were excluded. Structured data extraction compared study population, design, data collection method, and outcomes. RESULTS: Fifty-three of 7445 studies reviewed met inclusion criteria. Included studies used behavioral analysis (28) to objectively measure communication behaviors using video or direct observation and pre-post or cross-sectional surveys to examine patient perceptions (25). Objective studies reported EMR communication behaviors that were both potentially negative (i.e., interrupted speech, low rates of screen sharing) and positive (i.e., facilitating questions). Studies examining overall patient perceptions of satisfaction, communication or the patient-doctor relationship (n = 22) reported no change with EMR use (16); a positive impact (5) or showed mixed results (1). Study quality was not assessable. Small sample sizes limited generalizability. Publication bias may limit findings. DISCUSSION: Despite objective evidence that EMR use may negatively impact patient-doctor communication, studies examining patient perceptions found no change in patient satisfaction or patient-doctor communication. Therefore, our findings should encourage providers to adopt the EMR as a communication tool. Future research is needed to better understand how to enhance patient-doctor- EMR communication. This research should correlate observed physician behavior to patient satisfaction, focus on physician communication skills training, and explore inpatient experiences.

Preventing Breakdowns in Communication: Teaching Patient-Centered Posthospital Care Transitions to Medical Students.

INTRODUCTION: Patient-centered discharge care is critical to teach in clerkships: Studies have shown that patient-centered discharge care may reduce rehospitalization rates as well as ensure patient understanding after discharge. While these skills are necessary to be a successful intern, this is infrequently taught formally in clerkships. This session introduces medical students to challenges patients and providers face during care transitions, specifically, the transition after discharge from an inpatient hospital stay. METHODS: This workshop experience fosters the use of best communication-skills practices and team collaboration in discharge education and planning through reflective observation and role-play. Learners first identify common challenges faced when providing effective care transitions and then identify solutions to encourage patient-centered discharge care practices. Students also have the opportunity to be directly observed providing discharge care and to receive feedback using an observation tool. The materials associated with this publication include guidelines for workshop facilitators, blank video worksheet, completed video worksheet, teaching video, role-play exercise instructions and answer sheet for facilitators, direct observation tool, and workshop evaluation form. RESULTS: The majority of students agreed the workshop would be helpful in practicing effective discharge education (69/75, 92%) and in providing patient-centered care during care transitions (72/75, 96%). Observers and students using the discharge education card reported an average score of 4.3 out of 5 that the observation was a helpful educational experience, and 84% of the completed discharge education tools included comments on areas of improvement or an action plan. DISCUSSION: The tool is brief and user friendly, allowing for this exercise to be completed without difficulty during busy ward days. It also can be completed by residents or attendings depending on time constraints.

Renal cell neoplasms contain shared tumor type-specific copy number variations.

Copy number variant (CNV) analysis was performed on renal cell carcinoma (RCC) specimens (chromophobe, clear cell, oncocytoma, papillary type 1, and papillary type 2) using high-resolution arrays (1.85 million probes). The RCC samples exhibited diverse genomic changes within and across tumor types, ranging from 106 to 2238 CNV segments in a clear-cell specimen and in a papillary type 2 specimen, respectively. Despite this heterogeneity, distinct CNV segments were common within each tumor classification: chromophobe (seven segments), clear cell (three segments), oncocytoma (nine segments), and papillary type 2 (two segments). Shared segments ranged from a 6.1-kb deletion (oncocytomas) to a 208.3-kb deletion (chromophobes). Among common tumor type-specific variations, chromophobes, clear-cell tumors, and oncocytomas were composed exclusively of noncoding DNA. No CNV regions were common to papillary type 1 specimens, although there were 12 amplifications and 12 deletions in five of six samples. Three microRNAs and 12 mRNA genes had a ≥98% coding region contained within CNV regions, including multiple gene families (chromophobe: amylases 1A, 1B, and 1C; oncocytoma: general transcription factors 2H2, 2B, 2C, and 2D). Gene deletions involved in histone modification and chromatin remodeling affected individual subtypes (clear cell: SFMBT and SETD2; papillary type 2: BAZ1A) and the collective RCC group (KDM4C). The genomic amplifications/deletions identified herein represent potential diagnostic and/or prognostic biomarkers.