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AIMS The diagnosis of focal nodular hyperplasia (FNH) and the interpretation of glutamine synthetase (GS) staining can be challenging on biopsies. We aimed to evaluate the reproducibility of needle biopsy diagnosis of FNH, the effect of GS immunohistochemistry on FNH diagnosis, and which histological features are most useful for the diagnosis of FNH. METHODS AND RESULTS The study included virtual needle biopsies generated from 75 resection specimens (30 FNHs, 15 hepatocellular adenomas, 15 hepatocellular carcinomas, and 15 non-lesional liver specimens). Pathologists were reasonably accurate (83.1%) in the diagnosis of FNH with haematoxylin and eosin alone. Ductular reaction and nodularity had the highest sensitivity for a diagnosis of FNH (88.1% and 82.2%, respectively), whereas central scar was the most specific feature (90.6%). The presence of two or more of the classic histological features had 89.6% sensitivity and 86.2% specificity for a diagnosis of FNH. Diagnostic accuracy was significantly higher with the addition of a GS stain. A map-like GS staining pattern was highly specific (99.3%) for FNH. However, GS staining was interpreted as non-map-like in 14.4% of reviews of true FNH cases, and overall interobserver agreement for interpretation of the GS staining pattern was only moderate (kappa = 0.42). CONCLUSIONS Pathologists are reasonably accurate in the diagnosis of FNH on virtual biopsies, and GS staining improves accuracy. However, a subset of FNH cases remain challenging. Steatosis and a pseudo-map-like GS staining pattern were associated with increased difficulty. Therefore, although a map-like GS staining pattern is useful for confirmation of a diagnosis, the lack of a map-like GS staining pattern on needle biopsy does not necessarily exclude a diagnosis of FNH.

Interstitial lung diseases (ILDs) in patients with shortened telomeres have not been well characterized. We describe demographic, radiologic, histopathologic, and molecular features, and p16 expression in patients with telomeres ≤10th percentile (shortened telomeres) and compare them to patients with telomere length >10th percentile. Lung explants, wedge biopsies, and autopsy specimens of patients with telomere testing were reviewed independently by 3 pathologists using defined parameters. High-resolution computed tomography scans were reviewed by 3 radiologists. p16-positive fibroblast foci were quantified. A multidisciplinary diagnosis was recorded. Patients with shortened telomeres (N=26) were morphologically diagnosed as usual interstitial pneumonia (UIP) (N=11, 42.3%), chronic hypersensitivity pneumonitis (N=6, 23.1%), pleuroparenchymal fibroelastosis, fibrotic nonspecific interstitial pneumonia, desquamative interstitial pneumonia (N=1, 3.8%, each), and fibrotic interstitial lung disease (fILD), not otherwise specified (N=6, 23.1%). Patients with telomeres >10th percentile (N=18) showed morphologic features of UIP (N=9, 50%), chronic hypersensitivity pneumonitis (N=3, 16.7%), fibrotic nonspecific interstitial pneumonia (N=2, 11.1%), or fILD, not otherwise specified (N=4, 22.2%). Patients with shortened telomeres had more p16-positive foci (P=0.04). The number of p16-positive foci correlated with outcome (P=0.0067). Thirty-nine percent of patients with shortened telomeres harbored telomere-related gene variants. Among 17 patients with shortened telomeres and high-resolution computed tomography features consistent with or probable UIP, 8 (47.1%) patients showed morphologic features compatible with UIP; multidisciplinary diagnosis most commonly was idiopathic pulmonary fibrosis (N=7, 41.2%) and familial pulmonary fibrosis (N=5, 29%) in these patients. In conclusion, patients with shortened telomeres have a spectrum of fILDs. They often demonstrate atypical and discordant features on pathology and radiology leading to diagnostic challenges.

Key Points Question What is the positive predictive value of myelin oligodendrocyte glycoprotein (MOG)–IgG1 testing in a clinical setting? Findings Of 1260 consecutive patients tested for MOG-IgG1 at the Mayo Clinic over 2 years, 92 (7.3%) were positive, 26 (28%) of whom had their results independently designated as false positive by 2 neurologists. The positive predictive value was 72% and varied with autoantibody titer (≥1:1000, 100%; 1:100, 82%; 1:20-40, 51%) and clinical–magnetic resonance imaging phenotypes at testing (pretest probability: high, 85%; low, 12%). Meaning False-positive MOG-IgG1 results are encountered in clinical practice; caution is advised before assigning a MOG-IgG1–associated disorder diagnosis in patients with low-titer positive results and atypical phenotypes., This diagnostic study seeks to determine the positive predictive value of myelin oligodendrocyte glycoprotein–IgG1 testing in patients in a single tertiary referral center., Importance Myelin oligodendrocyte glycoprotein-IgG1–associated disorder (MOGAD) is a distinct central nervous system–demyelinating disease. Positive results on MOG-IgG1 testing by live cell-based assays can confirm a MOGAD diagnosis, but false-positive results may occur. Objective To determine the positive predictive value (PPV) of MOG-IgG1 testing in a tertiary referral center. Design, Setting, and Participants This diagnostic study was conducted over 2 years, from January 1, 2018, through December 31, 2019. Patients in the Mayo Clinic who were consecutively tested for MOG-IgG1 by live cell-based flow cytometry during their diagnostic workup were included. Patients without research authorization were excluded. Main Outcomes and Measures Medical records of patients who were tested were initially reviewed by 2 investigators blinded to MOG-IgG1 serostatus, and pretest probability was classified as high or low (suggestive of MOGAD or not). Testing of MOG-IgG1 used a live-cell fluorescence-activated cell-sorting assay; an IgG binding index value of 2.5 or more with an end titer of 1:20 or more was considered positive. Cases positive for MOG-IgG1 were independently designated by 2 neurologists as true-positive or false-positive results at last follow-up, based on current international recommendations on diagnosis or identification of alternative diagnoses; consensus was reached for cases in which disagreement existed. Results A total of 1617 patients were tested, and 357 were excluded. Among 1260 included patients tested over 2 years, the median (range) age at testing was 46 (0-98) years, and 792 patients were female (62.9%). A total of 92 of 1260 (7.3%) were positive for MOG-IgG1. Twenty-six results (28%) were designated as false positive by the 2 raters, with an overall agreement on 91 of 92 cases (99%) for true and false positivity. Alternative diagnoses included multiple sclerosis (n = 11), infarction (n = 3), B12 deficiency (n = 2), neoplasia (n = 2), genetically confirmed adrenomyeloneuropathy (n = 1), and other conditions (n = 7). The overall PPV (number of true-positive results/total positive results) was 72% (95% CI, 62%-80%) and titer dependent (PPVs: 1:1000, 100%; 1:100, 82%; 1:20-40, 51%). The median titer was higher with true-positive results (1:100 [range, 1:20-1:10000]) than false-positive results (1:40 [range, 1:20-1:100]; P

Background Patients from various countries may have unique patterns of using complementary and alternative medicine (CAM) and unique reasons for using it. Objective Our objective was to assess the use of CAM among patients from the Gulf region attending the Executive and International Health Program of the Department of General Internal Medicine at Mayo Clinic in Rochester, Minnesota. Methods This cross-sectional survey was administered to all patients who were from the Gulf region and were undergoing outpatient evaluation in the Executive and International Health Program. After their initial medical evaluation by a physician, the patients were invited to anonymously complete the modified International Complementary and Alternative Medicine Questionnaire. Results The survey was completed by 69 patients (41 women, 27 men; mean age, 45.4 years). The most frequently seen providers for CAM treatments were physicians (71.0% of patients), spiritual healers (29.0%), and chiropractors (20.3%). CAM treatments most frequently received from a physician were massage therapy (51.0%), hijama (38.8%), spiritual healing (24.5%), and acupuncture or herbs (16.3%). The most frequently used dietary supplements were ginger (42.0%), bee products (30.4%), and garlic (27.5%). The most common self-help therapies were prayers for health (68.1%), meditation (15.9%), and relaxation techniques (11.6%). CAM therapy, including visits to CAM providers, was used by 92.8% of patients. CAM was mainly used to improve well-being and long-term health conditions rather than for acute illnesses. Conclusion The use of CAM was high among our patients from the Gulf region, and the CAM therapies used by this population differed from the ones used by US patients. Physicians providing care to patients from the Gulf region should be aware of how the use of CAM may affect the care needs of these patients.

AIMIn heart failure (HF), pulmonary venous hypertension (PVH) produces pulmonary hypertension (PH) with remodeling of pulmonary veins (PV) and arteries (PA). In a porcine PVH model, we performed proteomic-based bioinformatics to investigate unique pathophysiologic mechanisms mediating PA and PV remodeling.METHODSLarge PV were banded (PVH, n= 10) or not (Sham, n=9) in piglets. At sacrifice, PV and PA were perfusion labeled for vessel specific histology and proteomics. The PA and PV were separately sampled with laser-capture micro-dissection for mass spectrometry.RESULTSPulmonary vascular resistance (Wood Units; 8.6 versus 2.0) and PA (19.9 versus 10.3) and PV (14.2 versus 7.6) wall thickness/external diameter (%) were increased in PVH (pCONCLUSIONThese findings provide new therapeutic targets to oppose pulmonary vascular remodeling in HF-related PH.TRANSLATIONAL PERSPECTIVEIn heart failure (HF) related (Group 2) PH, despite remodeling of pulmonary veins (PV) and arteries (PA), therapies targeting PA biology altered in Group 1 PH have not shown consistent benefit. In a porcine Group 2 PH model, microdissection allowed vessel specific (PV and PA) proteomics/bioinformatics. In PA and PV, the integrated stress response and mTOR signaling were activated with evidence of dysregulated growth. In PV, many more pathways were altered with broad evidence of disrupted endothelial barrier function and endothelial mesenchymal transition. Findings were confirmed in human specimens and provide new therapeutic targets in Group 2 PH.

To explore the role of the tumor microenvironment (TME) in breast cancer, identify the changes that occur in the TME during breast cancer progression, and explore the possibility of modifying the TME to improve immune checkpoint inhibitor responses. Emerging evidence shows the TME may be shaped by internal and external factors. Preclinical data suggests it may be possible to shift the TME to allow for better immune infiltration. In this review, we summarize emerging evidence of changes in the TME and how it can affect prognosis and responses to therapy. We also examine pre-clinical and clinical research aiming at modulating TME to increase proportion of patients who benefit from immune checkpoint inhibitors. The composition of the TME in breast cancer is likely dynamic and may be altered. These changes may lead to more or less responses to immunotherapy.

Graft-versus-host disease (GVHD) remains a major complication for patients who have undergone hematopoietic stem cell transplantation. The Lerner system is the most widely used histologic grading score for gastrointestinal GVHD but its clinic utility is debated. The aim of our study was to develop a novel histologic grading system for gastrointestinal GVHD that incorporates independent evaluation of both apoptotic counts and crypt destruction. Colonic biopsies taken to assess for GVHD were retrospectively assessed for: Crypt damage (No crypt dropout or ulceration-0; crypt dropout without ulceration-1; ulceration-2) and crypt apoptotic counts (No apoptosis-0; 1-6 apoptotic bodies per 10 contiguous crypts-1;6apoptotic bodies per 10 contiguous crypts-2). The two scores were added together to get an overall grade (0-4). Alternative apoptotic cutoff points were examined. An apoptotic cutoff of9 apoptotic bodies per 10 contiguous crypts marginally improved the area under the curve (AUC), but the AUCs from the resulting novel grade calculations were not significantly different (p = 0.10). Lerner grading was also applied. The study group consisted of an initial analysis cohort (n = 191) and a second validation cohort from a separate institution (n = 97). In the initial analysis cohort, our histologic grading system provided prognostic stratification for GVHD-related death within 6 months (p = 0.0004, AUC = 0.705). The Lerner system performed similarly in terms of providing prognostic stratification for GVHD-related death (p = 0.0001, AUC = 0.707). In the external validation cohort, our histologic grading system was not associated with GVHD-related death (p = 0.14, AUC = 0.621), but the Lerner system was associated with GVHD-related death (p = 0.048, AUC = 0.663). While our grading system may have some advantages compared to the Lerner system, due to lack of reproducibility we do not currently recommend widespread adoption of this system. Nonetheless, we present a standardized tool for assessing both apoptosis and crypt damage. Future studies assessing alternative histologic grading systems with external validation and further examination the lower apoptotic threshold for GVHD diagnosis are warranted.

Knowledge of the histologic constituency of the sinoatrial (SA) node is based on small studies with unevenly distributed ages and subjective assessments of nodal composition, leading to difficulties in interpreting what constitutes true pathology of the SA node. SA nodes from two-hundred normal hearts (10 male and 10 female from each of the first 10 decades of life) were digitally analyzed to assess their histologic composition. Both nodal area and nodal fat content (≥5%) showed a quadratic relationship with age, peaking in the fifth to eighth decades of life. Increased fat content was also more prevalent with increased BMI (≥25 kg/m2). No differences between sexes were observed. Mean nodal collagen ranged from 7.1% to 50.3%, without a statistically significant differences by age or body mass index (BMI). The data suggests that the designation of pathologic fibrosis should be reserved for SA nodes with >50% collagen content. These findings expand and refine our understanding of the anatomy of the SA node.

Background Cutaneous squamous cell carcinomas (CSCC) involving the head and neck are common, but initial presentation or recurrence limited to the cranial nerves is rare. Methods We conducted a retrospective study of 21 patients with clinical perineural invasion (PNI) from CSCC and no measurable disease by RECIST 1.1. Patients treated with radiotherapy or chemoradiotherapy were included. Results The median time from symptom onset until diagnosis was 13.0 months (2.6-83.1). All patients received radiotherapy. Fourteen received concurrent systemic therapy. The median follow-up time was 30.5 months (1.1-106.0). Ten patients recurred, with the majority being locoregional. The 2-year overall survival rate was 85%. The median progression-free survival (PFS) was 21.5 months with an estimated 2-year PFS of 44.5% (95%CI: 22.3-66.8). Conclusions CSCCs with clinical PNI alone are difficult to diagnose and can have a long interval between appearance of symptoms and diagnosis. They can successfully be treated with chemoradiotherapy. However, many patients still suffer from locoregional recurrences.

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a cohort of 67 patients with histologically defined PXA (n=53, 79%) or anaplastic PXA (A-PXA, n=14, 21%), including copy number analysis (ThermoFisher Oncoscan, n=67), methylation profiling (Illumina EPIC array, n=43) and targeted next generation sequencing (n=32). The most frequent alterations were CDKN2A/B deletion (n=63; 94%) and BRAF p.V600E (n=51, 76.1%). In 7 BRAF p.V600 wild-type cases, alternative driver alterations were identified involving BRAF, RAF1 and NF1. Downstream phosphorylation of ERK kinase was uniformly present. Additional pathogenic alterations were rare, with TERT, ATRX and TP53 mutations identified in a small number of tumors, predominantly A-PXA. Methylation-based classification of 46 cases utilizing a comprehensive reference tumor allowed assignment to the PXA methylation class in 40 cases. A minority grouped with the methylation classes of ganglioglioma or pilocytic astrocytoma (n=2), anaplastic pilocytic astrocytoma (n=2) or control tissues (n=2). In 9 cases, tissue was available from matched primary and recurrent tumors, including 8 with anaplastic transformation. At recurrence, two tumors acquired TERT promoter mutations and the majority demonstrated additional non-recurrent copy number alterations. Methylation class was preserved at recurrence. For 62 patients (92.5%), clinical follow-up data were available (median follow-up, 5.4years). Overall survival was significantly different between PXA and A-PXA (5-year OS 80.8% vs. 47.6%; P=0.0009) but not progression-free survival (5-year PFS 59.9% vs. 39.8%; P=0.05). WHO grade remained a strong predictor of overall survival when limited to 38 cases defined as PXA by methylation-based classification. Our data confirm the importance of WHO grading in histologically and epigenetically defined PXA. Methylation-based classification may be helpful in cases with ambiguous morphology, but is largely confirmatory in PXA with well-defined morphology.

The diagnosis of inflammatory bowel disease (IBD)-associated dysplasia is challenging, and past studies have demonstrated considerable interobserver variability in such diagnoses. This study aimed to assess interobserver agreement in IBD dysplasia diagnoses among subspecialty GI pathologists and to explore the impact of mentorship on diagnostic variability. Twelve GI pathologist mentees and 7 GI pathologist mentors reviewed 163 digitized slides. Participants rendered a diagnosis of negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, or high-grade dysplasia and provided a confidence level for each case. Interobserver agreement and reliability were assessed using Cohen's and Fleiss' kappa (κ) statistics and intraclass correlation coefficient (ICC) analysis. The overall κ coefficient was 0.42 (95% CI: 0.38-0.46). The overall ICC was 0.67 (95% CI: 0.62-0.72). Κ coefficients ranged from 0.31 to 0.49 for mentor/mentee pairs and from 0.34 to 0.55 for pairs of mentees of the same mentor. The combined κ coefficient was 0.44 (95% CI: 0.39-0.48) for all mentees and 0.39 (95% CI: 0.34-0.43) for all mentors. Common features in low agreement cases included mucosal atrophy, areas of stark contrast, serrations, decreased goblet cells, absent surface epithelium, and poor orientation. Participants were confident in most diagnoses, and increased confidence levels generally correlated with higher interobserver agreement. Interobserver agreement among subspecialist GI pathologists in this curated cohort of IBD dysplasia cases was fair to moderate. Mentorship during GI pathology fellowship does not appear to be a significant factor contributing to interobserver variability, but increased experience also does not seem to improve interobserver agreement.

Background Median overall survival is 12 to 15 months in patients with metastatic adrenal cortical carcinoma (ACC). Etoposide, doxorubicin, and cisplatin with or without the adrenolytic agent mitotane is considered the best first-line approach in this context, but has limited activity and no curative potential; additional salvage therapeutic options are needed. Methods Fifteen total patients with recurrent/metastatic ACC were treated with single-agent multikinase inhibitors (MKI) (n = 8), single-agent PD-1 inhibition (n = 8), or cytotoxic chemotherapy plus PD-1 inhibition (n = 4) at our institution as later-line systemic therapies in efforts to palliate disease and attempt to achieve a therapeutic response when not otherwise possible using standard approaches. Results Two of 8 patients (25%) treated with single-agent MKI achieved a partial response (PR), including 1 PR lasting 23.5 months. Another 3 patients (38%) had stable disease (SD); median progression-free survival (PFS) with single-agent MKI was 6.4 months (95% confidence interval [CI] 0.8—not reached). On the other hand, 2 of 12 patients (17%) treated with PD-1 inhibitors (either alone or in combination with cytotoxic chemotherapy) attained SD or better, with 1 patient (8%) achieving a PR; median PFS was 1.4 months (95% CI 0.6-2.7). Conclusions Our single-institution experience suggests that select ACC patients respond to late-line MKI or checkpoint inhibition despite resistance to cytotoxic agents. These treatments may be attractive to ACC patients with limited other therapeutic options. The use of MKI and immunotherapy in ACC warrants prospective investigation emphasizing parallel correlative studies to identify biomarkers that predict for response.

Spiritual health is important in managing and coping with chronic and debilitating illnesses, such as neurodegenerative diseases. However, few spiritual interventions have addressed this population. This article quantitatively and qualitatively evaluates outcomes of a spiritual life review in neurodegenerative diseases patients. The majority of participants improved or maintained quality of life and spiritual/emotional well-being following the intervention. Spiritual life review may be an important intervention in the comprehensive care of patients with neurodegenerative diseases.

Objectives: To describe the feasibility of a chaplain-led spiritually focused life review interview and the development of a spiritual legacy document (SLD) for patients with advanced diseases and to describe changes in spiritual well-being (SWB), spiritual coping strategies (SC), and quality of life (QOL) after receiving the SLD. Patients and Methods: In all, 130 patients and support person (SP) pairs were recruited from July 2012 to January 2019. Following enrollment, demographic information was gathered and baseline questionnaires were administered. Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being Scale (FACIT-Sp-12) and a linear analog scale assessment (LASA) measured SWB. LASAs also measured QOL and emotional well-being (EWB). Positive Religious Coping Scale (RCOPE) measured SC. After completion of baseline forms, participants were interviewed (individually) by a chaplain. Interviews were digitally recorded, transcribed, and verified. Transcripts were edited and participants were given the opportunity to make adaptations. The participant-approved draft was then developed into a professionally printed SLD. Follow-up questionnaires were administered to assess change. Results: Significant improvements from baseline to post-SLD follow-up were found for patients on the LASAs: SWB (average 7.7-8.3, P = .01), QOL (average 6.7-7.3, P = .03), EWB (average 6.9-7.5, P = .01), and on the positive RCOPE (average 1.8-2.0, P = .007). Effect sizes were approximately 0.25. Considering any improvement, 61.0% improved their positive RCOPE score, 46.6% improved EWB, and 39.7% improved SWB. No significant changes were found on the FACIT-Sp-12. No significant changes were found for SPs. Conclusion: The results suggest that the primary participants who completed the study benefited by significantly increasing their QOL, SWB, EWB, and SC.

BACKGROUND: Regular physical activity after breast cancer diagnosis improves survival rates and quality of life (QOL). However, breast cancer survivors rarely meet guidelines for recommended levels of physical activity. Wellness coaching interventions (WCIs) have improved exercise and health behaviors in other populations but have rarely been studied in breast cancer. OBJECTIVES: This study assessed the feasibility and effectiveness of WCIs for increasing physical activity in breast cancer survivors; secondary measures included changes in dietary habits, weight, and QOL. METHODS: Twenty obese or overweight breast cancer survivors who recently completed active breast cancer treatment were recruited into a single-arm 12-week WCI pilot feasibility study. The intervention comprised 1 in-person wellness coaching visit followed by 4 telephone calls over 12 weeks and 12 weekly emails containing wellness recommendations. Physical activity level, dietary habits, weight, and QOL were all self-reported. FINDINGS: The 20 breast cancer survivors demonstrated 100% adherence to the initial wellness coaching visit and 96% adherence to the 4 telephone calls. Significant improvements from before to after intervention were seen in physical activity level and dietary habits and in some aspects of QOL. Forty percent of participants achieved the 3% postintervention weight-loss goal, but this was not sustained at 30 weeks.

Recently, a novel isoform of anaplastic lymphoma kinase, with alternative transcription initiation (ALKClinicopathological characteristics were abstracted for 324 patients with metastatic melanoma (MM). IHC, fluorescence in-situ hybridisation and RNA-based digital molecular analysis assays were performed on archival tissue from 173 stage III and 192 stage IV tumours. ALKPresence of ALK

Mediastinal lesions are uncommon; studies on their distribution are, in general, small and from a single institution. Furthermore, these studies are usually based on pathology or surgical databases and, therefore, miss many lesions that did not undergo biopsy or resection. Our aim was to identify the distribution of lesions in the mediastinum in a large international, multi-institutional cohort.At each participating institution, a standardized retrospective radiology database search was performed for interpretations of computed tomography, positron emission tomography-computed tomography, and magnetic resonance imaging scans including any of the following terms: "mediastinal nodule," "mediastinal lesion," "mediastinal mass," or "mediastinal abnormality" (2011-2014). Standardized data were collected. Statistical analysis was performed.Among 3308 cases, thymomas (27.8%), benign mediastinal cysts (20.0%), and lymphomas (16.1%) were most common. The distribution of lesions varied among mediastinal compartments; thymomas (38.3%), benign cysts (16.8%), and neurogenic tumors (53.9%) were the most common lesions in the prevascular, visceral, and paravertebral mediastinum, respectively (p0.001). Mediastinal compartment was associated with age; patients with paravertebral lesions were the youngest (p0.0001). Mediastinal lesions differed by continent or country, with benign cysts being the most common mediastinal lesions in the People's Republic of China, thymomas in Europe, and lymphomas in North America and Israel (p0.001). Benign cysts, thymic carcinomas, and metastases were more often seen in larger hospitals, whereas lymphomas and thymic hyperplasia occurred more often in smaller hospitals (p 0.01).Our study confirmed that the spectrum and frequency of mediastinal lesions depend on mediastinal compartment and age. This information provides helpful demographic data and is important when considering the differential diagnosis of a mediastinal lesion.

Meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is a rare tumor with propensity for recurrence and metastasis. Although multiple classification schemes have been proposed, optimal risk stratification remains unclear, and the prognostic impact of fusion status is uncertain. We compared the 2016 WHO CNS tumor grading scheme (CNS-G), a three-tier system based on histopathologic phenotype and mitotic count, to the 2013 WHO soft-tissue counterpart (ST-G), a two-tier system based on mitotic count alone, in a cohort of 133 patients [59 female, 74 male; mean age 54 years (range 20–87)] with meningeal SFT/HPC. Tumors were pathologically confirmed through review of the first tumor resection (n = 97), local recurrence (n = 35), or distant metastasis (n = 1). A STAT6 immunostain showed nuclear expression in 132 cases. NAB2–STAT6 fusion was detected in 99 of 111 successfully tested tumors (89%) including the single STAT6 immunonegative tumor. Tumors were classified by CNS-G as grade 1 (n = 43), 2 (n = 41), or 3 (n = 49), and by ST-G as SFT (n = 84) or malignant SFT (n = 49). Necrosis was present in 16 cases (12%). On follow-up, 42 patients had at least one subsequent recurrence or metastasis (7 metastasis only, 33 recurrence only, 2 patients had both). Twenty-nine patients died. On univariate analysis, necrosis (p = 0.002), CNS-G (p = 0.01), and ST-G (p = 0.004) were associated with recurrence-free (RFS) but not overall survival (OS). NAB2–STAT6 fusion type was not significantly associated with RFS or OS, but was associated with phenotype. A modified ST-G incorporating necrosis showed higher correlation with RFS (p = 0.0006) and remained significant (p = 0.02) when considering only the primary tumors. From our data, mitotic rate and necrosis appear to stratify this family of tumors most accurately and could be incorporated in a future grading scheme. Electronic supplementary material The online version of this article (10.1007/s00401-018-1952-6) contains supplementary material, which is available to authorized users.

PurposeWe assessed the decision-making of individuals pursuing genomic sequencing without a requirement for pretest genetic counselling. We sought to describe the extent to which individuals who decline genetic counselling reported decisional conflict or struggled to make a decision to pursue genomic testing.MethodsWe administered a 100-item survey to 3037 individuals who consented to the Return of Actionable Variants Empirical study, a genomic medicine implementation study supported by the National Institutes of Health (USA) eMERGE consortium. The primary outcomes of interest were self-reported decisional conflict about the decision to participate in the study and time required to reach a decision.ResultsWe received 2895 completed surveys (response rate=95.3%), and of these respondents 97.8% completed the decisional conflict scale in its entirety. A majority of individuals (63%) had minimal or no decisional conflict about the pursuit of genomic sequencing and were able to reach a decision quickly (78%). Multivariable logistic regression analyses identified several characteristics associated with decisional conflict, including lower education, lower health literacy, lower self-efficacy in coping, lack of prior experience with genetic testing, not discussing study participation with a family member or friend, and being male.ConclusionAs genomic sequencing is used more widely, genetic counselling resources may not be sufficient to meet demand. Our results challenge the notion that all individuals need genetic counselling in order to make an informed decision about genomic sequencing.

OBJECTIVE Many adults struggle with eating healthfully. To address this problem, dietitians and a physician at a worksite wellness center designed and implemented a healthy eating program to identify and reduce barriers and to improve nutrition knowledge, confidence, and eating habits. METHODS A single cohort study design of members of a worksite wellness center who attended the program. RESULTS Eight-six participants demonstrated significant improvement in reducing perceived barriers (P

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignant tumor and has a poor prognosis. The prognostic factors associated with outcome remain poorly defined. In this study, we investigated the role of an important cell apoptosis initiator, Bcl-2 interacting mediator of cell death (Bim), by evaluating its expression and association with other clinicopathological features in ICCs. We analyzed 56 cases of ICC with clinical follow-up. The expression of Bim in ICC cells and other cellular components was evaluated by immunohistochemistry. Bim expression was considered up-regulated if Bim was detected in 10% or more of tumor cells. Of the 56 ICC samples, 19 (34%) had high Bim expression level, 15 (27%) were completely negative, and 22 (39%) were classified as low Bim expression (

Background: We hypothesized that pulmonary venous hypertension in heart failure (HF) leads to predominate remodeling of pulmonary veins and that the severity of venous remodeling is associated with the severity of pulmonary hypertension (PH) in HF. Methods: Patients with HF (n=108; 53 preserved and 55 reduced ejection fraction) with PH (HF-PH; pulmonary artery systolic pressure [PASP] ≥40 mm Hg) were compared to normal controls (n=12) and patients with primary pulmonary veno-occlusive disease (PVOD; n=17). In lung specimens from autopsy (control, HF-PH, and 7 PVOD) or surgery (10 PVOD), quantitative histomorphometry was performed in all analyzable arteries (n=4949), veins (n=7630), and small indeterminate vessels (IV; n=2168) to define percent medial thickness (arteries) and percent intimal thickness (%IT) (arteries, veins, and IV) relative to external diameter. Results: The average arterial percent medial thickness (control, 6.9; HF-PH, 11.0; PVOD, 15.0), arterial %IT (control, 4.9; HF-PH, 14.9; PVOD, 31.1), venous %IT (control, 14.0; HF-PH, 24.9; PVOD, 43.9), and IV %IT (control, 10.6; HF-PH, 25.8; PVOD, 50.0) in HF-PH were higher than controls ( P P ≤0.005 for all). PASP (mm Hg) was lower in HF-PH (median, 59 [interquartile range, 50–70]) than in PVOD (median, 91 [interquartile range, 82–103]). PASP correlated with arterial percent medial thickness ( r =0.41) and arterial %IT ( r =0.35) but more strongly with venous %IT ( r =0.49) and IV %IT ( r =0.55) ( P Conclusions: In HF, PH is associated with global pulmonary vascular remodeling, but the severity of PH correlates most strongly with venous and small IV intimal thickening, similar to the pattern observed in PVOD. These findings expand our understanding of the pathobiology of PH in HF.

To determine whether CSF leucine‐rich glioma‐inactivated 1(LGI1)‐IgG titer, index or IgG subclass has prognostic significance, we tested serum and CSF specimens collected concomitantly from 39 seropositive patients. LGI1‐IgG index was elevated (>1) in 21 patients (54%), suggesting intrathecal synthesis. Patients with worse outcome at last follow‐up (modified Rankin Scale >2) had significantly higher index (median 6.57 vs. 0.5, P = 0.048) compared to those with better outcome. Higher CSF LGI1‐IgG4 subclass‐specific titer and index correlated with worse outcome (P

Aiming to assess the association between measures of obesity and outcomes in coronary artery disease (CAD) patients. We included consecutive patients referred to cardiac rehabilitation because of prior CAD events, who were classified using BMI groups and sex-specific tertiles of waist-to-hip ratio (WHR). Follow-up was ascertained using a population-based, record linkage system that consists of complete data on all residents. A major cardiovascular event (MACE) was defined as the composite outcome including acute coronary syndromes, coronary revascularization, ventricular arrhythmias, stroke or death from any cause. The association between obesity measures and MACE was assessed using cox proportional hazards models adjusted for potential confounders. The cohort included 1529 patients (74% men) mean age ± SD 63.1±12.5 years, 40% were obese by BMI. Eighty-eight percent of men and 57% of women were classified as having central obesity by WHR. Median follow-up was 5.7 years and 415 patients had a MACE event. After adjustment, a high WHR tertile was a significant predictor for MACE in women (HR=1.85 [95% Cl: 1.16, 2.94]; p=0.01), but not in men (HR=0.92 [95%CI: 0.69, 1.22]; p=0.54). This relationship in women persisted after further adjustment for BMI (HR=1.75 [95%CI: 1.07, 2.87]; p=0.03). Obesity by BMI was not associated with MACE in either men (HR=1.07 [95%CI: 0.76, 1.51]; p=0.69) or women (HR=0.98 [95%CI: 0.62, 1.56]; p=0.95). In conclusion WHR is associated with a higher risk of MACE among women with CAD but not in men. There was no obesity paradox when assessing obesity by BMI and MACE in CAD patients when including non-fatal events.

Yoga is increasing in popularity in the United States and across the globe. However, most yoga programs are provided outside the worksite; although many companies offer worksite wellness programs, at present there is limited documentation regarding the potential benefits of participating in a worksite yoga program. Therefore, the purpose of this project was to examine the potential effect of a worksite yoga program on self-acceptance, quality of life, and perceived stress. A prospective cohort pilot study that examined a structured worksite yoga program was designed and tailored to individuals new to yoga. The 8-week Yoga Foundations program was conducted at an academic medical center's worksite wellness center with 86 subjects. Outcome measures were the 36-item Self-Acceptance Scale; a six-item quality-of-life measure that assesses overall, social, mental, physical, emotional, and spiritual well-being; and the ten-item Perceived Stress Scale. Participants demonstrated significant improvement in their overall self-acceptance (p < 0.001), quality of life (p < 0.001), and perceived stress (p < 0.001) levels. They also highly rated the yoga instructors and the weekly format of the program. Participation in a Yoga Foundations program was associated with improvements in self-acceptance, quality of life and stress levels in worksite wellness center members. Future studies should use randomized designs and examine other wellness domains to learn more about the potential benefits of worksite yoga programs.

Spirituality is an important component of spiritual well-being (SWB) and quality of life in the elderly. The Hear My Voice study explores the impact of spiritual life review and spiritual legacy do...

Nonmalignant hematologic conditions are extremely prevalent and contribute significantly to the global burden of disease. The US health care system may soon face a shortage of specialists in nonmalignant hematology. We sought to identify factors that lead hematology-oncology fellows to pursue (or not to pursue) careers in nonmalignant hematology. Cross-sectional, web-based survey distributed to 149 graduates of a hematology-oncology fellowship program at a large academic medical center between 1998 and 2016. Eighty-six out of 149 graduates responded (57.7%); most (59 [68.6%]) practice at an academic medical center. Respondents spend a mean of 61% of their time in clinical practice, 23.7% conducting research, 5.2% in education, and 5.2% in administration. Those in clinical practice spend a mean of 52.1% of their time in solid tumor oncology, 37.5% in hematologic malignancies, and 10% in nonmalignant hematology; only 1 spent >50% of time practicing nonmalignant hematology. Factors most significantly affecting choice of patient population included clinical experience during fellowship and intellectual stimulation of the patient population/disease type. Factors that could have most significantly influenced a decision to spend more time in nonmalignant hematology included increased exposure/access to role models and mentors and opportunities for better career growth/advancement. Fellowship graduates spend >50% of their time in clinical practice, but almost none spend a significant amount of time practicing nonmalignant hematology. Given the growing number of patients with nonmalignant hematologic conditions and a possible future provider shortage, medical trainees should be encouraged to pursue careers in nonmalignant hematology.

Objectives Most giant cell tumors of bone (GCTs) occur in patients aged 20 to 40 years. We analyzed features of GCT in patients 55 years or older. Methods GCTs were examined for fibrosis, matrix, cystic change, histiocytes, mitoses, and necrosis. Clinical/radiologic data were collected. Results Thirty-four (5%) of 710 GCTs occurred in patients older than 55 years (14/20 male/female; 56-83 years) in long bones (n = 24), vertebrae (n = 6), pelvis (n = 3), and metacarpal (n = 1). Imaging was classic in 26 of 27 cases; one case appeared malignant. Morphologic patterns included fibrosis (n = 29), bone formation (n = 19), cystic change (n = 8), necrosis (n = 8), foamy histiocytes (n = 7), and secondary aneurysmal bone cyst formation (n = 1). Mitoses ranged from 0 to 18 per 10 high-power fields. Six recurred; one patient developed metastasis. Four of five cases harbored H3F3A mutations. Conclusions GCTs in patients 55 years or older share pathologic characteristics with those arising in younger adults. Fibrosis and reactive bone are common, potentially leading to diagnostic confusion in this population. No histologic features correlate with adverse outcome.

Objectives The high prevalence of stress at the workplace has been well documented; however, few studies have investigated the efficacy of worksite resiliency programs. Therefore, the objec- tive of this project was to examine the impact of a worksite resilience training program on improving resiliency and health behaviors in healthcare employees. Methods Between 2012 and 2016, 137 adult wellness center members of a healthcare institution participating in a single-arm cohort study of a 12-week resiliency training program were assessed at baseline, end of intervention, and at 3-month follow-up. Results Statistically significant (p ≤ .01) improvements were seen at the end of the intervention and extending to 3 months follow-up for resiliency, perceived stress, anxiety level, quality of life, and health behaviors. Conclusions These results support the premise that worksite programs designed to improve resiliency in healthcare employees have efficacy in improving resiliency, quality of life and health behaviors. Given the importance of stress and burnout in healthcare employees, future randomized studies are warranted to determine more clearly the impacts of this type of resiliency intervention for improving the wellness of healthcare workers.

Accurate risk stratification of smooth muscle tumors (SMTs) is essential for appropriate patient management. Yet, the rarity of SMTs of the vagina and vulva makes development of a prognostically meaningful classification system challenging. While 2 classification methods for vulvar SMTs and 1 for vaginal SMTs have been proposed, it is our experience that many pathologists tend to apply criteria for uterine SMTs when evaluating vulvovaginal tumors. We retrospectively reviewed a large cohort of vulvovaginal SMTs with clinical follow-up and evaluated which method most accurately classified tumors according to patient outcome. A total of 71 tumors, 53 vaginal (75%) and 18 vulvar (25%), from 71 patients were identified. All tumors were centrally examined for degree of cytologic atypia, morphology (spindled, epithelioid, myxoid), mitotic index per 10 high power fields, atypical mitotic figures, tumor cell necrosis, ischemic necrosis, tumor interface (circumscribed or infiltrative) and margin status. Clinical features were recorded for each patient. Follow-up was available for 63 patients (89%), and ranged from 1 to 234 months (median: 64 mo). While site-specific and uterine criteria showed equally excellent sensitivity in classifying smooth muscle neoplasms as leiomyosarcoma according to patient outcome, uterine criteria showed improved specificity relatively to site-specific methods in classifying tumors as nonsarcoma according to patient outcome. We recommend that uterine SMT criteria and nomenclature be adopted for evaluation and classification of vulvovaginal SMTs.

The guideline-recommended lipid panel for cardiovascular disease (CVD) risk assessment measures total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol. Measured cholesterol in subfractions of HDL and LDL purportedly improve CVD risk prediction. Homogenous enzymatic methods are now available for measurement of the cholesterol within small dense LDL (sLDL), small dense HDL (HDL3), and triglyceride-rich lipoproteins (TRL). For meaningful interpretation of these measurements, an understanding of the potential sources and extent of result variability is needed. The smallest difference between serial measurements within a patient that likely reflects a change in clinical status is called the reference change value (RCV). Biological variability and reference change values (RCV) are well-characterized for basic lipids but there is limited information for sLDL, HDL3 or TRL. The objective of this study was to determine intra- and inter-individual variability for sLDL, HDL3, and TRL in a healthy reference population. Serum samples were collected from 24 healthy subjects (n=14 female/10 male) daily for three days (non-fasting), daily for five days (fasting), weekly for four weeks (fasting), and monthly for 7 months (fasting). sLDL, HDL3, and TRL cholesterol were measured in duplicate by enzymatic colorimetric assays (Denka, Japan) on a Roche Cobas c501. Each source of variability (between subject, within subject, and analytical) was calculated using random-effects regression models to estimate each variance component including the overall variation, standard deviation (SD), coefficient of variation (CV), and proportion of total variance (between-subject, within-subject, and analytical). Using these analytical and biological variances, the reference change value (RCV), index of individuality (IoI), and intraclass correlation coefficient (ICC) were determined. Analytic variability (CVa) from monthly testing was 1.2%, 1.1%, and 1.5% for sLDL, HDL3, and TRL, respectively. Monthly within-subject variability (CVw) was 17.1% for sLDL, 7.4% for HDL3 and 25.7% for TRL. Monthly between-subject variability (CVb) was 32.2%, 13.93%, and 33.4% for sLDL, HDL3, and TRL, respectively. Most of the monthly variation was attributed to between-subject variation for all three tests. Within-subject variation accounted for 37% of TRL variation and 22% for both sLDL and HLD3. Within-subject RCVs for monthly measurements were 16.9mg/dL for sLDL, 5.3mg/dL for HDL3, and 15.1mg/dL for TRL. IoIs for monthly testing were 0.81 for TRL, 0.57 for sLDL, and 0.61 for HDL3. Our data demonstrate that sLDL, HDL3, and TRL show low analytical variability, moderate within-subject variability, but high between-subject variability when measured by homogenous assays in a healthy population. The IoI value (>0.6) for TRL suggests use of a reference interval is appropriate for result interpretation. Conversely, clinical cut-points may be more useful than reference intervals for sLDL and HDL3 which had IoIs ~0.6. These findings may be useful for clinical interpretation, particularly when comparing successive measurements of these analytes.

Introduction: Through real-time monitoring of biophysical parameters, physical activity monitors may represent a medium by which urologists can actively engage patients and improve treatment outcomes. We examined patient reported acceptance of physical activity monitor technology in an ambulatory urology setting.Methods: Patients treated at a single urology department during a 6-month period were identified. A web based survey was conducted evaluating patient characteristics and acceptance of physical activity monitors.Results: A total of 1,043 (19%) patients completed the survey, of whom 210 (20%) reported using physical activity monitors for health and wellness. Overall 854 (82%) respondents were willing to use these devices for urological care. Compared to patients who disagreed, those willing to use physical activity monitors for medical care reported greater perceived medical benefit (86% vs 14%), improved communication (85% vs 26%), confidentiality (89% vs 45%), less interference with daily ...

Glomus tumors are rare mesenchymal neoplasms with a phenotype akin to the modified smooth muscle cells of the glomus body. Most are benign, but rare examples show malignant histologic characteristics and aggressive behavior. We recently encountered a malignant glomus tumor with BRAF V600E mutation. We sought to study a large cohort for this mutation, with particular attention to associated malignant histologic characteristics. Tumors were classified based on WHO criteria as benign, uncertain malignant potential (glomus tumors of uncertain malignant potential-GT-UMP), or malignant. Tumors were screened for BRAF V600E by immunohistochemistry, and positive staining was evaluated further by Sanger sequencing. A total of 102 glomus tumors were included and classified as benign (57, 56%), GT-UMP (15, 15%) and malignant (30, 29%). Tumors occurred in patients aged 8 to 89.9 years (median: 50.2), without sex predilection (55% men). Most occurred in the superficial soft tissue (84%) and upper extremities (55%). Six of 95 tested cases had BRAF V600E mutation (6%), including 0 of 57 benign tumors, 3 of 14 GT-UMP (21%), and 3 of 24 malignant tumors (12%). Follow-up was obtained for 59 cases (median: 75.7 mo, range: 7.8 to 268.5). Three of 11 malignant tumors (27%) had progressive disease: 1 with metastasis to brain and heart, 1 with enlarging residual disease, and 1 with recurrence. Two of 4 GT-UMP (50%) had progressive disease: 1 with metastasis to lung, and 1 with local recurrence (50%). Three of 44 benign tumors (7%) had local recurrence. Two of 5 patients with BRAF V600E had progression, including 1 GT-UMP with local recurrence and 1 malignant tumor with enlarging residual disease. In summary, BRAF V600E mutation was detected in 6% of glomus tumors, all of which were malignant or GT-UMP. This mutation may be associated with a malignant phenotype, although study of additional cases is needed. In patients with progressive disease, BRAF could be a promising therapeutic target.

A distinct subset of thoracic sarcomas with undifferentiated rhabdoid morphology and SMARCA4 inactivation has recently been described, and potential targeted therapy for SMARC-deficient tumors is emerging. We sought to validate the clinicopathological features of SMARCA4-deficient thoracic sarcomas. Clinicopathological information was gathered for 40 undifferentiated thoracic tumors with rhabdoid morphology (mediastinum (n=18), lung (n=14), pleura (n=8)). Thymic carcinomas (n=11) were used as a comparison group. Immunohistochemistry included BRG1 (SMARCA4), BRM (SMARCA2), INI-1 (SMARCB1), pan-cytokeratin, desmin, NUT, S-100 protein, TTF1, CD34, and SOX2. BRG1 loss was present in 12 of 40 rhabdoid thoracic tumors (30%): 7 of 18 in mediastinum (39%), 2 of 8 in pleura (25%), and 3 of 14 in lung (21%). All BRG1-deficient tumors tested for BRM (n=8) showed concomitant loss. All thymic carcinomas showed retained BRG1 and INI-1. Morphologically, tumors with BRG1 loss showed sheets of monotonous ovoid cells with indistinct cell borders, abundant eosinophilic cytoplasm, and prominent nucleoli. Scattered areas with rhabdoid morphology (ie, eccentric nuclei, dense eosinophilic cytoplasm, discohesion) were present in all the cases. SMARCA4/BRG1-deficient sarcomas showed rare cells positive for cytokeratin in 10 cases (83%). One showed rare TTF1-positive cells. All were negative for desmin, NUT, and S-100 protein. CD34 was positive in three of five (60%) BRG1-deficient tumors tested. SOX2 was positive in all four BRG1-deficient tumors tested, and negative in all seven tested cases with retained BRG1. SMARCA4/BRG1-deficient sarcomas occurred at median age of 59 years (range 44-76) with male predominance (9:3) and had worse 2-year survival compared with BRG1-retained tumors (12.5% vs 64.4%, P=0.02). SMARCA4-deficient thoracic sarcomas can be identified based on their distinctive high-grade rhabdoid morphology, and the diagnosis can be confirmed by immunohistochemistry. Identification of these tumors is clinically relevant due to their aggressive behavior, poor prognosis, and potential targeted therapy.

Reflection exposes performance gaps and is a step in the process of behavior change among adult learners. However, little is known about the relationships between reflection and behavior change in CME. Our objectives were to measure associations between validated reflection scores and behavior change among CME participants and to identify associations between reflection and characteristics of CME presentations.This was a cohort study of attendees at a national hospital medicine CME course. Participants provided reflection scores for each presentation and planned commitment-to-change (CTC) statements at the conclusion of the course. Reflection scores from 1 (strongly disagree) to 5 (strongly agree) were averaged for each presentation. CTC statements were linked to their accompanying presentations. A 3-month postcourse survey was conducted to assess if planned CTCs were successfully implemented.In all, 223 of 281 participants (79.4%) returned evaluations. Of the 195 planned CTC statements available for postcourse analysis, 128 (65.6%) were implemented. Reflection scores correlated with the number of planned CTC statements across all presentations (Pearson correlation, 0.65; P.001). In addition, higher reflection scores (mean [SD]) were associated with the presence of audience response opportunities (Yes: 4.13 [0.18] versus No: 3.96 [0.16]; P = .01) and the use of clinical cases (Yes: 4.09 [0.18] versus No: 3.86 [0.12]; P.01).To our knowledge, this is the first study to show a relationship between participant reflection and CTC in conference-based CME. Presentations that incorporate clinical cases and audience response systems seem to stimulate participant reflection and behavior change.

Introduction Thymic carcinomas are aggressive tumors. Biomarkers and alternative treatment modalities are needed. We studied the expression of p16 and cytogenetic abnormalities of cyclin-dependent kinase inhibitor 2A gene ( CDKN2A ) and correlated findings with clinical features and outcome in a large cohort of thymic carcinomas. Methods Thymic carcinomas (1963–2013) were stained with p16. Fluorescence in situ hybridization was utilized to assess for the presence of CDKN2A gene (at 9p21). Statistical analysis was performed. Results A total of 27 patients (including 15 men) with thymic carcinoma at a median age of 51.7 years at time of surgery and available follow-up information were included. Loss of p16 expression was found in 12 of 26 cases (46.2%) and was associated with worse recurrence and metastasis–free survival ( p = 0.01), which in multivariate analysis was independent of resection status ( p = 0.007) and T stage ( p = 0.01). Four of 22 tumors (18.2%) showed homozygous CDKN2A deletion that was correlated with loss of p16 expression (p=0.02). In tumors of the squamous cell carcinoma subtype, loss of p16 expression was associated with worse recurrence and metastasis–free survival ( p = 0.006) and overall survival ( p = 0.0009). Patients with thymic squamous cell carcinomas lacking p16 expression were younger ( p = 0.006). Although similar trends for younger age were noted in patients with thymic squamous cell carcinomas with homozygous CDKN2A deletion, the small number of such cases (n = 2) did not allow for statistical analysis. Conclusions Loss of p16 expression and homozygous deletion of CDKN2A are promising prognostic biomarkers in thymic carcinoma. On the basis of our findings, a subset of thymic carcinomas have the potential to respond to CDK4/6 inhibitors; however, further functional studies are needed.

Striking cardiovascular health disparities exist among African-Americans in Minnesota compared to Whites; however, community-based interventions to address cardiovascular disease risk are lacking. This study explored participant perceptions of a culturally tailored, cardiovascular disease prevention program developed using a community-based participatory research process. Research participation perceptions, program benefits, and program satisfaction/acceptability were analyzed using a mixed-methods approach. Overall, acceptability was high. Findings highlight the favorable inclusion of African-Americans (research perception), knowledge gained about healthy lifestyle practices (benefits), and quality of the curriculum/speakers (satisfaction). Community-based participatory research may be useful in fostering the acceptability of behavior change interventions among marginalized African-American communities.

Despite the current classification of high-grade serous carcinoma (HGSCA) and low-grade serous carcinoma (LGSCA) as mutually exclusive diseases based on morphology and molecular pathogenesis, cases with mixed morphologic features of HGSCA and LGSCA have been reported. Herein we assess the clinicopathologic, immunohistochemical (IHC), and molecular genetic characteristics of a group of these cases, which we termed indeterminate grade serous carcinoma (IGSCA) in comparison with groups of HGSCA and LGSCA. Using the World Health Organization (WHO) classification criteria, we selected 27 LGSCA and 19 IGSCA for detailed morphologic study. Thirteen classic HGSCA, 19 classic LGSCA, and 19 IGSCA were selected for p53 and BRAF V600E IHC and molecular genetic testing by next-generation sequencing. IGSCA showed the architectural patterns of invasion of LGSCA, but with higher grade nuclear features focally and a mitotic index intermediate between LGSCA and HGSCA. Few cases in the IGSCA group showed mutant TP53 by IHC or sequencing (4/18, 22.2%), 1 case had mutant BRAF non-V600E by sequencing, and 1 had an NRAS mutation. When present, the mutations were identical in the low-grade and high-grade areas. The IGSCA group had a long-term survival similar to the classic HGSCA group. IGSCA with mixed morphologic features of HGSCA and LGSCA is a rare and potentially clinically aggressive variant of serous carcinoma. Their distinct morphologic, but heterogenous molecular features, including low frequency of TP53 and BRAF mutations suggest that these rare tumors may have a different pathogenesis pathway compared with classic HGSCA and classic LGSCA.

Background Breast cancer is the most common cancer and the leading cause of cancer mortality among Latinas. As more is learned about the association between mammographic breast density (MBD) and breast cancer risk, a number of U.S. states adopted legislation and now a federal law mandates written notification of MBD along with mammogram results. These notifications vary in content and readability, though, which may limit their effectiveness and create confusion or concern, especially among women with low health literacy or barriers to screening. The purpose of this study is to determine whether educational enhancement of MBD notification results in increased knowledge, decreased anxiety, and adherence to continued mammography screening among Latina women in a limited-resources setting. Methods Latinas LEarning About Density (LLEAD) is a randomized clinical trial (RCT) comparing the impact of three notification approaches on behavioral and psychological outcomes in Latina women. Approximately 2000 Latinas undergoing screening mammography in a safety-net community clinic will be randomized 1:1:1 to mailed notification (usual care); mailed notification plus written educational materials (enhanced); or mailed notification, written educational materials, plus verbal explanation by a promotora (interpersonal). The educational materials and verbal explanations are available in Spanish or English. Mechanisms through which written or verbal information influences future screening motivation and behavior will be examined, as well as moderating factors such as depression and worry about breast cancer, which have been linked to diagnostic delays among Latinas. The study includes multiple psychological measures (anxiety, depression, knowledge about MBD, perceived risk of breast cancer, worry, self-efficacy) and behavioral outcomes (continued adherence to mammography). Measurement time points include enrollment, 2–4 weeks post-randomization, and 1 and 2 years post-randomization. Qualitative inquiry related to process and outcomes of the interpersonal arm and cost analysis related to its implementation will be undertaken to understand the intervention’s delivery and transferability. Discussion Legislation mandating written MBD notification may have unintended consequences on behavioral and psychological outcomes, particularly among Latinas with limited health literacy and resources. This study has implications for cancer risk communication and will offer evidence on the potential of generalizable educational strategies for delivering information on breast density to Latinas in limited-resource settings. Trial registration ClinicalTrials.gov, NCT02910986. Registered on 21 September 2016. Items from the WHO Trial Registration Data Set can be found in this protocol.

Objective: Understanding gender differences in self-perception of health (SPH) and self-efficacy can inform the design of tailored programs to improve health behaviors. We aimed to assess gender-specific differences in SPH and self-efficacy for maintaining wellness habits at a work-place wellness center. Methods: A workplace wellness center member survey was conducted in 2016. Information about SPH and self-efficacy to maintain wellness habits was assessed. Data were analyzed to assess gender differences in SPH and self-efficacy. Results: The survey was completed by 2784 members (mean age, 49.2 years; 68.2% women). SPH was similar between genders despite more men reporting health problems such as hypertension, diabetes, high cholesterol, and cigarette smoking. Women had higher self-efficacy about maintaining healthy diet, but the difference was not clinically meaningful. Women had lower self-efficacy in their ability to maintain physical activity. Conclusions: In this large cohort of worksite wellness center members, men and women had similar self-perception of health despite higher disease burden among men. Women had lower self-efficacy in their ability to maintain physical activity level but similar self-efficacy for maintaining healthy diet. These differences may inform the design of tailored wellness programs to meet the needs of both genders.

Physicians play a key role in implementing health policy, and US physicians were split in their opinions about the Affordable Care Act (ACA) soon after its implementation began. We readministered elements of a prior survey of US physicians to a similar sample to understand how US physicians' opinions of the ACA may have changed over a crucial five-year implementation period (2012-17), and we compared responses across both surveys. Of the 1,200 physicians to whom we sent a survey in the summer of 2017, 489 responded (a response rate of 41 percent). A majority of respondents (60 percent) believed that the ACA had improved access to care and insurance, yet many (43 percent) felt that it had reduced the affordability of coverage. More physicians agreed in 2017 than in 2012 that the ACA "would turn United States health care in the right direction" (53 percent versus 42 percent), despite reporting perceived worsening in several practice conditions over the same time period. After we adjusted for specialty, political party affiliation, practice setting type, perceived social responsibility, age, and sex, we found that only political party affiliation was a significant predictor of support for the ACA in the 2017 results.

Purpose To assess changes in breast density (BD) awareness, knowledge, and attitudes among US women over a period of 5 years. Methods Using a probability-based web panel representative of the US population, we administered an identical BD survey in 2012 and 2017 to women aged 40 to 74 years. Results In 2017, 65.8% had heard of BD (versus 57.5% in 2012; P = .0002). BD awareness in both 2012 and 2017 was significantly associated with race, income, and education. Among women aware of BD in 2017, 76.5% had knowledge of BD’s relationship to masking (versus 71.5% in 2012; P = .04); 65.5% had knowledge of BD’s relationship to cancer risk (versus 58.5%; P = .009); and 47.3% had discussed BD with a provider (versus 43.1% in 2012; P = .13). After multivariable adjustment, residence in a state with BD legislation was associated in 2017 with knowledge of BD’s relationship to risk but not to masking. Most women wanted to know their BD (62.5% in 2017 versus 59.8% in 2012; P = .46); this information was anticipated to cause anxiety in 44.8% (versus 44.9% in 2012; P = .96); confusion in 35.9% (versus 43.0%; P = .002); and feeling informed in 89.7% (versus 90.4%; P = .64). Over three-quarters supported federal BD legislation in both surveys. Response rate to the 2017 survey was 55% (1,502 of 2,730) versus 65% (1,506 of 2,311) in 2012. Conclusion Although BD awareness has increased, important disparities persist. Knowledge of BD’s impact on risk has increased; knowledge about masking and BD discussions with providers have not. Most women want to know their BD, would not feel anxious or confused as a result of knowing, and would feel empowered to make decisions. The federal BD notification legislation presents an opportunity to improve awareness and knowledge and encourage BD conversations with providers.

Objectives Long-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA). Methods Histologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated. Results Follow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM). Conclusions Appropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.

Aims: Limited data exist on atypical lipomatous tumour (ALT)/well-differentiated liposarcoma (WDL) and de-differentiated liposarcoma (DDLPS) in children and young adults. Methods and results: Cases of ALT/WDL/DDLPS arising in patients aged

Supplemental Digital Content is available in the text., Background. The role of liver transplantation (LT) in the management of portopulmonary hypertension (POPH) is poorly understood. The aim of this study was to better understand provider attitudes and practice patterns regarding the management of patients with POPH and to assess the concordance between clinical practice and current guidelines. Methods. We performed a multicenter survey study of hepatologists and pulmonary hypertension (PH) physicians at US LT centers that performed >50 transplants per year. Survey responses are summarized as number (%). Associations were assessed using a Wilcoxon-rank sum, chi-square, or Fisher exact test, as appropriate. Results. Seventy-four providers from 35 centers were included. There was marked variability regarding screening practices, management, and attitudes. Forty-two percent responded that POPH nearly always or often improves with LT, and 15.5% reported that POPH rarely or never improves. In contrast to current guidelines, 50.7% agreed that treated POPH should be an indication for LT in patients with compensated cirrhosis. Hepatologists were more likely than PH physicians to agree that POPH should be an indication for LT (P = 0.02). Forty-nine percent of respondents thought that the current POPH Model for End-stage Liver Disease exception criteria should be modified, and management of patients with an elevated mean pulmonary arterial pressure and normal pulmonary vascular resistance differed from current policies. Conclusions. There is marked variability in provider attitudes and practice patterns regarding the management of POPH. This study highlights the need for prospective studies to inform practice and for improved implementation of practice guidelines in order to standardize care.

Regular physical activity has been shown to improve pregnancy outcomes. We sought to identify barriers to exercise during the first trimester of pregnancy. Five hundred forty-nine pregnant women in their first trimester rated barriers to exercise on a scale of 1 (not a barrier) to 5 (a huge barrier) and recorded physical activity (minutes/week). Women were placed into one of three classifications, nonexercisers (zero exercise), infrequent exercisers (p < .001). Focusing education and interventions on these barriers may help pregnant women achieve healthy exercise levels.