Metastatic Kaposi's Sarcoma with Perirectal Involvement Diagnosed with Endoscopic Ultrasound-Guided EchoBrush Cytology Sampling

AIDS-related Kaposi's sarcoma (KS) is a low-grade vascular tumor that occurs in association with human herpesvirus 8 infection. Here we report the case of a 21-year-old male with recently diagnosed cutaneous KS who presented with rectal bleeding and anal pruritus. Initial endoscopic evaluation was nondiagnostic. CT imaging showed diffuse lymphadenopathy including perirectal involvement which was suspicious for metastatic KS. Echoendoscopy with needle biopsies and EchoBrush sampling of the lymph nodes revealed spindle cells confirming metastatic KS. Treatment was initiated with liposomal doxorubicin resulting in rapid improvement of the skin lesions. After treatment completion, repeat CT imaging showed improved lymphadenopathy. No further rectal bleeding or perianal pruritus was reported. Although the EchoBrush has previously been used to aid in the diagnosis of pancreatic lesions, this report describes a novel use of EchoBrush to diagnose KS from perirectal lymph nodes

Interns are from Venus, consultants are from Mars: differential perception among clinicians

OBJECTIVE: To test for the presence of sex-based differences in perception (the notion that men and women "think" differently, and that differences in perception are biologically based) among healthcare professionals. DESIGN: Prospective survey. SETTING AND PARTICIPANTS: 90 medical personnel at a tertiary care hospital in Newcastle, NSW. INTERVENTION: Healthcare professionals were shown two pictures that could be interpreted as depicting either a young or an old person, and a word that could be seen as geometric shapes. MAIN OUTCOME MEASURES: The effects of sex, age, seniority, and specialisation in relation to the first impression of the image, the ability to change one\u27s perception, and the speed of perception. RESULTS: Contrary to popular opinion, male physicians were more likely to perceive the older figures, and just as likely as women to be able to change their perception. Surgeons and junior staff were more likely to see, as well as being faster to form, an impression requiring abstract thought, and were more able to change their perceptions. CONCLUSIONS: Traditional sex stereotypes do not apply to medical personnel, but other age-based stereotypes, and professional rivalries (medical versus surgical) may have some empiric basis

Exploring the feasibility and acceptability of a recovery-focused group therapy intervention for adults with bipolar disorder: trial protocol

Introduction Improving accessible, acceptable recovery-oriented service provision for people with bipolar disorder (BD) is an important priority. Mindfulness and acceptance-based cognitive and behavioural therapies (or ‘third -wave’ CBT) may prove fruitful due to the considerable overlap between these approaches and key features of personal recovery. Groups also confer therapeutic benefits consistent with personal recovery and may improve recovery-oriented service provision by adding another modality for accessing support. The primary objective of this trial is to explore the feasibility and acceptability of a new recovery-focused group therapy (RfGT) intervention for adults with BD. This is the first published feasibility assessment of a time-limited RfGTrecovery-focused group therapy intervention for BD. Methods/ analysis This protocol describes an open feasibility study, utilising a pre-treatment design versus post- treatment design and nested qualitative evaluation. Participants will be recruited from the Central Coast region of New South Wales, Australia, from primary care providers, specialist mental health services, non-government organisations and via self-referral. The primary outcomes are feasibility and acceptability as indexed by recruitment, retention, intervention adherence, adverse events (if any) and detailed consumer feedback. Clinical outcomes and process measures will be assessed to inform future research. Primary outcome data will utiliseuse descriptive statistics (eg, summarizingsummarising recruitment, demographics, attendance, attrition and intervention adherence). Secondary outcomes will be assessed using repeated-measures analysis of covariance across all time points (including change, effect size and variability). Ethics and dissemination Ethical approval has been granted by the Northern Sydney Local Health District HREChuman research ethics committee (HREC) (HREC/16/HAWKE/69) and The University of Newcastle HREC (H-2016–0107). The Ffindings will be used to improve the intervention per user needs and preferences, and inform what amendments and/or information are required before a follow-on trial would be possible. This study contributes to a growing body of innovative, recovery-oriented innovations of psychological treatments for adults with BD.Dr Beck is supported by a stipend from the NHMRC Centre for Research Excellence in Mental Health and Substance Use (APP1041129; G1200943). In-kind support (therapy room) is provided by the R.E.A.D. Clinic. Dr Banfield is supported by Australian Research Council Discovery Early Career Researcher Award DE150100637

Clinical outcomes of patients with advanced synovial sarcoma or myxoid/round cell liposarcoma treated at major cancer centers in the United States

BACKGROUND: Outcomes data regarding advanced synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are limited, consisting primarily of retrospective series and post hoc analyses of clinical trials. METHODS: In this multi-center retrospective study, data were abstracted from the medical records of 350 patients from nine sarcoma centers throughout the United States and combined into a registry. Patients with advanced/unresectable or metastatic SS (n = 249) or MRCL (n = 101) who received first-line systemic anticancer therapy and had records of tumor imaging were included. Overall survival (OS), time to next treatment, time to distant metastasis, and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox regression. RESULTS: At start of first-line systemic anticancer therapy, 92.4% of patients with SS and 91.1% of patients with MRCL had metastatic lesions. However, 74.7% of patients with SS and 72.3% of patients with MRCL had ≥2 lines of systemic therapy. Median OS and median PFS from first-line therapy for SS was 24.7 months (95% CI, 20.9-29.4) and 7.5 months, respectively (95% CI, 6.4-8.4). Median OS and median PFS from start of first-line therapy for MRCL was 29.9 months (95% CI, 27-44.6) and 8.9 months (95% CI 4.5-12.0). CONCLUSIONS: To the best of our knowledge, this is the largest retrospective study of patients with SS and MRCL. It provides an analysis of real-world clinical outcomes among patients treated at major sarcoma cancer centers and could inform treatment decisions and design of clinical trials. In general, the survival outcomes for this selected population appear more favorable than in published literature

Expert consensus on re-irradiation for current glioma

Source at http://doi.org/10.1186/s13014-017-0928-3Purpose:To investigate radiation oncologists’ opinions on important considerations to offering re-irradiation (re-RT) as a treatment option for recurrent glioma.Materials and methods:A survey was conducted with 13 radiation oncologists involved in the care of central nervous system tumor patients. The survey was comprised of 49 questions divided into 2 domains: a demographic section (10 questions) and a case section (5 re-RT cases with 5 to 6 questions representing one or several re-RT treatment dilemmas as may be encountered in the clinic). Respondents were asked to rate the relevance of various factors to offering re-RT, respond to the cases with a decision to offer re-RT vs. not, volume to be treated, margins to be employed, dose/fractionation suggested and any additional comments with respect to rationale in each scenario.Results:Sixty nine percent of responders have been practicing for greater than 10 years and 61% have re-RT 20 to 100 patients to date, with 54% seeing 2–5 re-RT cases per month and retreating 1–2 patients per month. Recurrent tumor volume, time since previous radiation therapy, previously administered dose to organs at risk and patient performance status were rated by the majority of responders (85%, 92%, 77%, and 69% respectively) as extremely relevant or very relevant to offering re-RT as an option.Conclusion:The experts’ practice of re-RT is still heterogeneous, reflecting the paucity of high-quality prospective data available for decision-making. Nevertheless, practicing radiation oncologists can support own decisions by referring to the cases found suitable for re-RT in this survey

Health-related quality of life and pain with selinexor in patients with advanced dedifferentiated liposarcoma

[Objective] Compare health-related quality of life (HRQoL) of selinexor versus placebo in patients with dedifferentiated liposarcoma.[Materials & methods] HRQoL was assessed at baseline and day 1 of each cycle using the European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire. Results were reported from baseline to day 169 (where exposure to treatment was maximized while maintaining adequate sample size).[Results] Pain scores worsened for placebo versus selinexor across all postbaseline visits, although differences in HRQoL at some visits were not significant. Other domains did not exhibit significant differences between arms; however, scores in both arms deteriorated over time.[Conclusion] Patients treated with selinexor reported lower rates and slower worsening of pain compared with patients who received placebo.This study was funded by Karyopharm Therapeutics, Inc. M Gounder: reports an institutional research grant from Karyopharm, personal fees from Karyopharm, Epizyme, Springworks, Daiichi, Bayer, Amgen, Tracon, Flatiron, Medscape, Physicians Education Resource, Guidepoint, GLG and UpToDate; and grants from the National Cancer Institute, National Institutes of Health (P30CA008748) – core grant (CCSG shared resources and core facility). ARA Razak: consulting/Ad board: Merck & Adaptimmune Research support: Karyopharm Therapeutics, Deciphera, Blueprint Medicines, Pfizer, Adaptimmune, Merck, Roche/Genentech, Bristol-Myers Squibb, Medimmune, Amgen, GSK, AbbVie, Iterion Therapeutics. AM Gilligan: employee of Karyopharm Therapeutics, Inc. H Leong: employee of Karyopharm Therapeutics, Inc. X Ma: employee of Karyopharm Therapeutics, Inc. N Somaiah: consultant for Deciphera, Blueprint, Bayer Research Support from Ascentage, Astra-Zeneca, Daiichi-Sankyo, Deciphera, Eli Lilly, Karyopharm and GSK. SP Chawla: consultant for Amgen, Roche, GlaxoSmithKline, Threshold Pharmaceuticals, CytRx Corporation, Ignyta, Immune Design, TRACON Pharma, Karyopharm Therapeutics, SARC: Sarcoma Alliance for Research though Collaboration, Janssen, Advenchen Laboratories, Bayer, NKMax, InhibRx. Grants or contracts from Amgen, Roche, GlaxoSmithKline, Threshold Pharmaceuticals, CytRx Corporation, Ignyta, Immune Design, TRACON Pharma, Karyopharm Therapeutics, SARC: Sarcoma Alliance for Research though Collaboration, Janssen, Advenchen Laboratories, Bayer, InhibRx, NKMax. G Grignani: consultant for Eli Lilly, Novartis, Glaxo, Pharmamar, EISAI, Bayer, Merck. SM Schuetze: consultant – NanoCarrier, UpToDate. Research funding to institution – Adaptimmune, Amgen, Blueprint, Glaxo-SmithKline, Karyopharm. B Vincenzi: Consultant for Pharmamar Eisai, Lilly, Abbott, Novartis, Accord AJ Wagner: consultant for Daiichi-Sankyo, Deciphera, Eli Lilly, Epizyme, NovoCarrier, Mundipharma, and Research Support to My Institution from Aadi Bioscience, Daiichi-Sankyo, Deciphera, Eli Lilly, Karyopharm and Plexxikon. RL Jones: consultant for Adaptimmune, Athenex, Bayer, Boehringer Ingelheim, Blueprint, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immunedesign, Lilly, Merck, Pharmamar, Springworks, Tracon, Upto Date. J Shah: employee of Karyopharm Therapeutics, Inc. S Shacham: employee of Karyopharm Therapeutics, Inc. M Kauffman: employee of Karyopharm Therapeutics, Inc. RF Riedel: ownership - Limbguard, LLC (Spouse); Institutional Clinical Research Support - AADi, AROG, Blueprint, Daiichi-Sankyo, Deciphera, Glaxo-SmithKline, Karyopharm, Ignyta, Immune Design, NanoCarrier, Oncternal, Philogen, Plexxikon, Roche, Springworks, Tracon; Consultant/Advisor - Bayer, Blueprint, Daiichi-Sankyo, Deciphera, Ignyta, NanoCarrier. S Attia: reports research funding from Desmoid Tumor Research Foundation and research funding to their institution from: AB Science, TRACON Pharma, Bayer, Novartis, Lilly, Immune Design, Karyopharm Therapeutics, Epizyme, Blueprint Medicines, Genmab, CBA Pharma, Merck, Philogen, Gradalis, Deciphera, Takeda, Incyte, Springworks, Adaptimmune, Advenchen Laboratories, Bavarian Nordic, BTG, PTC Therapeutics, GlaxoSmithKline, FORMA Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Peer reviewe

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intention—thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world

Epilepsy Personal Assistant Device-A Mobile Platform for Brain State, Dense Behavioral and Physiology Tracking and Controlling Adaptive Stimulation

Epilepsy is one of the most common neurological disorders, and it affects almost 1% of the population worldwide. Many people living with epilepsy continue to have seizures despite anti-epileptic medication therapy, surgical treatments, and neuromodulation therapy. The unpredictability of seizures is one of the most disabling aspects of epilepsy. Furthermore, epilepsy is associated with sleep, cognitive, and psychiatric comorbidities, which significantly impact the quality of life. Seizure predictions could potentially be used to adjust neuromodulation therapy to prevent the onset of a seizure and empower patients to avoid sensitive activities during high-risk periods. Long-term objective data is needed to provide a clearer view of brain electrical activity and an objective measure of the efficacy of therapeutic measures for optimal epilepsy care. While neuromodulation devices offer the potential for acquiring long-term data, available devices provide very little information regarding brain activity and therapy effectiveness. Also, seizure diaries kept by patients or caregivers are subjective and have been shown to be unreliable, in particular for patients with memory-impairing seizures. This paper describes the design, architecture, and development of the Mayo Epilepsy Personal Assistant Device (EPAD). The EPAD has bi-directional connectivity to the implanted investigational Medtronic Summit RC+S-TM device to implement intracranial EEG and physiological monitoring, processing, and control of the overall system and wearable devices streaming physiological time-series signals. In order to mitigate risk and comply with regulatory requirements, we developed a Quality Management System (QMS) to define the development process of the EPAD system, including Risk Analysis, Verification, Validation, and protocol mitigations. Extensive verification and validation testing were performed on thirteen canines and benchtop systems. The system is now under a first-in-human trial as part of the US FDA Investigational Device Exemption given in 2018 to study modulated responsive and predictive stimulation using the Mayo EPAD system and investigational Medtronic Summit RC+S-TM in ten patients with non-resectable dominant or bilateral mesial temporal lobe epilepsy. The EPAD system coupled with an implanted device capable of EEG telemetry represents a next-generation solution to optimizing neuromodulation therapy

The relevance of rich club regions for functional outcome post-stroke is enhanced in women

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and similar to 3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich dub regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.Peer reviewe