tbuckley/cabot-search huggingface dataset:
Transjugular intrahepatic portosystemic stent-shunt in the management of portal hypertension
Authors: Dhiraj Tripathi, Adrian J Stanley, Peter C Hayes, Simon Travis, Matthew J Armstrong, Emmanuel A Tsochatzis, Ian A Rowe, Nicholas Roslund, Hamish Ireland, Mandy Lomax, Joanne A Leithead, Homoyon Mehrzad, Richard J Aspinall, Joanne McDonagh, David Patch
Journal: Gut (2020)

These guidelines on transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the Liver Section of the BSG. The guidelines are new and have been produced in collaboration with the British Society of Interventional Radiology (BSIR) and British Association of the Study of the Liver (BASL). The guidelines development group comprises elected members of the BSG Liver Section, representation from BASL, a nursing representative and two patient representatives. The quality of evidence and grading of recommendations was appraised using the GRADE system. These guidelines are aimed at healthcare professionals considering referring a patient for a TIPSS. They comprise the following subheadings: indications; patient selection; procedural details; complications; and research agenda. They are not designed to address: the management of the underlying liver disease; the role of TIPSS in children; or complex technical and procedural aspects of TIPSS.
Development and Validation of a Machine Learning Individualized Treatment Rule in First-Episode Schizophrenia
Authors: Chi-Shin Wu, Alex R. Luedtke, Ekaterina Sadikova, Hui-Ju Tsai, Shih-Cheng Liao, Chen-Chung Liu, Susan Shur-Fen Gau, Tyler J. VanderWeele, Ronald C. Kessler
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Little guidance exists to date on how to select antipsychotic medications for patients with first-episode schizophrenia. <h3>Objective</h3> To develop a preliminary individualized treatment rule (ITR) for patients with first-episode schizophrenia. <h3>Design, Setting, and Participants</h3> This prognostic study obtained data from Taiwan's National Health Insurance Research Database on patients with prescribed antipsychotic medications, ambulatory claims, or discharge diagnoses of a schizophrenic disorder between January 1, 2005, and December 31, 2011. An ITR was developed by applying a targeted minimum loss–based ensemble machine learning method to predict treatment success from baseline clinical and demographic data in a 70% training sample. The model was validated in the remaining 30% of the sample. The probability of treatment success was estimated for each medication for each patient under the model. The analysis was conducted between July 16, 2018, and July 15, 2019. <h3>Exposures</h3> Fifteen different antipsychotic medications. <h3>Main Outcomes and Measures</h3> Treatment success was defined as not switching medication and not being hospitalized for 12 months. <h3>Results</h3> Among the 32 277 patients in the analysis, the mean (SD) age was 36.7 (14.3) years, and 15 752 (48.8%) were male. In the validation sample, the treatment success rate (SE) was 51.7% (1.0%) under the ITR and was 44.5% (0.5%) in the observed population (<i>Z</i> = 7.1;<i>P</i> &lt; .001). The estimated treatment success if all patients were given a prescription for 1 medication was significantly lower for each of the 13 medications than under the ITR (<i>Z</i> = 4.2-16.8; all<i>P</i> &lt; .001). Aripiprazole (3088 [31.9%]) and amisulpride (2920 [30.2%]) were the medications most often recommended by the ITR. Only 1054 patients (10.9%) received ITR-recommended medications. Observed treatment success, although lower than the success under the ITR, was nonetheless significantly higher than if medications had been randomized (44.5% [SE, 0.55%] vs 41.3% [SE, 0.4%];<i>Z</i> = 6.9;<i>P</i> &lt; .001), although only marginally higher than if medications had been randomized in their observed population proportions (44.5% [SE, 0.5%] vs 43.5% [SE, 0.4%];<i>Z</i> = 2.2;<i>P</i> = .03]). <h3>Conclusions and Relevance</h3> These results suggest that an ITR may be associatded with an increase in the treatment success rate among patients with first-episode schizophrenia, but experimental evaluation is needed to confirm this possibility. If confirmed, model refinement that investigates biomarkers, clinical observations, and patient reports as additional predictors in iterative pragmatic trials would be needed before clinical implementation.
Genomic alterations and tumor mutational features of Chinese Xp11.2 translocation renal cell carcinoma patients.
Authors: Yuan-Yuan Qu, Hailiang Zhang, Wenhao Xu, Hongkai Wang, Xi Tian, Dalong Cao, Yueting Qu, Guohai Shi, Dingwei Ye
Journal: Journal of Clinical Oncology (2020)

736 Background: Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) is a rare subtype of RCC which occurs predominantly in children and adolescents. Xp11.2 RCC is characterized by the gene fusions of transcription factor E3 (TFE3). Since there is a high false-positive and false-negative rate of immunohistochemistry (IHC) for TFE3 and an uncertainty of TFE3 fusion partners by fluorescence in situ hybridization (FISH), a genetic approach, such as DNA sequencing, is necessary for auxiliary diagnosis. Methods: Thirty Chinese Xp11.2 RCC patients with positive TEF3 fusion diagnosed by FISH were involved in this analysis. Formalin-fixed, paraffin-embedded (FFPE) samples were collected for a next-generation sequencing (NGS)-based 576 gene panel assay. Genomic alterations including single base substitution, copy number variations, gene fusions, and rearrangements were assessed. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were also analyzed by an NGS algorithm. Results: The 30 patients in the Xp11.2 RCC cohort included 13 males and 17 females, and had a median age of 30 years. TFE3 fusions of these patients were confirmed by both FISH and NGS. Out of the 30 Xp11.2 RCC patients, 2 patients (6.7%) showed negative TFE3 IHC expression and 4 patients (13.3%) showed equivocal TFE3 IHC expression. ASPL (9/30), PRCC (5/30), PSF (5/30), and NONO (3/30) were the most common partners of TFE3 fusion in this cohort. Moreover, we identified uncommon or novel partner genes by NGS, including ZNF627 (1/30), PTPN12 (1/30), PBM10 (1/30), PARP14 (1/30), MED15 (2/30), MATR3 (1/30), LUC7L3 (1/30), KHSRP (1/30), and EWSR1 (1/30). Based on the NGS results, several actionable genomic alterations including CDKN2A, BRCA2, and ATM were found in this study. All samples were identified as microsatellite stable (MSS). The median TMB of the entire cohort was 1.35 muts/Mb (range, 0-9.2 muts/Mb). Conclusions: In summary, we identified the partner genes of TFE3 fusion in 30 Chinese Xp11.2 RCC patients by NGS. Ten uncommon or novel partner genes (33.3%) of TFE3 were identified in this study. Overall, our results provide evidence for diagnosis and therapeutic strategies for Xp11.2 RCC patients.
Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L)
Authors: Ryoji Kato, Hidetoshi Hayashi, Yasutaka Chiba, Eriko Miyawaki, Junichi Shimizu, Tomohiro Ozaki, Daichi Fujimoto, Ryo Toyozawa, Atsushi Nakamura, Toshiyuki Kozuki, Kentaro Tanaka, Shunsuke Teraoka, Kazuhiro Usui, Kazumi Nishino, Osamu Hataji, Keiichi Ota, Noriyuki Ebi, Sho Saeki, Yuki Akazawa, Motoyasu Okuno, Nobuyuki Yamamoto, Kazuhiko Nakagawa
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Studies have suggested that chemotherapy after immune checkpoint inhibitors may confer an improved response for non–small cell lung cancer (NSCLC). However, potential selection bias in such studies has not been addressed. We therefore applied propensity score analysis to investigate the efficacy of chemotherapy after PD-1 inhibitor treatment (CAP) compared with chemotherapy alone. Methods We conducted a retrospective observational cohort study for patients treated at 47 institutions across Japan between April 1, 2014 and July 31, 2017. Eligible patients had advanced or recurrent NSCLC who have undergone chemotherapy. Patients subsequently treated with chemotherapy (docetaxel with or without ramucirumab, S-1 or pemetrexed) either after PD-1 inhibitor therapy (CAP cohort) or alone (control cohort) were included. The primary end point was objective response rate (ORR). Inverse probability weighting (IPW) was applied to adjust for potential confounding factors. Results A total of 1439 patients (243 and 1196 in the CAP and control cohorts, respectively) was available for unadjusted analysis. Several baseline characteristics—including age, histology, EGFR or ALK genetic alterations, and brain metastasis—differed significantly between the two cohorts. After adjustment for patient characteristics with the IPW method, ORR was 18.9% for the CAP cohort and 11.0% for the control cohort (ORR ratio 1.71; 95% CI 1.19 to 2.46; p=0.004). IPW-adjusted Kaplan-Meier curves showed that median progression-free survival (PFS) for the CAP and control cohorts was 2.8 and 2.7 months (IPW-adjusted HR 0.95; 95% CI 0.80 to 1.12; p=0.55), and median overall survival (OS) was 9.2 and 10.4 months (IPW-adjusted HR 1.05; 95% CI 0.86 to 1.28; p=0.63), respectively. Conclusions After accounting for selection bias by propensity score analysis, CAP showed a significantly higher ORR compared with chemotherapy alone, with the primary end point of ORR being achieved. However, these results did not translate into a PFS or OS advantage, suggesting that prior administration of PD-1 inhibitors may result in a synergistic antitumor effect with subsequent chemotherapy, but that such an effect is transient. CAP therefore does not appear to achieve durable tumor control or confer a lasting survival benefit.
Screening for Trypanosoma cruzi infection in immigrants and refugees: Systematic review and recommendations from the Spanish Society of Infectious Diseases and Clinical Microbiology
Authors: María Velasco, Luis Andrés Gimeno-Feliú, Israel Molina, Joaquín Salas-Coronas, Ivan Solà, Begoña Monge-Maillo, Diego Torrús-Tendero, Joan Caylà, Ena Niño de Guzmán, JL Pérez Arellano, Jose A Pérez-Molina
Journal: Eurosurveillance (2020)

Background Chagas disease has spread beyond its original borders on the American continent with migration. It can be transmitted from mother to child, through organ transplantation and transfusion of blood and blood products. It is necessary to determine when to screen for this infection. Aim Our objective was to evaluate the appropriateness of screening for Trypanosoma cruzi infection in Latin American migrants and their descendants. Methods We reviewed the literature using rigorous criteria. The quality of evidence was ranked according to the GRADE classification. An evidence to decision framework was adopted to provide information on the most relevant aspects necessary to formulate recommendations. Results The 33 studies evaluated revealed a prevalence of T. cruzi infection among Latin American migrants in Europe of 6.08% (95% confidence interval (CI): 3.24–9.69; 28 studies). Vertical transmission occurred in three of 100 live births (95% CI: 1–6; 13 studies). The prevalence of cardiovascular disease was 19% (95% CI: 13–27; nine studies), including only 1% severe cardiac events (95% CI: 0–2; 11 studies). The overall quality of evidence was low because of risk of bias in the studies and considerable heterogeneity of the evaluated populations. The recommendations took into account economic studies on the value of screening strategies and studies on acceptability of screening and knowledge of the disease in the affected population. Conclusions We identified five situations in which screening for T. cruzi infection is indicated. We recommend screening persons from endemic areas and children of mothers from these areas.
A phase Ib study of combination of avelumab and taxane-based chemotherapy in platinum refractory or ineligible metastatic urothelial cancer (AVETAX study).
Authors: Rohan Garje, Timothy Ginader, Douglas Earl Laux, Kenneth Gerard Nepple, Mohammed M. Milhem, Michael A. O'Donnell, Yousef Zakharia
Journal: Journal of Clinical Oncology (2020)

487 Background: Advanced bladder cancer is the most common malignancy of the urinary system with 5-year OS rates of 5-7%. Platinum based chemotherapy and checkpoint inhibitors are currently available treatment options but with limited benefit. We hypothesize that combining Avelumab (anti-PD-L1 immunotherapy) with Docetaxel is safe and will lead to cancer cell death releasing neoantigens with enhanced anti-tumor immune mediated cytotoxicity. Methods: This is a phase 1b, single arm, non-randomized, open label prospective clinical trial to evaluate the combination of Avelumab and Docetaxel in adult subjects with locally advanced or metastatic urothelial carcinoma with disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. It has two phases: Phase 1b dose de-escalation of docetaxel (Level 0: 75, Level -1: 60 or Level -2: 45 mg/m2) with standard dose avelumab (10 mg/kg) to establish phase 2 dose in the standard 3+3 design. In the dose expansion phase, the phase 2 dose of docetaxel with avelumab will be evaluated for efficacy. The combination therapy is administered every 3 weeks for 6 cycles and then avelumab alone is continued every 2 weeks. Primary endpoint is safety. Efficacy endpoints include objective response rate, progression free survival and overall survival. Results: At the cutoff date of 10/21/2019, 10 eligible patients were enrolled in the study. Only one of the six patients treated with level 0 dose of docetaxel had a dose limiting toxicity (neutropenic fever). Docetaxel at 75 mg/m2 along the avelumab was deemed safe for dose expansion cohort. Additional 4 patients were enrolled in the dose expansion cohort. Efficacy data is preliminary with 1 patient achieving CR, 2 pts had PR, 2 pts had SD, 1 pt PD and 4 pts are not yet evaluable. The most common Grade 3 or 4 AEs were febrile neutropenia, urinary tract infection and confusion. No treatment related deaths were noted. Conclusions: The combination of docetaxel in combination with avelumab is safe and the preliminary data showed promising efficacy, further data to be presented at the meeting. Clinical trial information: NCT03575013.
Royal College of Pathologists: president elect is barred after misconduct allegations are upheld
Authors: Clare Dyer
Journal: BMJ (2020)

The Royal College of Pathologists has barred its president elect, Peter Furness, from taking office after a disciplinary panel convened by the college upheld allegations of misconduct against him.

Furness, 64, who was due to take over as president in November, is a consultant histopathologist at Leicester Royal Infirmary and honorary professor of renal pathology at Leicester University. He ran for the presidency and was elected on a platform that argued that “the college should cut back to its core function of defining and maintaining quality.” He had previously served as president from 2008 to 2011.

It was only when he left office after the first term “that I realised how excessively our …
Executive Function and Psychopathology: A Neurodevelopmental Perspective
Authors: Philip David Zelazo
Journal: Annual Review of Clinical Psychology (2020)

Executive function (EF) skills are neurocognitive skills that support the reflective, top-down coordination and control of other brain functions, and there is neural and behavioral evidence for a continuum from more “cool” EF skills activated in emotionally neutral contexts to more “hot” EF skills needed for the reversal of motivationally significant tendencies. Difficulties in EF are transdiagnostic indicators of atypical development. A neurodevelopmental model traces the pathway from adverse childhood experiences and stress to disruption of the development of neural systems supporting reflection and EF skills to an increased risk for general features of psychopathology. Research indicates that EF skills can be cultivated through scaffolded training and are a promising target for therapeutic and preventive intervention. Intervention efficacy can be enhanced by mitigating disruptive bottom-up influences such as stress, training both hot and cool EF skills, and adding a reflective, metacognitive component to promote far transfer of trained skills.
Severe eosinophilic asthma with nasal polyposis: A phenotype for improved sinonasal and asthma outcomes with mepolizumab therapy
Authors: Peter Howarth, Geoffrey Chupp, Linda M. Nelsen, Eric S. Bradford, Daniel J. Bratton, Steven G. Smith, Frank C. Albers, Guy Brusselle, Claus Bachert
Journal: Journal of Allergy and Clinical Immunology (2020)
Applicability of Skin Tape Stripping Methodology In Conjunction With LC-MS/MS To Detect Topical Emollients and Drugs Used in Atopic Dermatitis
Authors: Evgeny Berdyshev, Irina Bronova, Anna Sofia Bronoff, John Jung, Kari Nadeau, Elena Goleva, Donald Leung
Journal: Journal of Allergy and Clinical Immunology (2020)
Exploring motivation to pursue genomic profiling among patients with metastatic genitourinary cancers.
Authors: Errol James Philip, Cristiane Decat Bergerot, Paulo Gustavo Bergerot, Meghan Salgia, Nicholas Salgia, Nazli Dizman, Joann Hsu, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2020)

663 Background: Genomic profiling (GP) is becoming more widespread in oncologic care, yet little is known regarding patients’ motivations to pursue or accept such testing. The current study examined patients’ reasons to pursue GP in the context of advanced genitourinary disease, and their potential association with demographic characteristics and psychiatric symptoms (anxiety and depression). Methods: Patients were recruited from a single institution after receiving a standardized dialogue about GP from their oncologist. Patients were included if they had received GP in the context of routine clinical care. Patients’ reasons for pursuing GP were assessed, as well as anxiety and depression via the PROMIS measures. The Kruskal-Wallis test was used. Results: A cohort of 90 patients (median 64 years old; 76% male; 71% white) with metastatic genitourinary cancers (61% renal cell carcinoma, 22% urothelial carcinoma and 17% prostate cancer) were enrolled. Demographic characteristics and psychosocial symptoms were associated with the pursuit of GP. Older and female patients tended to report that their physician’s recommendation was a primary driver of their decision (p&lt;0.05), while younger patients sought to avoid unnecessary treatment and side-effects (p=0.04). In addition, patients experiencing anxiety and depression reported that GP adoption was driven by a desire to predict disease outcomes (p&lt;0.05). Conclusions: The current study provides novel insight into the motivations underlying patients’ adoption of GP. The importance of a physicians’ recommendation may be indicative of the lasting influence of a paternalistic model of care, while the desire to avoid of side-effects can help guide effective discussions concerning the role of GP in care planning. The association between anxiety/depression and the hope that GP can predict disease outcomes reinforces the importance of ensuring patients possess an accurate understanding of this testing paradigm.
Assessment of Tree-Based Statistical Learning to Estimate Optimal Personalized Treatment Decision Rules for Traumatic Finger Amputations
Authors: Kelly A. Speth, Alfred P. Yoon, Lu Wang, Kevin C. Chung
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Optimal treatment for traumatic finger amputation is unknown to date. <h3>Objective</h3> To use statistical learning methods to estimate evidence-based treatment assignment rules to enhance long-term functional and patient-reported outcomes in patients after traumatic amputation of fingers distal to the metacarpophalangeal joint. <h3>Design, Setting, and Participants</h3> This decision analytical model used data from a retrospective cohort study of 338 consenting adult patients who underwent revision amputation or replantation at 19 centers in the United States and Asia from August 1, 2016, to April 12, 2018. Of those, data on 185 patients were included in the primary analysis. <h3>Exposures</h3> Treatment with revision amputation or replantation. <h3>Main Outcomes and Measures</h3> Outcome measures were hand strength, dexterity, hand-related quality of life, and pain. A tree-based statistical learning method was used to derive clinical decision rules for treatment of traumatic finger amputation. <h3>Results</h3> Among 185 study participants (mean [SD] age, 45 [16] years; 156 [84%] male), the median number of fingers amputated per patient was 1 (range, 1-5); 115 amputations (62%) were distal to the proximal interphalangeal joint, and 110 (60%) affected the nondominant hand. On the basis of the tree-based statistical learning estimates, to maximize hand dexterity or to minimize patient-reported pain, replantation was found to be the best strategy. To maximize hand strength, revision amputation was the best strategy for patients with a single-finger amputation but replantation was preferred for all other injury patterns. To maximize patient-reported quality of life, revision amputation was the best approach for patients with dominant hand injuries, and replantation was the best strategy for patients with nondominant hand injuries. <h3>Conclusions and Relevance</h3> The findings suggest that the approach to treating traumatic finger amputations varies based on the patient’s injury characteristics and functional needs.
Natural History of Cognitive Impairment in Critical Illness Survivors. A Systematic Review
Authors: Kimia Honarmand, Rajkamal S. Lalli, Fran Priestap, Jennifer L. Chen, Christopher W. McIntyre, Adrian M. Owen, Marat Slessarev
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Long-term cognitive impairment is common among ICU survivors, but its natural history remains unclear. In this systematic review, we report the frequency of cognitive impairment in ICU survivors across various time points after ICU discharge that were extracted from 46 of the 3,350 screened records. Prior studies used a range of cognitive instruments, including subjective assessments (10 studies), single or screening cognitive test such as Mini-Mental State Examination or Trail Making Tests A and B (23 studies), and comprehensive cognitive batteries (26 studies). The mean prevalence of cognitive impairment was higher with objective rather than subjective assessments (54% [95% confidence interval (CI), 51–57%] vs. 35% [95% CI, 29–41%] at 3 months after ICU discharge) and when comprehensive cognitive batteries rather than Mini-Mental State Examination were used (ICU discharge: 61% [95% CI, 38–100%] vs. 36% [95% CI, 15–63%]; 12 months after ICU discharge: 43% [95% CI, 10–78%] vs. 18% [95% CI, 10–20%]). Patients with acute respiratory distress syndrome had higher prevalence of cognitive impairment than mixed ICU patients at ICU discharge (82% [95% CI, 78–86%] vs. 48% [95% CI, 44–52%]). Although some studies repeated tests at more than one time point, the time intervals between tests were arbitrary and dictated by operational limitations of individual studies or chosen cognitive instruments. In summary, the prevalence and temporal trajectory of ICU-related cognitive impairment varies depending on the type of cognitive instrument used and the etiology of critical illness. Future studies should use modern comprehensive batteries to better delineate the natural history of cognitive recovery across ICU patient subgroups and determine which acute illness and treatment factors are associated with better recovery trajectories.
X-linked agammaglobulinemia (XLA) clinical profile
Authors: Fernanda Vaz, Luiza Marino, Isabella Manhães, Marilia Moraes, Rafael Saldanha, Raissa Anjos-Roque, Pedro Bubach, Nathalia Vital, Caroline Ferreira, Mariana Pimentel, Carolina Aranda, Dirceu Sole
Journal: Journal of Allergy and Clinical Immunology (2020)