tbuckley/cabot-search huggingface dataset:
Association of an Early Intervention Service for Psychosis With Suicide Rate Among Patients With First-Episode Schizophrenia-Spectrum Disorders
Authors: Sherry Kit Wa Chan, Stephanie Wing Yan Chan, Herbert H. Pang, Kang K. Yan, Christy Lai Ming Hui, Wing Chung Chang, Edwin Ho Ming Lee, Eric Yu Hai Chen
Journal: JAMA Psychiatry (2018)

<h3>Importance</h3> Patients with schizophrenia have a substantially higher suicide rate than the general public. Early intervention (EI) services improve short-term outcomes. However, little is known about the association of EI with suicide reduction in the long term. <h3>Objective</h3> To examine the association of a 2-year EI service with suicide reduction in patients with first-episode schizophrenia-spectrum (FES) disorders during 12 years and the risk factors for early and late suicide. <h3>Design, Setting, and Participants</h3> This historical control study compared 617 consecutive patients with FES who received the 2-year EI service in Hong Kong between July 1, 2001, and June 30, 2003, with 617 patients with FES who received standard care (SC) between July 1, 1998, and June 30, 2001, matched individually. Clinical information was systematically retrieved for the first 3 years of clinical care for both groups. The details of death were collected up to 12 years from presentation to the services. Data analysis was performed from October 30, 2016, to August 18, 2017. <h3>Main Outcomes and Measures</h3> Suicide rate during 12 years was the primary measure. The association of the EI service with the suicide rates during years 1 through 3 and years 4 through 12 were explored separately. <h3>Results</h3> The main analysis included 1234 patients, with 617 in each group (mean [SD] age at baseline, 21.2 [3.4] years in the EI group and 21.3 [3.4] years in the SC group; 318 male [51.5%] in the EI group and 322 [52.2%] in the SC group). The suicide rates were 7.5% in the SC group and 4.4% in the EI group (McNemar χ<sup>2</sup> = 5.55,<i>P</i> = .02). Patients in the EI group had significantly better survival (propensity score–adjusted hazard ratio, 0.57; 95% CI, 0.36-0.91;<i>P</i> = .02), with the maximum association observed in the first 3 years. The number of suicide attempts was an indicator of early suicide (1-3 years). Premorbid occupational impairment, number of relapses, and poor adherence during the initial 3 years were indicators of late suicide (4-12 years). <h3>Conclusions and Relevance</h3> This study suggests that the EI service may be associated with reductions in the long-term suicide rate. Suicide at different stages of schizophrenia was associated with unique risk factors, highlighting the importance of a phase-specific service.
Phase 2 multicenter study of the EZH2 inhibitor tazemetostat in adults with synovial sarcoma (NCT02601950).
Authors: Patrick Schoffski, Mark Agulnik, Silvia Stacchiotti, Lara Emily Davis, Victor Manuel Villalobos, Antoine Italiano, Suzanne George, Gregory Michael Cote, Stephen Blakemore, Alicia Clawson, Scott Daigle, Scott Ribich, Maria Roche, Jill Rodstrom, Peter T.C. Ho, Mrinal M. Gounder
Journal: Journal of Clinical Oncology (2017)

11057 Background: Synovial sarcoma (SS) accounts for 5-10% of all soft tissue sarcomas (STS). Metastatic and/or locally advanced disease occurs in up to 70% of patients (pts), with reported median overall survival (OS) as short as 22 months. SS18-SSX translocations, a defining molecular feature of SS, generate a fusion protein that competes with native SS18 during SWI/SNF complex assembly disrupting complex function. SWI/SNF complexes containing the fusion protein lack INI1 and cellular INI1 expression levels are reduced to varying degrees in SS. This mechanism of INI1 reduction is distinct to that observed in malignant rhabdoid tumors, epithelioid sarcoma or other INI1 negative tumors. Tazemetostat, a potent and selective EZH2 inhibitor, has demonstrated activity in preclinical SS models with the proposed mechanism of sensitivity being via INI1 reduction inducing compromised SWI/SNF activity and tumor dependence on EZH2. Methods: This is a phase 2 multicenter open-label non-randomized study with 5 cohorts of different tumor types with INI1 loss/reduction or evidence of SS18 rearrangement. Adult pts in the SS cohort were treated with tazemetostat (800 mg po BID). Up to 30 pts were enrolled using a 2-stage Green-Dahlberg design. The primary endpoint is complete response, partial response or stable disease (SD) at 16 wks. Success at the end of stage 2 requires ≥9 of 30 treated pts meet this criterion. Key secondary endpoints include overall response rate, PFS, OS, safety/tolerability, PK and biomarkers of response. Results: In 33 treated SS pts with a median of 2 prior systemic treatments, best response of SD was observed in 11 pts (33%) with 5 pts (15%) having SD lasting ≥16 wks. No objective responses were observed. The protocol-defined success criterion at the end of study was not met. Tazemetostat was well-tolerated with grade 1/2 cough (36%), dyspnea (33%) and fatigue (33%) as the most frequently reported adverse events regardless of attribution. Conclusions: Tazemetostat was well tolerated with a favorable safety profile. Although there were no objective responses in heavily pretreated pts, the observation of SD in a subset of pts suggests further studies with tazemetostat in combination may be warranted in SS. Clinical trial information: NCT02601950.
Multiple balloon-like lesions in the small intestine of an adult with chronic diarrhoea
Authors: Cheng-Bei Zhou, Hong Lu, Ying-Xuan Chen, Jing-Yuan Fang
Journal: Gut (2018)

Clinical presentation A 28-year-old woman presented with a 3-year history of chronic watery diarrhoea along with abdominal pain and bloating, which could mostly be alleviated after defecation. Her symptom of diarrhoea, at least three times a day, could be relieved by neither probiotics nor antidiarrhoeal agents. She had also lost 5 kg in the last month. She denied family history, poor vaccine responses or significant infections in early childhood except for an allergy history to intravenous immunoglobulin (Ig) with immediate dyspnoea, palpitations and hypotension. Laboratory investigations suggested that the stool specimens were negative for viruses, parasites or bacteria. Laboratory evaluation revealed a low serum globulin level, 14.5 (reference range, 20–30 g/L); serum Ig levels were significantly abnormal: IgA &lt;0.27 (0.7–4 g/L), IgM 0.24 (0.4–2.3 g/L), IgG 1.3 (7–16 g/L); white cell count 15.4×10 9 /L (3.69–9.16×10 9 /L); C-reactive protein (CRP) 20.5 (normal &lt;10 mg/L); CD4+ lymphocyte/CD8+ lymphocyte 1.09% (1.5%–2%). Other laboratory findings were unremarkable, for example, tumour markers, autoantibodies and HIV, and so on. CT showed mesenteric nodule-like images and thickening of the wall and mucosa in small intestine. Peroral and transanal enteroscopy respectively demonstrated swelling mucosa and continuous granular lesions from duodenum to middle jejunum, and from middle ileum to terminal ileum (figure 1A–D). Figure 1 Endoscopic images show swelling mucosa, dense nodular lesions in duodenum (A), upper jejunum (B), upper ileum (C) and terminal ileum (D). Question What is the most likely diagnosis?
Phase II study of S-1 on alternate days combined with bevacizumab in elderly patients (aged ≥75 years) with metastatic colorectal cancer (mCRC).
Authors: Tetsuya Eto, Toshikazu Moriwaki, Hiroyasu Ishida, Shinji Endo, Yoshiyuki Yamamoto, Hidekazu Kuramochi, Mikio Sato, Akihito Tsuji, Yoshiaki Bando, Shunju Indou, Mitsuo Shimada, Kenji Amagai, Masamitsu Morimoto, Kazuma Kobayashi, Tomohiro Nishina, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2018)

750 Background: The alternate-days administration of S-1 was suggested to reduce toxicities such as GI-related adverse events (AEs) or neutropenia maintaining efficacy in some previous reports. This phase II study was aimed to evaluate an alternate-day administration of S-1 combined with bevacizumab in untreated elderly patients with mCRC. Methods: The key eligibility criteria included age ≥75 years, first-line chemotherapy, measurable lesions, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1, preserved organ function, and refusal of oxaliplatin- or irinotecan-containing regimen as the initial chemotherapy. Patients received 40 mg (body surface area [BSA] ≤1.25 m 2 ), 50 mg (BSA &gt; 1.25 to ≤1.50 m 2 ), or (BSA &gt; 1.50 m 2 ) of S-1 orally, twice a day, on Monday, Wednesday, Friday, and Sunday every week. Bevacizumab of 7.5 mg/kg was administered every 3 weeks. Primary endpoint was progression-free survival (PFS). Expected median PFS was 8.5 months, and efficacy threshold was 5.0 months. The required sample size was calculated as 50 patients, with a 2-sided type I error of 10% and a power of 80%. Results: Of 54 enrolled patients, 50 patients for efficacy and 53 patients for safety were evaluated. The median age was 79 years (range, 75–88), and 56% had an ECOG PS of 0. The median follow-up time was 34.5 months (95% confidence interval [CI], 25.6–44.9). Median PFS was 8.1 months (95%CI, 7.4–10.1). Median overall survival was 22.8 months (95%CI, 16.9–28.5). The response rate and disease control rate were 44% and 88%, respectively. Grade 3 or more hematologic, non-hematologic, and bevacizumab-related AEs were observed in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Treatment-related death caused by cerebral infarction was observed in one patient. Conclusions: The primary endpoint was met. The alternate-days administration of S-1 combined with bevacizumab was well tolerated and effective in elderly patients with mCRC. Clinical trial information: UMIN000010402.
All for One and One for All: Mental Disorders in One Dimension
Authors: Avshalom Caspi, Terrie E. Moffitt
Journal: American Journal of Psychiatry (2018)

In both child and adult psychiatry, empirical evidence has now accrued to suggest that a single dimension is able to measure a person’s liability to mental disorder, comorbidity among disorders, persistence of disorders over time, and severity of symptoms. This single dimension of general psychopathology has been termed “p,” because it conceptually parallels a dimension already familiar to behavioral scientists and clinicians: the “g” factor of general intelligence. As the g dimension reflects low to high mental ability, the p dimension represents low to high psychopathology severity, with thought disorder at the extreme. The dimension of p unites all disorders. It influences present/absent status on hundreds of psychiatric symptoms, which modern nosological systems typically aggregate into dozens of distinct diagnoses, which in turn aggregate into three overarching domains, namely, the externalizing, internalizing, and psychotic experience domains, which finally aggregate into one dimension of psychopathology from low to high: p. Studies show that the higher a person scores on p, the worse that person fares on measures of family history of psychiatric illness, brain function, childhood developmental history, and adult life impairment. A dimension of p may help account for ubiquitous nonspecificity in psychiatry: multiple disorders share the same risk factors and biomarkers and often respond to the same therapies. Here, the authors summarize the history of the unidimensional idea, review modern research into p, demystify statistical models, articulate some implications of p for prevention and clinical practice, and outline a transdiagnostic research agenda. [AJP AT 175: Remembering Our Past As We Envision Our Future October 1910: A Study of Association in Insanity Grace Helen Kent and A.J. Rosanoff:
Choroidal and Sub-Retinal Pigment Epithelium Caverns
Authors: Rosa Dolz-Marco, Jay P. Glover, Orly Gal-Or, Katie M. Litts, Jeffrey D. Messinger, Yuhua Zhang, Mariano Cozzi, Marco Pellegrini, K. Bailey Freund, Giovanni Staurenghi, Christine A. Curcio
Journal: Ophthalmology (2018)
Specificity of methylated <i>BCAT1</i> and <i>IKZF1</i> for colorectal cancer.
Authors: Erin L. Symonds, Beibei Yao, Susanne Kartin Pedersen, David Murray, Graeme P Young
Journal: Journal of Clinical Oncology (2018)

580 Background: Methylated BCAT1 and IKZF1 are useful circulating tumor DNA (ctDNA) biomarkers for detection and following the course of colorectal cancer (CRC). This study aimed to determine the specificity of methylated BCAT1/ IKZF1 for CRC detection by assaying specimens from patients with other adenocarcinomas. Methods: Blood was collected from patients with invasive adenocarcinoma of the prostate (n = 32), breast (16), oesophagus (15) or colon/rectum (212), prior to any treatment or resection, and from 245 clinically assessed controls with no known prior or current adenocarcinoma. Biopsies were collected from cancer tissue and adjacent non-neoplastic tissue either prior to treatment or at surgery from 9 prostate, 26 breast, 6 oesophagus, 15 CRC cases. All specimens were assayed for methylated BCAT1 and IKZF1 DNA. Calculation of positivity rates: tissue, the proportion of tissue cases with ≥ 5% methylation; blood, the proportion of cases with any detectable signal of either marker. Results: ctDNA positivity rates were significantly higher in CRC (126/212, 59.4%, 95% CI: 52.5 - 66.1) and oesophageal cancer (6/16, 33.3%, 11.0 - 58.7) cases only compared to controls (16/245, 6.5%, 3.8 - 10.4; p &lt; 0.01). ctDNA was more likely to be positive in late stage cancers, although only significant for CRC, Table. Cancer tissue positivity rates were: CRC, 15/15, 100% (96.4 - 100); oesophageal, 5/6, 83.3% (35.9 - 99.6); prostate, 4/9, 44.4% (13.7 - 78.8); breast, 5/26, 19.2% (6.6 - 39.4). All cancer tissues had significantly higher methylation levels than the adjacent tissue (Chi 2 test, p &gt;0.05). Conclusions: Only colorectal and oesophageal cancer patients had significantly higher ctDNA positivity rates (using methylated BCAT1/IKZF1) compared to controls. This was also reflected in a higher proportion of cases showing methylation in the cancer tissue. The methylated BCAT1/IKZF1 blood test should be investigated further as a screening and surveillance tool for oesophageal cancer. [Table: see text]
Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers
Authors: Nikita Pozdeyev, Laurie M. Gay, Ethan S. Sokol, Ryan Hartmaier, Kelsi E. Deaver, Stephanie Davis, Jena D. French, Pierre Vanden Borre, Daniel V. LaBarbera, Aik-Choon Tan, Rebecca E. Schweppe, Lauren Fishbein, Jeffrey S. Ross, Bryan R. Haugen, Daniel W. Bowles
Journal: Clinical Cancer Research (2018)

Abstract Purpose: To define the genetic landscape of advanced differentiated and anaplastic thyroid cancer (ATC) and identify genetic alterations of potential diagnostic, prognostic, and therapeutic significance. Experimental Design: The genetic profiles of 583 advanced differentiated and 196 ATCs generated with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT and FoundationOne were analyzed. Results: ATC had more genetic alterations per tumor, and pediatric papillary thyroid cancer had fewer genetic alterations per tumor when compared with other thyroid cancer types. DNA mismatch repair deficit and activity of APOBEC cytidine deaminases were identified as mechanisms associated with high mutational burden in a subset of differentiated thyroid cancers and ATCs. Copy number losses and mutations of CDKN2A and CDKN2B, amplification of CCNE1, amplification of receptor tyrosine kinase genes KDR, KIT, and PDGFRA, amplification of immune evasion genes CD274, PDCD1LG2, and JAK2, and activating point mutations in small GTPase RAC1 were associated with ATC. An association of KDR, KIT, and PDGFRA amplification with the sensitivity of thyroid cancer cells to lenvatinib was shown in vitro. Three genetically distinct types of ATCs are proposed. Conclusions: This large-scale analysis describes genetic alterations in a cohort of thyroid cancers enriched in advanced cases. Many novel genetic events previously not seen in thyroid cancer were found. Genetic alterations associated with anaplastic transformation were identified. An updated schematic of thyroid cancer genetic evolution is proposed. Clin Cancer Res; 24(13); 3059–68. ©2018 AACR.
Abstract 18539: Circulating microRNAs and Inflammatory Markers Associated With Heart Failure Development Post-Myocardial Infarction
Authors: Ana Holley, Kirsty Danielson, Gisela Kristono, Scott Harding, Peter Larsen
Journal: Circulation (2017)

Background: The development of heart failure (HF) following an acute myocardial infarction (AMI) remains a significant clinical problem. However the early prediction of left ventricular (LV) remode...
The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer
Authors: Tuo Li, Zhijian J. Chen
Journal: The Journal of Experimental Medicine (2018)

Detection of microbial DNA is an evolutionarily conserved mechanism that alerts the host immune system to mount a defense response to microbial infections. However, this detection mechanism also poses a challenge to the host as to how to distinguish foreign DNA from abundant self-DNA. Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is a DNA sensor that triggers innate immune responses through production of the second messenger cyclic GMP-AMP (cGAMP), which binds and activates the adaptor protein STING. However, cGAS can be activated by double-stranded DNA irrespective of the sequence, including self-DNA. Although how cGAS is normally kept inactive in cells is still not well understood, recent research has provided strong evidence that genomic DNA damage leads to cGAS activation to stimulate inflammatory responses. This review summarizes recent findings on how genomic instability and DNA damage trigger cGAS activation and how cGAS serves as a link from DNA damage to inflammation, cellular senescence, and cancer.
Further Questions Regarding Electrocardiogram Prior to Liver Transplant
Authors: Nicolas Bakinde, Taiwo A. Ajose, Eric Y. Chang
Journal: JAMA Internal Medicine (2018)

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Practical Guide to Surgical Data Sets: Society for Vascular Surgery Vascular Quality Initiative (SVS VQI)
Authors: Sapan S. Desai, Amy H. Kaji, Gilbert Upchurch
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Targeting mitochondrial pyruvate carrier in nonalcoholic steatohepatitis: Growing evidence and future challenges
Authors: Giovanni Musso, Roberto Gambino
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the article by McCommis et al. reporting on the antifibrotic properties of the mitochondrial pyruvate carrier (MPC) inhibitor MSDC‐0602 in a mouse model of nonalcoholic steatohepatitis (NASH).1 MSDC‐0602 belongs to a class of next‐generation thiazolidinedione insulin sensitizers that potently bind and inhibit the MPC protein but have negligible peroxisome proliferator–activated receptor‐gamma (PPAR‐γ) binding activity, the latter being responsible for the undesired thiazolidinedione‐related effects of weight gain, edema, and bone fractures. Growing human evidence indirectly supports the effectiveness of this approach in NASH: when we compared the effect between pioglitazone and rosiglitazone on liver histology in patients with NASH, we found that pioglitazone, which possesses both PPAR‐γ agonist activity and MPC inhibiting activity, reversed NASH and advanced fibrosis in nondiabetic patients, while rosiglitazone, a more potent PPAR‐γ agonist devoid of MPC‐binding activity, did not.2 Furthermore, in nondiabetic insulin‐resistant patients with prior acute cerebrovascular disease enrolled in the Insulin Resistance Intervention after Stroke (IRIS) trial, pioglitazone reduced the risk of new‐onset diabetes and new cardiovascular events.3 Although the presence of nonalcoholic fatty liver disease was not reported in this trial, the benefits were largely driven by the effect of pioglitazone in patients with metabolic syndrome, which is commonly encountered in nonalcoholic fatty liver disease. Although collectively encouraging, some questions remain: compared with PPAR‐γ agonists, MPC modulators are weaker stimulators of the secretion of adiponectin, a key anti‐inflammatory antifibrotic adipokine.1 Although in strictly controlled experimental conditions the weight loss associated with adipocyte browning may partially make up for the lack of PPAR‐γ‐stimulated adiponectin secretion, the difficulty in maintaining a durable weight loss in real life may blunt the benefits of this approach. Furthermore, recent metabolomics analysis identified compensatory changes in hepatic amino acid and lipid metabolism that may offset long‐term effects of MPC inhibition.5 These factors need to be taken into account in the design and monitoring of the effects of MPC modulators in human trials.