tbuckley/cabot-search huggingface dataset:
High-Coverage Targeted Lipidomics Reveals Novel Serum Lipid Predictors and Lipid Pathway Dysregulation Antecedent to Type 2 Diabetes Onset in Normoglycemic Chinese Adults
Authors: Jieli Lu, Sin Man Lam, Qin Wan, Lixin Shi, Yanan Huo, Lulu Chen, Xulei Tang, Bowen Li, Xueyan Wu, Kui Peng, Mian Li, Shuangyuan Wang, Yu Xu, Min Xu, Yufang Bi, Guang Ning, Guanghou Shui, Weiqing Wang
Journal: Diabetes Care (2019)

OBJECTIVE Comprehensive assessment of serum lipidomic aberrations before type 2 diabetes mellitus (T2DM) onset has remained lacking in Han Chinese. We evaluated changes in lipid coregulation antecedent to T2DM and identified novel lipid predictors for T2DM in individuals with normal glucose regulation (NGR). RESEARCH DESIGN AND METHODS In the discovery study, we tested 667 baseline serum lipids in subjects with incident diabetes and propensity score–matched control subjects (n = 200) from a prospective cohort comprising 3,821 Chinese adults with NGR. In the validation study, we tested 250 lipids in subjects with incident diabetes and matched control subjects (n = 724) from a pooled validation cohort of 14,651 individuals with NGR covering five geographical regions across China. Differential correlation network analyses revealed perturbed lipid coregulation antecedent to diabetes. The predictive value of a serum lipid panel independent of serum triglycerides and 2-h postload glucose was also evaluated. RESULTS At the level of false-discovery rate &amp;lt;0.05, 38 lipids, including triacylglycerols (TAGs), lyso-phosphatidylinositols, phosphatidylcholines, polyunsaturated fatty acid (PUFA)–plasmalogen phosphatidylethanolamines (PUFA-PEps), and cholesteryl esters, were significantly associated with T2DM risk in the discovery and validation cohorts. A preliminary study found most of the lipid predictors were also significantly associated with the risk of prediabetes. Differential correlation network analysis revealed that perturbations in intraclass (i.e., non–PUFA-TAG and PUFA-TAGs) and interclass (i.e., TAGs and PUFA-PEps) lipid coregulation preexisted before diabetes onset. Our lipid panel further improved prediction of incident diabetes over conventional clinical indices. CONCLUSIONS These findings revealed novel changes in lipid coregulation existing before diabetes onset and expanded the current panel of serum lipid predictors for T2DM in normoglycemic Chinese individuals.
Essential building blocks for colonoscopy quality improvement initiatives: a dedicated database, automation, and appropriate financial incentives
Authors: Subhas Banerjee
Journal: Endoscopy (2019)

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality in the western world. Colonoscopy has assumed a predominant role in CRC screening, because of its high sensitivity, the ability to perform concurrent polypectomy, and its advantage, over other screening strategies, of allowing longer intervals between testing. Although colonoscopy is associated with a reduction in CRC mortality [1], interval cancers, which account for 3 % – 9 % of all colon cancers, remain a persistent and troubling issue. Although some interval cancers may represent de novo accelerated biology-related cancers, it is believed that the majority are attributable to missed, or to incompletely resected lesions. High quality colonoscopy is therefore a fundamental prerequisite for reduction in CRC mortality. Consequently, quality indicators/performance measures for colonoscopy have been developed by gastrointestinal societies in the United States [2], and more recently by the European Society of Gastrointestinal Endoscopy (ESGE) [3], with the goal of quantifying the quality of colonoscopy. Substantial variability has been demonstrated in the quality of colonoscopy between endoscopists, resulting in suboptimal CRC prevention [4]. This has provided impetus for the implementation of quality assurance programs, typically comprising continuous quality assessment, with intermittent feedback and quality improvement interventions. In this issue of Endoscopy, Bugajski and colleagues evaluate the performance of the Polish Colonoscopy Screening Program (PCSP) in adhering to the ESGE quality guidelines over the years 2014 – 2015, capturing the performance of 25 endoscopy units and 117 endoscopists over a total of 43 277 screening colonoscopies.
Automated Manufacture of CAR19 Donor Lymphocytes Incorporated into an Escalated Dose DLI Protocol: Preliminary Results from the CARD Study
Authors: Claire Roddie, Lauren Nickolay, Ulrike Mock, Praveen Aujla, Gordon W Cheung, Lucas Chan, Alex Day, Graham Wheeler, Bilyana Popova, Kim Champion, Yashma Pathak, Nasir Mahmoud, Helen Lowe, Gulrukh Ahsan, Nourredine Himoudi, Farzin Farzaneh, David C. Linch, Adrian J Thrasher, Martin Pule, Waseem Qasim, Karl Peggs
Journal: Blood (2017)
Clinicians and Cognitive Bias: A Case of Frontotemporal Dementia Misdiagnosed as Conversion Disorder
Authors: Benjamin R. Braus, Teresa A. Rummans, Maria I. Lapid, Robert J. Morgan, Shirlene M. Sampson, Elliot M. Handler, Joel E. Dimsdale
Journal: American Journal of Psychiatry (2019)

Every specialty of medicine is concerned with misdiagnosis.Recent developments in behavioral economics offer a helpful perspective on nonrational influences or cognitive biases that intrude on important decision making.The case presented here highlights how cognitive bias can affect both diagnosis and treatment of patients."Ms.A," a 47-year-old woman with a 2.5-year history of worsening symptoms of depression, anxiety, impaired speech, bradykinesia, and incoordination, was referred to a tertiary medical center for further evaluation and treatment of conversion disorder complicated by depression and anxiety.Symptom onset followed the suicide of her college-age son, and her symptoms eventually rendered her nearly mute and unable to perform activities of daily living.Previous psychiatric and neurological evaluations had been conducted approximately 6 months before her referral and were inconclusive.Neuropsychological testing revealed abnormalities in memory and speech.These findings were interpreted as effort dependent and labeled as possible conversion disorder (also known as functional neurological disorder).CSF studies were reported to be normal.A brain MRI report described possible cerebral atrophy.The patient's medical history included asthma and hyperlipidemia.Her only prior psychiatric history was mild depression approximately 8 years earlier, for which she was treated with several selective serotonin reuptake inhibitors.Ms.A had been raised by her adoptive mother and her biological father, and there was no history of abuse or trauma.After completing an associate's degree, she was employed until the presenting illness rendered her disabled.She was married and had two children.Family history of psychiatric illness included suicides in her son and a grandfather.Ms. A was admitted to the psychiatric hospital for diagnostic clarification and treatment.The working diagnosis on admission was severe major depression with catatonia, although concern was also noted for an underlying neurological illness, and her prior diagnosis of conversion disorder was retained.Trials of benzodiazepines, various antidepressants and antipsychotics, and an acute course of ECT were ineffective.A neurological
Somatic Mutations of Myeloid Malignancy-Associated Genes in Acquired Pure Red Cell Aplasia in Adults
Authors: Makoto Hirokawa, Junki Kohmaru, Souichi Koyota, Keiji Kuba, Naohito Fujishima, Tomoo Saga, Ayumi Omokawa, Shigeharu Ueki, Fumihiro Ishida, Shinji Nakao, Akira Matsuda, Akiko Ohta, Kaoru Tohyama, Ryuji Suzuki, Kinuko Mitani
Journal: Blood (2018)
Identification of stage I/II colorectal cancer patients at risk of recurrence: The role of elastica stains to detect venous invasion.
Authors: Campbell SD Roxburgh, Alan K Foulis, Manal Atwan, Paul G Horgan, Donald C. Mcmillan
Journal: Journal of Clinical Oncology (2012)

e14117 Background: Venous invasion (VI) is a high-risk characteristic in colorectal cancer (CRC) and in stage II disease guides provision of adjuvant therapy. However, reported rates vary in published studies from 10-90%. We recently reported use of elastica stains improve reproducibility of reporting, increasing rates to &gt;50% (Roxburgh, Ann Surg, 2010). Furthermore, compared to H&amp;E alone, elastica detected VI provided superior prediction of 3yr cancer survival in an unselected cohort of CRC patients. The present study aims to examine how the approach could be used in patients with node negative CRC. Methods: We retrieved pre-2003 tumour blocks, sectioned and stained them with elastica. Post-2003, elastica detected VI was routinely reported. A minimum of 3 blocks was required for analysis. Those who died within 30 days of surgery or had neoadjuvant therapy were excluded. Results: 244 stage I/II patients underwent surgery between 1997-2006. 65 cases pre-2003 were analyzed retrospectively. The rate of elastica detected VI was 54%. Elastica detected VI related to other high-risk pathology including T stage (p&lt;0.001), serosal invasion (p&lt;0.01), tumour grade (p&lt;0.05) and low-grade lymphocytic infiltrate (P&lt;0.05). Minimum follow-up was 5 yrs; mean follow-up 99 months (60-178), during which there were 99 deaths, 48 from cancer. Absence of VI related to improved 5-yr cancer specific survival (93% vs 66%). On multivariate analysis, VI independently related to cancer specific survival (HR=5.5,95%CI 2-13,p&lt;0.001) with margin involvement (HR=2.4,95%CI 1-6,p=0.067) and serosal involvement (HR=2.2,95%CI1-4, p=0.015). For CRC mortality, the area under the receiver operator curve was highest for VI compared with other pathology (AUC 0.69, 95%CI 0.6-0.8, P&lt;0.001). Absence of VI related to 5-yr survivals of 92% and 97% in colon and rectal cancer respectively. Conclusions: More objective assessment of VI with routine elastica staining provides accurate prediction of survival in stage I/II CRC. Presence of VI was associated with a 5.5 fold increased risk of cancer death at 5 yrs. Such results support routine use of elastica stains to identify patients with node negative disease at risk of recurrence.
Limited sustained response after stopping nucleos(t)ide analogues in patients with chronic hepatitis B: results from a randomised controlled trial (Toronto STOP study)
Authors: Kin Seng Liem, Scott Fung, David K Wong, Colina Yim, Seham Noureldin, Jiayun Chen, Jordan J Feld, Bettina E Hansen, Harry L A Janssen
Journal: Gut (2019)

Although most patients with chronic hepatitis B (CHB) reach effective virological suppression with long-term nucleos(t)ide analogues (NA) therapy, some might not need to continue treatment for life. In this randomised, controlled, phase IV trial, we evaluated off-therapy outcomes in patients after discontinuing long-term NA therapy.Patients who had received NA therapy for ≥1 year and achieved virological suppression (hepatitis B e antigen (HBeAg) seroconversion combined with undetectable hepatitis B virus (HBV) DNA ≥12 months in HBeAg-positive patients or undetectable HBV DNA ≥36 months in HBeAg-negative patients) were randomised 2:1 to stop or continue NA therapy for 72 weeks. Sustained disease remission (HBeAg negative, HBV DNA <2000 IU/mL and normal alanine aminotransferase (ALT)) was evaluated at 72 weeks after stopping NA therapy.Among 67 enrolled patients, sustained disease remission was observed in 13/45 (29%) stop versus 18/22 (82%) continue patients. Hepatitis B surface antigen (HBsAg) loss occurred in two patients (one in each group). The median HBsAg decline from randomisation to week 72 was similar in both groups (0.2 (0.0-0.4) vs 0.1 (0.0-0.2) log IU/mL in stop vs continue patients). Among patients who stopped, 15/45 (33%) had virological or biochemical relapse and 17/45 (38%) were retreated according to predefined criteria. A total of 11/18 (61%) pretreatment HBeAg-positive versus 6/27 (22%) HBeAg-negative patients required retreatment (p=0.01). Fourteen (31%) patients developed ALT >10× upper limit of normal (ULN) and another 7 (16%) had ALT >5× ULN. No patients experienced liver decompensation or died.The findings of this prospective study suggest limited benefit of stopping NA therapy in chronic hepatitis B.NCT01911156.
Cost-effectiveness of Low-density Lipoprotein Cholesterol Level–Guided Statin Treatment in Patients With Borderline Cardiovascular Risk
Authors: Ciaran N. Kohli-Lynch, Brandon K. Bellows, George Thanassoulis, Yiyi Zhang, Mark J. Pletcher, Eric Vittinghoff, Michael J. Pencina, Dhruv Kazi, Allan D. Sniderman, Andrew E. Moran
Journal: JAMA Cardiology (2019)

American College of Cardiology/American Heart Association cholesterol guidelines prioritize primary prevention statin therapy based on 10-year absolute risk (AR10) of atherosclerotic cardiovascular disease (ASCVD). However, given the same AR10, patients with higher levels of low-density lipoprotein cholesterol (LDL-C) experience greater absolute risk reduction from statin therapy.
Bidirectional linkage between the B-cell receptor and NOTCH1 in chronic lymphocytic leukemia and in Richter’s syndrome: therapeutic implications
Authors: Francesca Arruga, Valeria Bracciamà, Nicoletta Vitale, Tiziana Vaisitti, Katiuscia Gizzi, Alison Yeomans, Marta Coscia, Giovanni D’Arena, Gianluca Gaidano, John N. Allan, Richard R. Furman, Graham Packham, Francesco Forconi, Silvia Deaglio
Journal: Leukemia (2019)
Efficacy and safety of amrubicin in patients with advanced or recurrent thymoma.
Authors: Kiyotaka Yoh, Koichi Goto, Seiji Niho, Shigeki Umemura, Hironobu Ohmatsu, Yuichiro Ohe
Journal: Journal of Clinical Oncology (2012)

e17513 Background: Thymoma is rare thoracic tumor, which is chemoresponsive with anthracycline or cisplatin-containing regimen in advanced or recurrent setting. Amrubicin is a novel anthracycline agent that is well known to exert significant activity against small-cell lung cancer. The purpose of this study was to determine the efficacy and safety of amrubicin in patients with advanced or recurrent thymoma. Methods: We reviewed 11 consecutive patients with advanced or recurrent thymoma treated with single-agent amrubicin therapy at our institution from May 2006 to September 2010, retrospectively. Amrubicin was administered intravenously at 40 or 45 mg/m 2 on day 1 to 3 of 3-4 weeks until disease progression or development of intolerance. Results: Profile of patients included: median age was 57 years (range 25–74); Male/Female=5/6; PS 0/1= 7/4; and Masaoka stage IVA/IVB/recurrence=7/2/2. All patients had received no prior chemotherapy. The median number of treatment cycles was 4 (range 3-6). A partial response was achieved in 1 patient and 10 patients exhibited stable disease. The overall response rate was 9%, but 3 patients had at least a 20% reduction in tumor size with amrubicin. The median reduction rate in tumor size was 13% (range 0-40). The median progression-free survival period was 5.4 months (range 2.3-15.8 months). The median overall survival has not been reached although a median follow-up time was 2.5 years. Based on the Kaplan-Meier method, the estimated 3-year survival rate was 83%. The most common adverse events were hematological toxicities. Five patients had grade 3/4 neutropenia, but febrile neutropenia was not observed. Non-hematological grade 3 toxicities were less frequent. There were no treatment-related deaths. Conclusions: Single-agent amrubicin showed modest activity and acceptable safety profile as chemotherapy for advanced or recurrent thymoma. Additional testing of amrubicin combined with cisplatin in this disease is warranted.
Effect of chemotherapy and psychosocial distress parameters on perceived cognitive disturbances in Asian breast cancer patients.
Authors: Yin Ting Cheung, Maung Shwe Ham Guo, Wai Keung Chui, Rebecca Alexandra Dent, Yoon Sim Yap, Soo Kien Lo, Raymond C.H. Ng, Alexandre Chan
Journal: Journal of Clinical Oncology (2012)

9041 Background: A qualitative study has revealed that Asian breast cancer patients attributed their post-chemotherapy cognitive disturbances to psychosocial distress. To validate this claim, we aim to examine perceived cognitive disturbances, anxiety and quality of life (QoL) in Asian breast cancer patients and to identify clinical and psychosocial factors associated with perceived cognitive disturbances. Methods: A prospective, observational study was held at the largest cancer center in Singapore. Chemotherapy (CT) and non-chemotherapy (non-CT) receiving breast cancer patients completed self- reported questionnaires to assess the following domains: patients’ perceived impact of chemotherapy on cognitive disturbances (FACT-Cog), health-related QoL (EORTC QLQ-C30) and anxiety (Beck Anxiety Inventory). Multiple regression was conducted to delineate factors associated with perceived cognitive impairment. Results: A total of 166 (1:1 CT/non-CT) patients were recruited (age: 54.1±10.2 years; 78.9% Chinese; 53.6% post-menopausal). Most of the CT patients received anthracycline-based chemotherapy (93.1%) and anti-hormonal therapy (69.4%). Comparing to non-CT patients, CT patients experienced more fatigue (QLQ-C30 fatigue scores: 22.2 vs 33.3 points; p=0.005), more significant anxiety (8.6% vs 21.9%; p=0.002), and more cognitive disturbances (FACT-Cog scores: 110 vs 124 points; p&lt;0.0001). Regression model identified chemotherapy, anti-hormonal therapy, emotional functioning and global health status to be strongly associated with cognitive disturbances in Asian breast cancer patients. The interacting effect between anxiety and fatigue, comparing to fatigue alone, was more associated with cognitive disturbances (β=-0.212; p=0.032 vs β=-0.07; p=0.25, respectively). Conclusions: This is the first study to demonstrate that Asian breast cancer patients experiencing both fatigue and anxiety are more predisposed to cognitive disturbances. Post-chemotherapy cognitive changes are observed in our patients, and our results suggest that psychosocial factors are impactful to identify cancer patients who are more susceptible to cognitive disturbances.
Functional Nervous Disorders: Their Classification and Treatment.
Journal: JAMA (1923)

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Epigenetic Silencing of Arginino-Succinate Synthase (ASS1) Defines Arginine Depletion Therapy as a Novel Treatment Strategy for Breast Cancer
Authors: F. Cavicchioli, A. Shia, K. O'Leary, V. Haley, C. Palmieri, N. Syed, T. Crook, A.M. Thompson, C. Lo Nigro, P. Schmid
Journal: Annals of Oncology (2012)
Palliative Prognostic Index application at an inpatient palliative care service from a Brazilian tertiary Hospital: A prospective observational study.
Authors: Tiago Pugliese Branco, Alze Pereira dos Santos Tavares, Mariana Sarkis Braz, Mariana Ribeiro Monteiro, Ana Beatriz Kinupe Abrahao, Thiago A. F. de Menezes, Carolina Paparelli, Carolina Sassaki Kishimoto, Helena M. F. Medeiros, Karen Ebina, Luciana R. B. Cabral, Maria Clara Fernandes, Silvia Cortizo, Fabiola Borges, Simone Nagashima, Pedro Nazareth Aguiar
Journal: Journal of Clinical Oncology (2019)

11537 Background: Palliative Care Index (PPI) has been proposed to improve the accuracy of survival prediction for advanced cancer patients. The aim of this study is to investigate the feasibility and real-world prognosis survival of oncology inpatients from a Brazilian tertiary hospital using PPI. Methods: Hospitalized advanced cancer patients who have been referred to the Palliative Care Team were enrolled from May 2011 to December 2018. The PPI was collected within 24 hours of the referral by the palliative care physician. Primary endpoint was median overall survival (OS), estimated with the use of the Kaplan–Meier method, in three groups: PPI &lt; 4.0; 4.0 ≤ PPI &gt; 6.0 and PPI ≥ 6.0. Secondary endpoints were OS rate at 3-week for patients with PPI ≥ 6.0, and the most accurate PPI value to predict 6 and 3-week survival, calculated by ROC curve. Results: Total of 1.381 patients were included in this cohort with a median age of 68-year-old, and 51.3% of females. The most frequent primary cancer sites were lung/chest (17,2%), colorectal (14,3%), breast (11,2%), and biliopancreatic (10,9%). Among 454 patients with PPI &lt; 4.0, median OS was 44 days (95% CI: 35,5-52,4); 20 days (95% CI: 15,4-24,5) for 260 patients with 4.0≤ PPI &lt; 6.0 and 8 days (95% CI: 7-8,9) between 655 patients with PPI ≥ 6. Differences in OS among the groups adjusted for primary site, age and gender were significant (p &lt; 0,001). OS rate at 3 weeks for PPI≥ 6.0 was 28.1% (OR 5,39 p &lt; 0.001). PPI value of &lt; 5,5 best predicted 6-week OS (79% sensibility, 55% specificity, AUC 0,714) and the PPI value of ≥ 5,5 predicted 3-week OS (67% sensibility, 73% specificity, AUC 0,753). Conclusions: PPI is feasible and suitable for routine clinical practice to predict survival among Brazilian patients with advanced cancer. In our study, PPI 5.5 seems to be the most accurate value to predict survival within 3 weeks.
Suicide following presentation to hospital for non-fatal self-harm in the Multicentre Study of Self-harm: a long-term follow-up study
Authors: Galit Geulayov, Deborah Casey, Liz Bale, Fiona Brand, Caroline Clements, Bushra Farooq, Nav Kapur, Jennifer Ness, Keith Waters, Apostolos Tsiachristas, Keith Hawton
Journal: The Lancet Psychiatry (2019)
Clare Gerada: Preventing suicide in medical staff
Authors: Clare Gerada
Journal: BMJ (2019)

I recently experienced a first in my career: while presenting at a conference, I shed tears.

To put things in context, I was talking at a session on preventing suicide in the NHS. Before mine, we heard brilliant talks from two paramedics, an ambulance controller, and a nurse, talking from their respective fields. As they gave their presentations I found myself reflecting on the group I had run that week—one I’ve written about before in BMJ Opinion.1 It’s a group no one wants to belong to, but it’s one that’s vital for the survival of its members. This is …