tbuckley/cabot-search huggingface dataset:
Time to Add a Fifth Pillar to Bedside Physical Examination
Authors: Jagat Narula, Y. Chandrashekhar, Eugene Braunwald
Journal: JAMA Cardiology (2018)

Inspection, palpation, percussion, and auscultation have been the 4 pillars of clinical bedside medicine. Although these basic methods of physical examination have served us well, traditional bedside examination, for a number of reasons including diminishing interest and expertise, performs well less than what is required of a modern diagnostic strategy. Improving the performance of physical examination is vital given that it is crucial to guide diagnostic possibilities and further testing. Current efforts at improving physical examination skills during medical training have not been very successful, and incorporating appropriate technology at the bedside might improve its performance. Selective use of bedside ultrasound (or insonation) can be one such strategy that could be incorporated as the fifth component of the physical examination. Seeing pathology through imaging might improve interest in physical examination among trainees, and permit appropriate downstream testing and possibly superior decision making. Current ultrasound technology makes this feasible, and further miniaturization of ultrasound devices and reduced cost will allow for routine use at the bedside. It is time to have a wider debate and a possible consensus about updates required to enhance current paradigms of physical examination.
Magic mirror on the wall: Which is the best biomarker for hepatocellular carcinoma?
Authors: Teh‐Ia Huo, Chia‐Yang Hsu, Po‐Hong Liu
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. Supported by Taipei Veterans General Hospital, Taiwan (V106C‐021, VN106‐11). TO THE EDITOR: We read with interest the paper, "A large‐scale, multicenter serum metabolite biomarker identification study for the early detection of hepatocellular carcinoma," by Luo et al. published in an upcoming issue of Hepatology.1 A few concerns which could compromise the paper's conclusions may deserve the authors' attention. Serum α‐fetoprotein (AFP) is widely used for hepatocellular carcinoma (HCC) detection and screening. In this study, however, it is quite striking that the area under receiver‐operating characteristic curve (AUC) for AFP was only 0.657 in the discovery set because the reported AUC in most published studies was between 0.72 and 0.89, depending on tumor characteristics.2 Notably, several novel biomarkers, such as des‐gamma carboxyprothrombin, lens culinaris agglutinin‐reactive AFP, insulin‐like growth factor‐2, Golgi protein‐73 and human hepatocyte growth factor, have all been raised as potential tumor markers for HCC, but none has been validated for clinical use. An important feature of a classical tumor marker is that its blood levels should correlate with tumor burden. It is well known that serum AFP levels tend to increase with larger tumors. Therefore, it would be interesting to know if there is a correlation between the metabolite biomarker (phenylalanyl‐tryptophan and glycocholate) and the size of tumor. In addition, a significant drop of serum metabolite levels after tumor eradication is also indirect evidence that the marker is truly released from the tumors. There is another methodological question regarding this study. To confirm if the metabolite biomarker could predict the development of HCC, the best way is to perform Kaplan‐Meier analysis during the follow‐up period rather than testing multiple AUCs at different specific time points. Moreover, since most patients in the authors' series had chronic hepatitis B, baseline viral load and the presence of cirrhosis are also known crucial factors to determine cancer development. Collectively, the proposed metabolite biomarker still has many challenges to overcome to be judged as a genuine biomarker for HCC.
CAN WE TRUST AORTIC VALVE AREA FUSION AS GOLD STANDARD METHOD IN SYMPTOMATIC PATIENTS WITH SEVERE AORTIC STENOSIS?
Authors: Eirini Dri, Manolis Vavuranakis, Maria Kariori, Gerasimos Siasos, Konstantinos Kalogeras, Charalampos Kalantzis, Carmen-Maria Moldovan, Evangelia Bei, Angel Michail Kolokathis, Evangelos Oikonomou, Dimitrios Tousoulis
Journal: Journal of the American College of Cardiology (2018)
<i>JAMA Surgery</i>—The Year in Review, 2017
Authors: Melina R. Kibbe
Journal: JAMA Surgery (2018)

was an exciting year for JAMA Surgery, as the journal experienced several notable accomplishments.First, as evidence of the high-quality scientific publications in JAMA Surgery, the impact factor rose significantly from 5.7 to 7.96.This incredible accomplishment reflects the hard work of our authors, peer reviewers, 1 and editorial team.The impact factor of 7.96 positions JAMA Surgery as the second highest ranked of 197 surgery journals.Another measure of article impact is the Altmetric score, which quantifies the quality and amount of electronic attention an article receives from news and social media around the world.Our top 3 articles 2-4 for Altmetric score from the past year are listed in the Table .In another indication of success, in 2017, JAMA Surgery had a 28% increase in submissions to the journal, going from 1482 in 2016 to 1898 in 2017 (Table ).Even with this significant increase in submissions, the acceptance rate for all article types was 20%; for original investigations, 9%; and for research letters, 23%.The web and social media presence for JAMA Surgery continues to be very strong under the leadership of Amalia Cochran, MD, our web and social media editor.Our electronic tables of contents are delivered to 57 000 individuals.We currently have 20 900 Twitter followers, which represents a 34% increase in 2017.We currently have 22 263 Facebook followers, which represents a 50% increase in 2017.Thus, between the electronic tables of contents, visits to our website, social media reach, and our print distribution, JAMA Surgery reaches more than 60 000 individuals weekly.In addition, JAMA Surgery continues to publish 6 podcasts per year.These podcasts are now being conducted by Dr Cochran, who brings a new level of insight into the interview process with authors.
ELIGIBILITY VARIES ACROSS THE 3 SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITOR CARDIOVASCULAR OUTCOMES TRIALS AMONG ADULTS WITH TYPE 2 DIABETES: IMPLICATIONS FROM ANALYSIS OF THE DIABETES COLLABORATIVE REGISTRY
Authors: Eric Wittbrodt, David Chamberlain, Suzanne Arnold, Fengming Tang, Mikhail Kosiborod
Journal: Journal of the American College of Cardiology (2018)
Points to keep in mind when carrying out clinical trials in Japan on advanced pancreatic cancer cases without alternative treatments: Analysis of 367 cases.
Authors: Giichiro Tsurita, Hiroshi Yasui, Tomohiro Kurokawa, Yuichiro Yoshioka, Kentaro Yazawa
Journal: Journal of Clinical Oncology (2018)

243 Background: We commenced a physician-led clinical trial to examine the efficacy of a combined treatment of peptide vaccine therapy for advanced pancreatic cancer that has no effective treatment. During this trial, there were inquiries from 367 cases, of which 145 cases (40%) were examined at our outpatient clinic. The purpose of this study was to examine these cases in detail and to consider the points to be noted in executing clinical trials for poor prognosis cases. Methods: We examined the timing of inquiry, medical condition, the person(s) they inquired, and other relevant information regarding the 367 subjects who made inquiries. For the 145 cases visited the outpatient clinic of our hospital, we examined their medical condition, treatment and whether or not they have participated in a clinical trial. Results: 140 of the 367 cases (38%) of inquiry were concentrated within the first two months after the start. During these two months, there was a concentration of patients who had completed standard treatments and were a few months into BSC, but were unable to participate in the clinical trial due to deterioration of their general condition. Many of the inquiries were made by family members (spouse or child) of the patients, around twice the number of inquiries made by patients themselves. Even among the 145 subjects that were examined in the outpatient clinic of our hospital, severe cases, in particular, were seen several months after the start of the study. There were many cases that required urgent hospitalization during outpatient visits or patients whose general condition rapidly deteriorated during the screening tests. 23 cases (16%) underwent the clinical trial. Conclusions: In clinical trials such as this one, which handles cases with poor prognosis, many of the subjects are in poor general condition at the inquiry stage, and most of these inquiries are concentrated immediately after the start of the study. Therefore, it is very important to deal with inquiries and make judgments during the outpatient examination on whether or not clinical trial participation is possible.
Comprehensive analysis of tumor mutational load, genomic alterations, and PD-L1 status in gastrointestinal cancers using a multiplatform molecular profiling tool.
Authors: Giselle Alexandra Suero-Abreu, Miguel Gonzalez Velez, Marshall McKenna, Narjust Duma, Sejal Kothadia, Shalini R Krishnasamy, Janice Liu, Ning Dong, Umar Sharif Khawaja, Daniel Pievsky, Tracy Ann Proverbs-Singh, Martin Gutierrez
Journal: Journal of Clinical Oncology (2018)

93 Background: Tumor mutational load (TML) has been proposed as a biomarker of responsiveness to novel immune checkpoint inhibitors (ICIs) due its association with increased neoantigen formation and tumor immunogenicity. Gastrointestinal cancers (GICs) are generally insensitive to ICIs; therefore the aim of this study was to evaluate the TML, clinically relevant genomic alterations (CRGAs), and PDL-1 status of GIC patients (pts). Methods: We analyzed samples of pts with GICs using a multiplatform profiling tool (Caris Life Sciences, Phoenix, AZ). TML and CRGAs were calculated based on next generation sequencing and mutational load was stratified as high (≥17 mut/Mb), intermediate (8-16 mut/Mb), and low (≤ 7 mut/Mb). PD-L1 status was determined by IHC. Descriptive statistics and simple linear regression were used for analysis. Results: A total of 85 pts with GICs were analyzed. The median pt age was 65. 53% were males and 47% were females. Tumors were colorectal 51%, pancreatic 13%, esophageal 13%, gastric 9%, hepatobiliary 11%, anal canal 4%, and small intestine 1%. 80 cases (94%) had an adequate sample for profiling and TML was available in 59 cases (74%). Cases were 5% TML-high, 56% TML-intermediate, and 39% TML-low. The median TML was 9 mut/Mb and median CRGAs was 3. The most commonly detected CRGAs were TP53 (56%), APC (44%), KRAS (40%), ATM (18%) and PTEN (6%). A positive but very weak correlation was found between TML and number of CRGAs (R 2 = 0.3). PD-L1 status was available in 74 cases (93%) with 86% being PD-L1 negative and 14% PD-L1 positive. PD-L1 expression was most commonly seen in esophageal (50%) and anal canal (30%) cancers. Among 57 tumors tested for both biomarkers, no correlation was found between a high TML and PD-L1 expression. Conclusions: TML varies among GICs, and higher TML scores were not associated with PD-L1 expression, but there was a weak correlation between TML and the number of CRGAs. Further analysis by stratification of GIC type and prognostic analysis to assess the correlation between TMB and response to ICIs is warranted.
Developing trust with work colleagues
Authors: Mark Griffiths
Journal: BMJ (2006)

Trust is essential when building relationships. Whether it is with your line managers, colleagues, or patients, trust cannot be taken for granted. Here are some tips on how to develop trust at work.

Trust has to be earned —Unlike many things in life, trust depends on the perception of others and is something that we can't always control. Like respect, trust has to be earned

Be consistent in your …
USEFULNESS OF PREOPERATIVE N-TERMINAL PRO-B-TYPE NATRIURETIC PEPTIDE TO PREDICT NEW-ONSET ARRHYTHMIA AFTER SURGICAL VENTRICULAR SEPTAL MYECTOMY
Authors: Ying Guo, Xi Wu, Changpeng Song, Bing Tang, Xinxin Zheng, Jie Lu, Xiaonan Fang, Hao Cui, Shuiyun Wang, Xiaohong Huang
Journal: Journal of the American College of Cardiology (2018)
Prognostic significance of nutritional risk index in patients with metastatic esophageal squamous cell cancer.
Authors: Hiromichi Shirasu, Takahiro Tsushima, Mitsuhiro Furuta, Masahiro Kawahira, Takeshi Kawakami, Yukio Yoshida, Sadayuki Kawai, Satoshi Hamauchi, Akiko Todaka, Nozomu Machida, Tomoya Yokota, Kentaro Yamazaki, Akira Fukutomi, Yusuke Onozawa, Hirofumi Yasui
Journal: Journal of Clinical Oncology (2018)

156 Background: It has been suggested that nutritional indicators predict the prognosis of esophageal cancer. Nutritional risk (NR) as prognostic factor evaluated by NR index (NRI) in metastatic esophageal squamous cell cancer (ESCC) has not been clarified. Methods: We retrospectively reviewed the data of consecutive patients (pts) with metastatic ESCC who received chemotherapy (CTx) as initial treatment at Shizuoka Cancer Center between April 2008 and December 2015. The selection criteria were as follows: histologically confirmed squamous cell carcinoma; no indication for curative resection or definitive chemoradiotherapy (dCRT); adequate organ function; no prior CTx, radiotherapy (RT) or chemoradiotherapy; no other advanced malignancies. NR was calculated by following formula: NRI = (1.489*serum albumin) + (41.7*present body weight [BW] / ideal BW). NR was classified into 4 groups according to NRI: major (NRI &lt; 83.5), moderate (NRI = 83.5-97.5), mild (NRI = 97.5-100), none (NRI &gt; 100). Multivariate analysis was carried out using cox proportional hazard to estimate the hazard ratio for overall survival (OS). Results: The patients’ characteristics of 138 pts who met the selection criteria were as follows: median age (range), 67 (33-86) years; male/female, 123/15; performance status (PS) 0/1/2, 62/68/8; number of metastatic sites 1/2/3/4, 55/56/23/4; smoking history -/+, 19/119; previous esophagectomy -/+, 118/20; median skeletal muscle index (range), 44.5 (27.8-63.2); median body mass index (range), 20.3 (14.3-27.4); NR major/moderate/mild/none 22/37/26/53; median serum C-reactive protein (CRP) level (range), 0.75 (0.01-20.48) mg/dL. The most common chemotherapy regimen used was fluoropyrimidine plus cisplatin (93%), and 70 patients (50%) received concomitant RT. Median OS was 4.6 months in pts with major NR and 11.8 months in others (p &lt; 0.001). Multivariate analysis for OS identified PS 2, female sex, metastatic sites &gt; 2, CRP ≥ 1mg/dL, and major NR independently associated with poor survival. Conclusions: Major NR calculated by NRI formula associated with poor survival in pts with metastatic ESCC.
Abstract 16615: Reconstitution of CD4 T Cells Causes Cardiac Fibrosis and Myocardial Dysfunction in T Cell Specific S1P Receptor 1 Deficient Diabetic Mice
Authors: Chowdhury S Abdullah, Zhu-Qiu Jin
Journal: Circulation (2015)

Involvement of T cells in fibrosis has been reported but modulation of their role in context of diabetic fibrogenesis has yet to be determined. Our previous studies indicated that T cell S1P receptor 1 (S1P1) genetic depletion ensues sustained lymphopenia in circulation and reduced fibrosis in streptozotocin-induced type 1 murine diabetic model. We hypothesized that adoptive transfer of T cells to T-cell S1P1 receptor knock-out (TS1P1KO) mice would abolish cardioprotection and antifibrotic effect as observed earlier. TS1P1KO and littermate wild-type (WT) mice were divided into vehicle and streptozotocin (STZ) (50 mg/kg body weight for five days, i.p.) groups. Naïve CD4 T cells were isolated by positive selection through MS column from CD4 magnetic microbeads-labeled WT mice splenocytes. Isolated CD4 T cells (purity &gt;95%) were adoptively transferred (i.v.) into the mice of above groups at dose of one million cells. Body weight (g) and blood glucose level (mg/dl) were monitored. CD4 and CD8 T cells in blood were counted by flow cytometry. Heart histology was studied in H&amp;E stained sections and pathological grading was given. Masson Trichrome stained heart sections were digitally imaged at 16x magnification and percent of fibrotic area was quantified by using NIH ImageJ. Cardiac contractility was measured in ex-vivo Langendorff’s heart perfusion system at the end of 11 weeks. TS1P1KO mice had ~90% reduced T cells (CD4 cells: 1.15±0.30% vs 25.06±0.64%, CD8 cells: 2.09±0.42% vs 14.72±0.38% in WT, **P&lt;0.01, n=4-5) in blood. KO diabetic mice without adoptive transfer of CD4 T cells exhibited about 70% less fibrotic area (11.86±4.34% vs 46.48±8.06% in WT STZ, *P&lt;0.05, n=7-9) and improved cardiac structure and function. Adoptively CD4 T cells recipient KO diabetic mice presented cardiac structural disorganization (histological score: 9.25±0.95 vs. 1.29±0.52 in KO STZ without transfer, *P&lt;0.05, n=4-7) and increased myocardial fibrosis (37.11±3.22% vs. 11.86±4.34% in KO STZ without transfer, *P&lt;0.05, n=4-7) with reduced cardiac contractile force compared with KO diabetic mice without CD4 T cells transfer. In conclusion, reconstitution of CD4 T cells increases cardiac fibrosis and attenuates cardiac function in lymphopenic T cell S1P1 knock-out diabetic mice.
Eighteen doctors were struck off for sexual assault or rape in past four years
Authors: Abi Rimmer
Journal: BMJ (2018)

Between 2014 and 2017 the UK General Medical Council struck off 18 doctors for sexual assault or rape, show figures obtained by The BMJ . The data, which the GMC provided in response to a freedom of information request, do not specify whether the victims of the assaults were patients or other doctors.

Of the 18 erasures, 16 followed Medical Practitioners Tribunal Service hearings for allegations of sexual assault: four in …
Encoding of Self‐Referential Pain Catastrophizing in the Posterior Cingulate Cortex in Fibromyalgia
Authors: Jeungchan Lee, Ekaterina Protsenko, Asimina Lazaridou, Olivia Franceschelli, Dan‐Mikael Ellingsen, Ishtiaq Mawla, Kylie Isenburg, Michael P. Berry, Laura Galenkamp, Marco L. Loggia, Ajay D. Wasan, Robert R. Edwards, Vitaly Napadow
Journal: Arthritis & Rheumatology (2018)

Pain catastrophizing is a common feature of chronic pain, including fibromyalgia (FM), and is strongly associated with amplified pain severity and disability. While previous neuroimaging studies have focused on evoked pain response modulation by catastrophizing, the brain mechanisms supporting pain catastrophizing itself are unknown. We designed a functional magnetic resonance imaging (fMRI)-based pain catastrophizing task whereby patients with chronic pain engaged in catastrophizing-related cognitions. We undertook this study to test our hypothesis that catastrophizing about clinical pain would be associated with amplified activation in nodes of the default mode network (DMN), which encode self-referential cognition and show altered functioning in chronic pain.During fMRI, 31 FM patients reflected on how catastrophizing (CAT) statements (drawn from the Pain Catastrophizing Scale) impact their typical FM pain experience. Response to CAT statements was compared to response to matched neutral (NEU) statements.During statement reflection, higher fMRI signal during CAT statements than during NEU statements was found in several DMN brain areas, including the ventral (posterior) and dorsal (anterior) posterior cingulate cortex (vPCC and dPCC, respectively). Patients' ratings of CAT statement applicability were correlated solely with activity in the vPCC, a main DMN hub supporting self-referential cognition (r = 0.38, P < 0.05). Clinical pain severity was correlated solely with activity in the dPCC, a PCC subregion associated with cognitive control and sensorimotor processing (r = 0.38, P < 0.05).These findings provide evidence that the PCC encodes pain catastrophizing in FM and suggest distinct roles for different PCC subregions. Understanding the brain circuitry encoding pain catastrophizing in FM will prove to be important in identifying and evaluating the success of interventions targeting negative affect in chronic pain management.
Colorectal Tumors Require NUAK1 for Protection from Oxidative Stress
Authors: Jennifer Port, Nathiya Muthalagu, Meera Raja, Fatih Ceteci, Tiziana Monteverde, Björn Kruspig, Ann Hedley, Gabriela Kalna, Sergio Lilla, Lisa Neilson, Martina Brucoli, Katarina Gyuraszova, Jacqueline Tait-Mulder, Mokdad Mezna, Silvija Svambaryte, Amy Bryson, David Sumpton, Allan McVie, Colin Nixon, Martin Drysdale, Hiroyasu Esumi, Graeme I. Murray, Owen J. Sansom, Sara R. Zanivan, Daniel J. Murphy
Journal: Cancer Discovery (2018)

Abstract Exploiting oxidative stress has recently emerged as a plausible strategy for treatment of human cancer, and antioxidant defenses are implicated in resistance to chemotherapy and radiotherapy. Targeted suppression of antioxidant defenses could thus broadly improve therapeutic outcomes. Here, we identify the AMPK-related kinase NUAK1 as a key component of the antioxidant stress response pathway and reveal a specific requirement for this role of NUAK1 in colorectal cancer. We show that NUAK1 is activated by oxidative stress and that this activation is required to facilitate nuclear import of the antioxidant master regulator NRF2: Activation of NUAK1 coordinates PP1β inhibition with AKT activation in order to suppress GSK3β-dependent inhibition of NRF2 nuclear import. Deletion of NUAK1 suppresses formation of colorectal tumors, whereas acute depletion of NUAK1 induces regression of preexisting autochthonous tumors. Importantly, elevated expression of NUAK1 in human colorectal cancer is associated with more aggressive disease and reduced overall survival. Significance: This work identifies NUAK1 as a key facilitator of the adaptive antioxidant response that is associated with aggressive disease and worse outcome in human colorectal cancer. Our data suggest that transient NUAK1 inhibition may provide a safe and effective means for treatment of human colorectal cancer via disruption of intrinsic antioxidant defenses. Cancer Discov; 8(5); 632–47. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 517
What do I need to do to secure an SHO post in the histopathology schools in the 2005 intake?
Authors: Carl Gray
Journal: BMJ (2004)

Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
Hearing loss with kanamycin treatment for multidrug-resistant tuberculosis in Bangladesh
Authors: Scott K. Heysell, Shahriar Ahmed, Md. Toufiq Rahman, Md. Wahiduzzaman Akhanda, A. Tucker Gleason, Andrew Ebers, Eric R. Houpt, Sayera Banu
Journal: European Respiratory Journal (2018)

World Health Organization (WHO) recommendations for multidrug-resistant tuberculosis (MDR-TB) include treatment for 8 months or more of an aminoglycoside, such as kanamycin, amikacin or capreomycin, or a shorter course of 4 months or more, depending on the susceptibility of the patient's Mycobacterium tuberculosis isolate to other drugs in the regimen [1]. Aminoglycosides can produce significant side-effects, including irreversible ototoxicity, estimated to occur in 25–60% of patients treated for MDR-TB, depending on methods of measurement [2–5]. Even if surviving to cure, MDR-TB treatment itself is impoverishing [6], while ototoxicity further limits a patient's ability to regain employment and may compound social isolation. High frequency hearing loss from kanamycin in MDR-TB treatment: not if, but when? <http://ow.ly/dLQb30hPD2d> icddr,b acknowledges with gratitude the commitment of the National Institutes of Health to its research efforts. icddr,b is also grateful to the Governments of Bangladesh, Canada, Sweden and the UK for providing core/unrestricted support. The authors also express their sincere gratitude to the authority of NIDCH for their continued support to the studies conducted by icddr,b.