tbuckley/cabot-search huggingface dataset:
Laparoscopic Versus Open Gastrectomy for Gastric Cancer (LOGICA): A Multicenter Randomized Clinical Trial
Authors: Arjen van der Veen, Hylke J. F. Brenkman, Maarten F. J. Seesing, Leonie Haverkamp, Misha D. P. Luyer, Grard A. P. Nieuwenhuijzen, Jan H. M. B. Stoot, Juul J. W. Tegels, Bas P. L. Wijnhoven, Sjoerd M. Lagarde, Wobbe O. de Steur, Henk H. Hartgrink, Ewout A. Kouwenhoven, Eelco B. Wassenaar, Werner A. Draaisma, Suzanne S. Gisbertz, Donald L. van der Peet, Anne M. May, Jelle P. Ruurda, Richard van Hillegersberg, Anne M. Eligh, Jeroen E. H. Ponten, Fanny F. B. M. Heesakkers, Karel W. E. Hulsewe, Thais T. T. Tweed, Jan J. B. van Lanschot, Marc J. van Det, P. van Duijvendijk, Edwin S. van der Zaag, Ivo A. M. J. Broeders, Mark I. van Berge Henegouwen, Wietse J. Eshuis, Freek Daams, David J. Heineman, Hanneke W. M. van Laarhoven
Journal: Journal of Clinical Oncology (2021)

The oncological efficacy and safety of laparoscopic gastrectomy are under debate for the Western population with predominantly advanced gastric cancer undergoing multimodality treatment.In 10 experienced upper GI centers in the Netherlands, patients with resectable (cT1-4aN0-3bM0) gastric adenocarcinoma were randomly assigned to either laparoscopic or open gastrectomy. No masking was performed. The primary outcome was hospital stay. Analyses were performed by intention to treat. It was hypothesized that laparoscopic gastrectomy leads to shorter hospital stay, less postoperative complications, and equal oncological outcomes.Between 2015 and 2018, a total of 227 patients were randomly assigned to laparoscopic (n = 115) or open gastrectomy (n = 112). Preoperative chemotherapy was administered to 77 patients (67%) in the laparoscopic group and 87 patients (78%) in the open group. Median hospital stay was 7 days (interquartile range, 5-9) in both groups (P = .34). Median blood loss was less in the laparoscopic group (150 v 300 mL, P < .001), whereas mean operating time was longer (216 v 182 minutes, P < .001). Both groups did not differ regarding postoperative complications (44% v 42%, P = .91), in-hospital mortality (4% v 7%, P = .40), 30-day readmission rate (9.6% v 9.1%, P = 1.00), R0 resection rate (95% v 95%, P = 1.00), median lymph node yield (29 v 29 nodes, P = .49), 1-year overall survival (76% v 78%, P = .74), and global health-related quality of life up to 1 year postoperatively (mean differences between + 1.5 and + 3.6 on a 1-100 scale; 95% CIs include zero).Laparoscopic gastrectomy did not lead to a shorter hospital stay in this Western multicenter randomized trial of patients with predominantly advanced gastric cancer. Postoperative complications and oncological efficacy did not differ between laparoscopic gastrectomy and open gastrectomy.
Outcome of limited‐stage peripheral <scp>T‐Cell</scp> lymphoma after <scp>CHOP</scp> (−like) therapy: A population based study of 239 patients from the Nordic lymphoma epidemiology group
Authors: Ahmed Ludvigsen Al-Mashhadi
Journal: American Journal of Hematology (2023)

Peripheral T-Cell Lymphomas (PTCLs) are rare, aggressive lymphomas with poor outcomes, but limited-stage disease is infrequent and not well-described. This study reports outcomes and prognostic factors in limited-stage nodal PTCLs in a binational population-based setting. Patients were identified from the Danish and Swedish lymphoma registries. Adults diagnosed with limited-stage nodal PTCL (stage I-II) and treated with CHOP(-like) therapy ±radiotherapy between 2000 and 2014 were included. Medical records were reviewed by local investigators. A total of 239 patients with a median age of 62 years were included; 67% received 6-8 cycles of CHOP(-like) therapy and 22% received 3-4 cycles, of which 59% also received radiotherapy. Autologous stem cell transplant consolidation was administered to 16% of all patients. Median follow-up was 127 months with 5-years overall survival (OS) of 58% (95% CI: 53-65) and progression-free survival (PFS) of 53% (95% CI: 47-59). In multivariable analysis, age ≥ 60 years and B-symptoms were unfavorable and ALK+ anaplastic large cell T-Cell lymphoma was favorable for survival outcomes. There was no difference in treatment-specific outcome (3-4 cycles vs. 6-8 cycles of CHOP(-like) ± radiotherapy). Low-risk patients (age < 60 without B-symptoms) had a 5-year OS of 77% (95% CI 67-89%). In the present study of limited-stage nodal PTCL, survival after curative intent chemotherapy +/- radiotherapy was inferior to that of limited-stage diffuse large B-cell lymphoma, but a subgroup of young patients without B-symptoms had very good outcomes. Treatment outcomes after 3-4 cycles versus 6-8 cycles of CHOP(-like) therapy were comparable.
Stimulation of Contractility in Systolic Heart Failure
Authors: Karl Swedberg
Journal: New England Journal of Medicine (2021)

The treatment of patients with heart failure and reduced myocardial contractility (i.e., systolic failure) has been and remains a challenge. Increasing contractility by stimulation with pharmaceutical agents has consistently failed to improve outcomes and has often resulted in increased mortality.1 In contrast, treatments with no effect or even a negative effect on contractility — such as angiotensin-converting–enzyme inhibitors and beta-adrenergic receptor blockers — have been shown to improve outcomes. The harmful effect of previously studied inotropic agents has been shown to be related to the mechanism of action of these drugs; stimulation of contractility through modulation of myocardial cyclic AMP . . .
Abstract 12633: Use of Nicorandil is Associated With Increased Risk of Incident Atrial Fibrillation- A Population-based Nested Case-control Study and Molecular Studies to Explain the Association
Authors: Pang-shuo Huang, Chien-Chang Lee, Chia-Ying Chan, Kyle Rumery, Ke-Ying Su, Tze-Chun Hsu, Chia-Ti Tsai
Journal: Circulation (2020)

Background: Nicorandil is a potent vasodilator of coronary vessels through its effect on opening of ATP-sensitive potassium channel (KATP), and has been used as an antianginal agent. Activation of potassium channels play an important role in the mechanism of atrial fibrillation (AF) or atrial flutter (AFL). Accordingly, whether use of nicorandil might contribute to initiation and/or perpetuation of AF/AFL remained unknown. Objectives: To determine the relationship between use of nicorandil and risk of atrial fibrillation. Methods: We performed a nested case-control study using a cohort of 1 million people assembled from the National Health Insurance Research Database (NHIRD) of Taiwan. The association between nicorandil use and risk of atrial fibrillation was estimated by logistic regression model. We also performed molecular and cellular studies to explain the association. Results: A total of 715 individuals who experienced atrial fibrillation or atrial flutter were matched to 72,215 controls. To account for the potential unmeasured confounders, we identified nitrate users in the same cohort as an active comparator. After adjustment, new use of nicorandil was found to be associated with increased risk for atrial fibrillation or atrial flutter (odds ratio [OR], 2.34; 95% CI 1.07-5.13) compared to nitrate use. Activation of potassium channel shortens atrial action potential duration (APD), which subsequently perpetuates AF. Dysfunction of mutated sarcKATP channels in atrial cells may lead to electrical instability and atrial fibrillation. We found expression of KATP in human atrial tissues. Furthermore, nicorandil directly shortened APD and the QT interval of cultured induced pluripotent stem cell (iPSC) derived cardiomyocytes (iPSC-CMs). Conclusion: Use of nicorandil, especially new use, was found to be associated with increased risk of AF or AFL. We also first showed the expression of KATP in human atria and use of nicorandil may promote or increase the risk of AF through activation of KATP and shortening of atrial APD.
Returning to physical activity after covid-19
Authors: David Salman, Dane Vishnubala, Peter Le Feuvre, Thomas Beaney, Jonathan Korgaonkar, Azeem Majeed, Alison H McGregor
Journal: BMJ (2021)

<b>SUMMARY:</b> Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic state accompanied by a unique brain imaging pattern typically associated with a number of complex clinical conditions including: preeclampsia/eclampsia, allogeneic bone marrow transplantation, solid organ transplantation, autoimmune diseases and high dose cancer chemotherapy. The mechanism behind the developing vasogenic edema and CT or MR imaging appearance of PRES is not known. Two theories have historically been proposed: 1) Severe hypertension leads to failed auto-regulation, subsequent hyperperfusion, with endothelial injury/vasogenic edema and; 2) vasoconstriction and hypoperfusion leads to brain ischemia and subsequent vasogenic edema. The strengths/weaknesses of these hypotheses are reviewed in a translational fashion including supporting evidence and current available imaging/clinical data related to the conditions that develop PRES. While the hypertension/hyperperfusion theory has been most popular, the conditions associated with PRES have a similar immune challenge present and develop a similar state of T-cell/endothelial cell activation that may be the basis of leukocyte trafficking and systemic/cerebral vasoconstriction. These systemic features along with current vascular and perfusion imaging features in PRES appear to render strong support for the older theory of vasoconstriction coupled with hypoperfusion as the mechanism.
Partners and Pardners
Authors: Sydney Lea
Journal: JAMA (2021)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Analysis of an Ebola virus disease survivor whose host and viral markers were predictive of death indicates the effectiveness of medical countermeasures and supportive care
Authors: Andrew Bosworth, Natasha Y. Rickett, Xiaofeng Dong, Lisa F. P. Ng, Isabel García-Dorival, David A. Matthews, Tom Fletcher, Michael Jacobs, Emma C. Thomson, Miles W. Carroll, Julian A. Hiscox
Journal: Genome Medicine (2021)

Abstract Background Ebola virus disease (EVD) is an often-fatal infection where the effectiveness of medical countermeasures is uncertain. During the West African outbreak (2013–2016), several patients were treated with different types of anti-viral therapies including monoclonal antibody-based cocktails that had the potential to neutralise Ebola virus (EBOV). However, at the time, the efficacy of these therapies was uncertain. Given the scale of the outbreak, several clinical phenotypes came to the forefront including the ability of the same virus to cause recrudescence in the same patient—perhaps through persisting in immune privileged sites. Several key questions remained including establishing if monoclonal antibody therapy was effective in humans with severe EVD, whether virus escape mutants were selected during treatment, and what is the potential mechanism(s) of persistence. This was made possible through longitudinal samples taken from a UK patient with EVD. Methods Several different sample types, plasma and cerebrospinal fluid, were collected and sequenced using Illumina-based RNAseq. Sequence reads were mapped both to EBOV and the human genome and differential gene expression analysis used to identify changes in the abundance of gene transcripts as infection progressed. Digital Cell Quantitation analysis was used to predict the immune phenotype in samples derived from blood. Results The findings were compared to equivalent data from West African patients. The study found that both virus and host markers were predictive of a fatal outcome. This suggested that the extensive supportive care, and most likely the application of the medical countermeasure ZMab (a monoclonal antibody cocktail), contributed to survival of the UK patient. The switch from progression to a ‘fatal’ outcome to a ‘survival’ outcome could be seen in both the viral and host markers. The UK patient also suffered a recrudescence infection 10 months after the initial infection. Analysis of the sequencing data indicated that the virus entered a period of reduced or minimal replication, rather than other potential mechanisms of persistence—such as defective interfering genomes. Conclusions The data showed that comprehensive supportive care and the application of medical countermeasures are worth pursuing despite an initial unfavourable prognosis.
The biology, function, and applications of exosomes in cancer
Authors: Jinyi Liu, Liwen Ren, Sha Li, Wan Li, Xiangjin Zheng, Yihui Yang, Weiqi Fu, Jie Yi, Jinhua Wang, Guanhua Du
Journal: Acta Pharmaceutica Sinica B (2021)

Exosomes are cell-derived nanovesicles with diameters from 30 to 150 nm, released upon fusion of multivesicular bodies with the cell surface. They can transport nucleic acids, proteins, and lipids for intercellular communication and activate signaling pathways in target cells. In cancers, exosomes may participate in growth and metastasis of tumors by regulating the immune response, blocking the epithelial-mesenchymal transition, and promoting angiogenesis. They are also involved in the development of resistance to chemotherapeutic drugs. Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers. Because of their amphipathic structure, exosomes are natural drug delivery vehicles for cancer therapy.
Hypoxia downregulated miR-4521 suppresses gastric carcinoma progression through regulation of IGF2 and FOXM1
Authors: Shan Xing, Zhi Tian, Wenying Zheng, Wenjuan Yang, Nan Du, Yixue Gu, Jiang Yin, Hao Liu, Xiaoting Jia, Donglan Huang, Wanli Liu, Min Deng
Journal: Molecular Cancer (2021)

MicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, as they have been revealed as crucial modulators in tumor progression. However, our understanding of their roles in gastric carcinoma (GC) metastasis is limited. Here, we aimed to identify novel miRNAs involved in GC metastasis and explored their regulatory mechanisms and therapeutic significance in GC.
Equivalent DNA methylation variation between monozygotic co-twins and unrelated individuals reveals universal epigenetic inter-individual dissimilarity
Authors: Benjamin Planterose Jiménez, Fan Liu, Amke Caliebe, Diego Montiel González, Jordana T. Bell, Manfred Kayser, Athina Vidaki
Journal: Genome biology (2021)

Abstract Background Although the genomes of monozygotic twins are practically identical, their methylomes may evolve divergently throughout their lifetime as a consequence of factors such as the environment or aging. Particularly for young and healthy monozygotic twins, DNA methylation divergence, if any, may be restricted to stochastic processes occurring post-twinning during embryonic development and early life. However, to what extent such stochastic mechanisms can systematically provide a stable source of inter-individual epigenetic variation remains uncertain until now. Results We enriched for inter-individual stochastic variation by using an equivalence testing-based statistical approach on whole blood methylation microarray data from healthy adolescent monozygotic twins. As a result, we identified 333 CpGs displaying similarly large methylation variation between monozygotic co-twins and unrelated individuals. Although their methylation variation surpasses measurement error and is stable in a short timescale, susceptibility to aging is apparent in the long term. Additionally, 46% of these CpGs were replicated in adipose tissue. The identified sites are significantly enriched at the clustered protocadherin loci, known for stochastic methylation in developing neurons. We also confirmed an enrichment in monozygotic twin DNA methylation discordance at these loci in whole genome bisulfite sequencing data from blood and adipose tissue. Conclusions We have isolated a component of stochastic methylation variation, distinct from genetic influence, measurement error, and epigenetic drift. Biomarkers enriched in this component may serve in the future as the basis for universal epigenetic fingerprinting, relevant for instance in the discrimination of monozygotic twin individuals in forensic applications, currently impossible with standard DNA profiling.
BOTULISM. STUDIES ON THE MANNER IN WHICH THE TOXIN OF CLOSTRIDIUM BOTULINUM ACTS UPON THE BODY
Authors: Ernest C. Dickson, Eshref Shevky
Journal: The Journal of Experimental Medicine (1923)

1. In addition to the effect upon the fibers of the parasympathetic nervous system which was described in a previous report (1), the toxin of Clostridium botilinum. Types A and B, exerts an influence upon the endings of the motor fibers of the voluntary nervous system which leads to a marked susceptibility to fatigue. It has not been determined whether the damage is in the anatomical nerve endings of the somatic motor nerve fibers or upon the myoneural junction, but it is not of the nature of an organic destruction of tissue. 2. There is no effect upon the sensory fibers of the peripheral nerves. 3. The muscle cells of the smooth and striated muscles are not affected. 4. The disturbances in function which have been demonstrated in the voluntary and involuntary nervous systems fully explain the characteristic signs and symptoms of botulinus intoxication.
Left Atrial Size and Postoperative Atrial Fibrillation: The Volume of Evidence Suggests it Is Time to Break an Old Habit⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Warren J. Manning, Eli V. Gelfand
Journal: Journal of the American College of Cardiology (2006)
Use of proton pump inhibitors to treat persistent throat symptoms: multicentre, double blind, randomised, placebo controlled trial
Authors: James O’Hara, Deborah D Stocken, Gillian C Watson, Tony Fouweather, Julian McGlashan, Kenneth MacKenzie, Paul Carding, Yakubu Karagama, Ruth Wood, Janet A Wilson
Journal: BMJ (2021)

Abstract Objective To assess the use of proton pump inhibitors (PPIs) to treat persistent throat symptoms. Design Pragmatic, double blind, placebo controlled, randomised trial. Setting Eight ear, nose, and throat outpatient clinics, United Kingdom. Participants 346 patients aged 18 years or older with persistent throat symptoms who were randomised according to recruiting centre and baseline severity of symptoms (mild or severe): 172 to lansoprazole and 174 to placebo. Intervention Random blinded allocation (1:1) to either 30 mg lansoprazole twice daily or matched placebo twice daily for 16 weeks. Main outcome measures Primary outcome was symptomatic response at 16 weeks measured using the total reflux symptom index (RSI) score. Secondary outcomes included symptom response at 12 months, quality of life, and throat appearances. Results Of 1427 patients initially screened for eligibility, 346 were recruited. The mean age of the study sample was 52.2 (SD 13.7) years, 196 (57%) were women, and 162 (47%) had severe symptoms at presentation; these characteristics were balanced across treatment arms. The primary analysis was performed on 220 patients who completed the primary outcome measure within a window of 14-20 weeks. Mean RSI scores were similar between treatment arms at baseline: lansoprazole 22.0 (95% confidence interval 20.4 to 23.6) and placebo 21.7 (20.5 to 23.0). Improvements (reduction in RSI score) were observed in both groups—score at 16 weeks: lansoprazole 17.4 (15.5 to19.4) and placebo 15.6 (13.8 to 17.3). No statistically significant difference was found between the treatment arms: estimated difference 1.9 points (95% confidence interval −0.3 to 4.2 points; P=0.096) adjusted for site and baseline symptom severity. Lansoprazole showed no benefits over placebo for any secondary outcome measure, including RSI scores at 12 months: lansoprazole 16.0 (13.6 to 18.4) and placebo 13.6 (11.7 to 15.5): estimated difference 2.4 points (−0.6 to 5.4 points). Conclusions No evidence was found of benefit from PPI treatment in patients with persistent throat symptoms. RSI scores were similar between the lansoprazole and placebo groups after 16 weeks of treatment and at the 12 month follow-up. Trial registration ISRCTN Registry ISRCTN38578686 and EudraCT 2013-004249-17.
Deep learning-enabled medical computer vision
Authors: Andre Esteva, Katherine Chou, Serena Yeung, Nikhil Naik, Ali Madani, Ali Mottaghi, Yun Liu, Eric Topol, Jeff Dean, Richard Socher
Journal: npj Digital Medicine (2021)

Abstract A decade of unprecedented progress in artificial intelligence (AI) has demonstrated the potential for many fields—including medicine—to benefit from the insights that AI techniques can extract from data. Here we survey recent progress in the development of modern computer vision techniques—powered by deep learning—for medical applications, focusing on medical imaging, medical video, and clinical deployment. We start by briefly summarizing a decade of progress in convolutional neural networks, including the vision tasks they enable, in the context of healthcare. Next, we discuss several example medical imaging applications that stand to benefit—including cardiology, pathology, dermatology, ophthalmology–and propose new avenues for continued work. We then expand into general medical video, highlighting ways in which clinical workflows can integrate computer vision to enhance care. Finally, we discuss the challenges and hurdles required for real-world clinical deployment of these technologies.