tbuckley/cabot-search huggingface dataset:
Defibrillators Don’t Deliver in Dialysis
Authors: Rachel Kaplan, Rod Passman
Journal: Circulation (2019)

Patients undergoing dialysis have a high mortality rate, a large proportion of which has been attributed to sudden cardiac death (SCD). 1 This elevated risk is likely attributable to a confluence of arrhythmic triggers including electrolyte and fluid shifts, myocardial ischemia, and dialysis-induced hemodynamic stress superimposed on a vulnerable cardiac substrate of left ventricular hypertrophy, fibrosis, and autonomic dysregulation to name but a few of the many contributing factors. 1 Although the risk of SCD is higher in patients undergoing dialysis than in those with congestive heart failure, the former have been excluded or nominally enrolled in all previous trials of implantable defibrillators (ICDs) because competing risks were expected to lessen the benefit of the device. 1 The decision to exclude these patients may have been prescient, because cohort studies that evaluated the role of ICDs in patients undergoing dialysis have almost uniformly found no improvement in survival and high complication rates regardless of implant indication. 2,3However, because these studies by definition evaluated patients undergoing dialysis with contemporaneous indications for device implantation, no data existed on the utility of primary prevention ICDs in a dialysis population with a preserved left ventricular ejection fraction where the competing risk of death from nonarrhythmic cardiovascular causes is expected to be lower. 2It is in this context that the ICD2 trial (A Prospective Randomized Controlled Trial to Evaluate the Prevention of Sudden Cardiac Death Using Implantable Cardioverter Defibrillators in Dialysis Patients) provides important insights into this poorly understood yet growing population of patients.In this issue of Circulation, Jukema et al 4 present the first-ever randomized controlled trial of ICDs in patients undergoing dialysis.Patients on chronic hemo-or peritoneal dialysis with a left ventricular ejection fraction ≥35% were randomly assigned to receive a transvenous ICD or no device therapy and followed for a median of 6.8 years.After enrolling 188 of the planned 200 patients over a 10year period, the trial was terminated for futility.The cumulative death rate was just >50% and similar in both groups, whereas the incidence of the primary end point of SCD was 9.7% in the ICD group and 7.9% in the control despite 13.8% of the ICD recipients receiving appropriate therapy for ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]).As has been seen with other device studies in this population, the complication rates were high and dominated by infection and lead failure.First and foremost, the authors are to be commended for the design and execution of a critically important study in a patient population too frequently ignored in cardiovascular trials.The fact that it took >10 years to enroll 188 patients is a testament to both the perseverance of the authors and the challenges of enrolling patients who are undergoing dialysis in such trials.The
Abstract 15098: Multimorbidity and Functional Limitation in Patients With Heart Failure: A Prospective Community Study
Authors: Sheila M Manemann, Alanna M Chamberlain, Veronique L Roger, Susan A Weston, Ruoxiang Jiang, Lila J Finney Rutten
Journal: Circulation (2017)

Background: Multimorbidity and functional limitation are associated with increased healthcare utilization in heart failure (HF). However, the individual and combined effect of these has not been we...
Lack of Standardized Terminology in Ultrasound Reports for Ovarian Cysts
Authors: Elizabeth Suh-Burgmann, Lisa Herrinton
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine 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 Internal Medicine journal
Hypoxia Induces Drug Resistance in Colorectal Cancer through the HIF-1α/miR-338-5p/IL-6 Feedback Loop
Authors: Ke Xu, Yueping Zhan, Zeting Yuan, Yanyan Qiu, Haijing Wang, Guohua Fan, Jie Wang, Wei Li, Yijun Cao, Xian Shen, Jun Zhang, Xin Liang, Peihao Yin
Journal: Molecular Therapy (2019)

Hypoxia is associated with poor prognosis and therapeutic resistance in cancer patients. Accumulating evidence has shown that microRNA (miRNA) plays an important role in the acquired drug resistance in colorectal carcinoma (CRC). However, the role of miRNA in hypoxia-induced CRC drug resistance remains to be elucidated. Here, we identified a hypoxia-triggered feedback loop that involves hypoxia-inducible transcription factor 1α (HIF-1α)-mediated repression of miR-338-5p and confers drug resistance in CRC. In this study, the unbiased miRNA array screening revealed that miR-338-5p is downregulated in both hypoxic CRC cell lines tested. Repression of miR-338-5p was required for hypoxia-induced CRC drug resistance. Furthermore, we identified interleukin-6 (IL-6), which mediates STAT3/Bcl2 activation under hypoxic conditions, as a direct miR-338-5p target. The resulting HIF-1α/miR-338-5p/IL-6 feedback loop was necessary for drug resistance in colon cancer cell lines. Using CRC patient samples, we found miR-338-5p has a negative correlation with HIF-1α and IL-6. Finally, in a xenograft model, overexpressing miR-338-5p in CRC cells and HIF-1α inhibitor PX-478 were able to enhance the sensitivity of CRC to oxaliplatin (OXA) via suppressing the HIF-1α/miR-338-5p/IL-6 feedback loop in vivo. Taken together, our results uncovered an HIF-1α/miR-338-5p/IL-6 feedback circuit that is critical in hypoxia-mediated drug resistance in CRC; targeting each member of this feedback loop could potentially reverse hypoxia-induced drug resistance in CRC.
Parathyroid Glands Hyperplasias Mimicking Medullary Thyroid Carcinoma Metastatic Lymph Nodes on 18F-DOPA PET/CT
Authors: Marie Terroir, Serena Grimaldi, Dana Hartl, Sophie Leboulleux, Désirée Deandreis
Journal: Clinical Nuclear Medicine (2019)

Abstract A pre operatory assessment by neck US, 18 F-DOPA and 18 F-choline PET/CT was performed in a 43-year-old MEN 2A woman affected by hyperparathyroidism and medullary thyroid carcinoma (MTC). On 18 F-DOPA, two thyroid uptakes were analyzed as multifocal MTC and two others in the central neck compartment as MTC metastatic lymph nodes. After surgery, multifocal intra thyroidal MTC and two parathyroid glands hyperplasias were proved without MTC adenopathies. We report a case of rare false positive uptake on 18 F-DOPA. In case of several endocrine diseases coexistence as in MEN 2A, 18 F-DOPA should be carefully analyzed.
IL-13–induced intestinal secretory epithelial cell antigen passages are required for IgE-mediated food-induced anaphylaxis
Authors: Taeko K. Noah, Kathryn A. Knoop, Keely G. McDonald, Jenny K. Gustafsson, Lisa Waggoner, Simone Vanoni, Matthew Batie, Kavisha Arora, Anjaparavanda P. Naren, Yui-Hsi Wang, Nicholas W. Lukacs, Ariel Munitz, Michael A. Helmrath, Maxime M. Mahe, Rodney D. Newberry, Simon P. Hogan
Journal: Journal of Allergy and Clinical Immunology (2019)
Business Strategies to Promote Health
Authors: Eli M. Cahan
Journal: JAMA (2019)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Dystopian levels of bureaucracy distract us from treating patients
Authors: Christopher A Efthymiou
Journal: BMJ (2019)

How long does induction take? Much longer than you think.1 How has it become that doctors rotating through new posts are subjected to dystopian levels of bureaucracy, in some cases having to repeat the process every four months?

At a time of major medical staff shortages, trainees are required to spend vital hours, and in some cases days, away from clinical practice to complete procedural, administrative, and often irrelevant …
Abstract 15685: Selective Improvement of Pulmonary Arterial Hypertension With Dual ETA/ETB Receptors Antagonist in the Apolipoprotein E-/- Model of PAH and Atherosclerosis
Authors: Nadine Arnold, Laura West, Adam Braithwaite, Rachel Walker, Mabrouka Alfaidi, Lewis Renshall, Janet Chamberlain, Helen Casbolt, Cathy Holt, Marc Iglarz, Sheila Francis, Allan Lawrie
Journal: Circulation (2016)

Introduction: Pulmonary arterial hypertension (PAH) is a devastating condition and without treatment is associated with a life expectancy of 2.8 years. Apolipoprotein E deficient (ApoE-/-) mice dev...
Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions
Authors: Kirsten Fischer, Othman Al-Sawaf, Jasmin Bahlo, Anna-Maria Fink, Maneesh Tandon, Mark Dixon, Sandra Robrecht, Simon Warburton, Kathryn Humphrey, Olga Samoylova, Anna M. Liberati, Javier Pinilla-Ibarz, Stephen Opat, Liliya Sivcheva, Katell Le Dû, Laura M. Fogliatto, Carsten U. Niemann, Robert Weinkove, Sue Robinson, Thomas J. Kipps, Sebastian Boettcher, Eugen Tausch, Rod Humerickhouse, Barbara Eichhorst, Clemens-Martin Wendtner, Anton W. Langerak, Karl-Anton Kreuzer, Matthias Ritgen, Valentin Goede, Stephan Stilgenbauer, Mehrdad Mobasher, Michael Hallek
Journal: New England Journal of Medicine (2019)

The BCL2 inhibitor venetoclax has shown activity in patients with chronic lymphocytic leukemia (CLL), but its efficacy in combination with other agents in patients with CLL and coexisting conditions is not known.In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil-obinutuzumab. The primary end point was investigator-assessed progression-free survival. The safety of each regimen was also evaluated.In total, 432 patients (median age, 72 years; median Cumulative Illness Rating Scale score, 8; median creatinine clearance, 66.4 ml per minute) underwent randomization, with 216 assigned to each group. After a median follow-up of 28.1 months, 30 primary end-point events (disease progression or death) had occurred in the venetoclax-obinutuzumab group and 77 had occurred in the chlorambucil-obinutuzumab group (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53; P<0.001). The Kaplan-Meier estimate of the percentage of patients with progression-free survival at 24 months was significantly higher in the venetoclax-obinutuzumab group than in the chlorambucil-obinutuzumab group: 88.2% (95% CI, 83.7 to 92.6) as compared with 64.1% (95% CI, 57.4 to 70.8). This benefit was also observed in patients with TP53 deletion, mutation, or both and in patients with unmutated immunoglobulin heavy-chain genes. Grade 3 or 4 neutropenia occurred in 52.8% of patients in the venetoclax-obinutuzumab group and in 48.1% of patients in the chlorambucil-obinutuzumab group, and grade 3 or 4 infections occurred in 17.5% and 15.0%, respectively. All-cause mortality was 9.3% in the venetoclax-obinutuzumab group and 7.9% in the chlorambucil-obinutuzumab group. These differences were not significant.Among patients with untreated CLL and coexisting conditions, venetoclax-obinutuzumab was associated with longer progression-free survival than chlorambucil-obinutuzumab. (Funded by F. Hoffmann-La Roche and AbbVie; ClinicalTrials.gov number, NCT02242942.).
Abstract 14382: Outcomes of Heart Transplantation in the Smallest Infants: To List or Let Grow?
Authors: Matthew J Bock, Elfriede Pahl, Osama Eltayeb, John M Costello, Jeffrey G Gossett
Journal: Circulation (2015)

Introduction: Waitlist and post-transplant outcomes for heart transplantation (HTx) in infants below 5 kg are not well defined. Hypothesis: We hypothesize that lower listing weight leads to higher waitlist and post-HTx mortality in the smallest infants. Methods: All children &lt;5 kg listed for primary (1°) HTx between 10/87-12/14 were identified in the United Network for Organ Sharing database. Demographic and clinical covariates, along with waitlist and post-HTx survival, were compared between weight groups. Waitlist and post-HTx survival differences were assessed via the Kaplan-Meier method and a Cox proportional hazards model assessed independent risk factors for mortality. Results: Over the 27 year study period, 2,785 infants &lt;5 kg were listed for 1° HTx. Median waiting time was 25 days [IQR 9-57]. The majority had congenital heart disease (79%) and 205 (7%) were &lt;2.5 kg. Waitlist death or removal due to deterioration was more common in infants &lt;2.5 kg (37%), compared to 31% in those 2.5-5 kg (p &lt;0.01). Waitlist survival was worse for patients with progressively lower listing weight (p &lt;0.01; Fig. 1a). In addition, 30-day and 1-year post-HTx survival were worse in the &lt;2.5 kg cohort [77%, 64% (&lt;2.5 kg) vs. 89%, 79% (2.5-5 kg), respectively] (p &lt;0.01; Fig. 1b). However, 1-year conditional survival after HTx was not different between the groups (p=0.82; Fig. 1c). In the &lt;2.5 kg group, pre-HTx ECMO requirement was an independent risk factor for waitlist and post-HTx mortality [waitlist adjusted HR 4.3 (CL 2.0, 9.2), post-HTx adjusted HR 11.3 (CL 4.0, 31.8); p &lt;0.01]. Conclusions: For small infants, lower listing weight is associated with increasing waitlist mortality. Early post-HTx mortality is worse for infants weighing &lt;2.5 kg and the need for ECMO while listed greatly increases these risks. Despite elevated waitlist and early post-HTx mortality, long term conditional survival for infants &lt;2.5 kg is similar to that achieved in patients weighing 2.5-5 kg.
Double-guidewire technique facilitates endoscopic ultrasound-guided biliary drainage for hilar biliary obstruction
Authors: Hirotoshi Ishiwatari, Tatsunori Satoh, Junya Sato, Junichi Kaneko, Hiroyuki Matsubayashi, Hiroyuki Ono
Journal: Endoscopy (2019)

A 74-year-old woman with a 2-year history of pancreaticoduodenectomy for pancreatic cancer was admitted to our hospital for treatment of obstructive jaundice due to a recurrent tumor, which divided the right and left hepatic ducts (RHD and LHD, respectively). Endoscopic ultrasound-guided biliary drainage (EUS-BD) was planned.
A Case of Sarcoidosis After Lymphoma
Authors: Aurélie Bando-Delaunay, Marie Luporsi, Virginie Huchet, Thibaut Cassou-Mounat, Nina Jehanno
Journal: Clinical Nuclear Medicine (2019)

Abstract We report the case of a 62-year-old woman with previous history of stage III Hodgkin lymphoma. Routine follow-up CT scan revealed 2 years after end of treatment the appearance of mediastinal nodes, suspected of lymphoma recurrence. An 18 F-FDG PET/CT was performed showing hypermetabolic mediastinal lymph nodes with diffuse symmetric osteomedullar hypermetabolism of pelvis and scapulae. In the hypothesis of either recurrence or multisystemic inflammatory disorder, bone marrow and lymph node biopsies were performed, revealing the presence of noncaseating epithelioid cell granulomas, leading to the diagnosis of multisystemic sarcoidosis. This case illustrates the sarcoidosis-lymphoma syndrome.
Acute pulmonary and hematological effects of two types of particles surrogates varies with their elemental composition
Authors: N. Medeiros Junior, P. H. N. Saldiva, D. H. F. R. Rivero, D. I. Kasahara, V. L. Capelozzi, J. J. Godleski, P. Koutrakis, L. Antonangelo
Journal: American Journal of Respiratory and Critical Care Medicine (2003)
Abstract #391: HS-1200, a synthetic bile acid derivative, induces autophagy formation in human hepatoma cells
Authors: Sang Eun Park, Min Young Kim, Mohammad Akbar Hossain, Dong Hwan Kim, Jin-Ah Kim, Gi Young Kim, Yung Hyun Choi, Nam Deuk Kim
Journal: Cancer Research (2009)

During the past several years, we have demonstrated that synthetic bile acid derivatives induce apoptosis in several human cancer cells. It is also used as mediators of cell cycle modulation in different cancer cells. In this study, we demonstrated that one of the synthetic bile acid derivatives, HS-1200, induced a strong cytotoxic effect toward HepG2 and Hep3B human hepatocellular carcinoma cells. HS-1200 showed cytotoxic effects on both cells in concentration-dependent manners. However, high doses of HS-1200 (25-100 µM) induced apoptotic cell death in both hepatoma cells, as evidenced by increases in the expressions of Bax and DNA fragmentation. On the other hand, both cells treated with low concentrations of HS-1200 (1-20 µM), which concentration range does not show apoptotic cell death in both hepatoma cells, revealed LC3-GFP aggregation of autophagocytic death. The treated hepatoma cells showed increased levels of beclin-1 and LC3-II proteins, specific markers of autophagy. The levels of Bcl-2 and p-Akt that have been implicated in the down-regulation of autophagy were decreased upon HS-1200 treatment in a concentration-dependent manner. Taken together, these findings indicate that HS-1200 induced cell death in HepG2 cells via two distinct anti-neoplastic activities of HS-1200, the ability to induce apoptosis and autophagy, therefore, suggesting that it may provide leverage to treat human liver cancer. This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD), Basic Research Promotion Fund) (KRF-2007-313-E00603).  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 391.
Genome Editing of Expanded CTG Repeats within the Human DMPK Gene Reduces Nuclear RNA Foci in the Muscle of DM1 Mice
Authors: Mirella Lo Scrudato, Karine Poulard, Célia Sourd, Stéphanie Tomé, Arnaud F. Klein, Guillaume Corre, Aline Huguet, Denis Furling, Geneviève Gourdon, Ana Buj-Bello
Journal: Molecular Therapy (2019)

Myotonic dystrophy type 1 (DM1) is caused by a CTG repeat expansion located in the 3′ UTR of the DMPK gene. Expanded DMPK transcripts aggregate into nuclear foci and alter the function of RNA-binding proteins, leading to defects in the alternative splicing of numerous pre-mRNAs. To date, there is no curative treatment for DM1. Here we investigated a gene-editing strategy using the CRISPR-Cas9 system from Staphylococcus aureus (Sa) to delete the CTG repeats in the human DMPK locus. Co-expression of SaCas9 and selected pairs of single-guide RNAs (sgRNAs) in cultured DM1 patient-derived muscle line cells carrying 2,600 CTG repeats resulted in targeted DNA deletion, ribonucleoprotein foci disappearance, and correction of splicing abnormalities in various transcripts. Furthermore, a single intramuscular injection of recombinant AAV vectors expressing CRISPR-SaCas9 components in the tibialis anterior muscle of DMSXL (myotonic dystrophy mouse line carrying the human DMPK gene with >1,000 CTG repeats) mice decreased the number of pathological RNA foci in myonuclei. These results establish the proof of concept that genome editing of a large trinucleotide expansion is feasible in muscle and may represent a useful strategy to be further developed for the treatment of myotonic dystrophy. Myotonic dystrophy type 1 (DM1) is caused by a CTG repeat expansion located in the 3′ UTR of the DMPK gene. Expanded DMPK transcripts aggregate into nuclear foci and alter the function of RNA-binding proteins, leading to defects in the alternative splicing of numerous pre-mRNAs. To date, there is no curative treatment for DM1. Here we investigated a gene-editing strategy using the CRISPR-Cas9 system from Staphylococcus aureus (Sa) to delete the CTG repeats in the human DMPK locus. Co-expression of SaCas9 and selected pairs of single-guide RNAs (sgRNAs) in cultured DM1 patient-derived muscle line cells carrying 2,600 CTG repeats resulted in targeted DNA deletion, ribonucleoprotein foci disappearance, and correction of splicing abnormalities in various transcripts. Furthermore, a single intramuscular injection of recombinant AAV vectors expressing CRISPR-SaCas9 components in the tibialis anterior muscle of DMSXL (myotonic dystrophy mouse line carrying the human DMPK gene with >1,000 CTG repeats) mice decreased the number of pathological RNA foci in myonuclei. These results establish the proof of concept that genome editing of a large trinucleotide expansion is feasible in muscle and may represent a useful strategy to be further developed for the treatment of myotonic dystrophy.
影响 BCC 后低阶随访护理的因素
Authors: S. Egmond, M. Wakkee, A. Rengen, M.T. Bastiaens, T. Nijsten, M. Lugtenberg
Journal: British Journal of Dermatology (2019)

基底细胞癌(BCC)是全世界最常见的癌症,而且其发生率仍不断上升。它是一种皮肤癌,但通常生长缓慢,而且极少在其他身体部位蔓延。目前,治疗指南推荐仅根据某些因素(如肿瘤大小、位置及其生长速度是否异常快)向“高危”BCC患者提供随访护理(如年检)。但皮肤科医生仍然也向低危BCC患者提供随访护理。为了解提供这种所谓的“低阶护理”的原因以及确定减少这种护理的策略,荷兰鹿特丹作者访问了 18 名皮肤科医生,并组织了3个焦点小组,其中有17名低危BCC患者。这些访问和焦点小组全部进行录音,并逐字转抄。然后将抄录内容载入软件程序,并进行主题分析。皮肤科医生提供低阶随访护理的 2 个主要原因是:i) 符合患者首选项,以及 ii) 不相信全科医师 (GP) 对可疑病灶的鉴定(可能皮肤癌)。财务激励和习惯是 2 个进一步原因。患者也表示对GP缺乏信任,然而某些BCC患者首选接受定期随访护理,而有些患者觉得不需要。建议了多个减少随访护理的策略,其中皮肤科医生和患者认为教育患者潜在有效。一项预研究纳入了本次研究结果,其中BCC患者收到许多书面信息,包括其疾病、治疗、复发几率和随后BCC几率的信息。这些书面信息将根据患者的特定情况进行定制。