tbuckley/cabot-search huggingface dataset:
Critical Role of Neprilysin in Kidney Angiotensin Metabolism
Authors: Christopher C. Kaltenecker, Oliver Domenig, Chantal Kopecky, Marlies Antlanger, Marko Poglitsch, Gabriela Berlakovich, Renate Kain, Johannes Stegbauer, Masudur Rahman, Roland Hellinger, Christian Gruber, Nadja Grobe, Harun Fajkovic, Farsad Eskandary, Georg A. Böhmig, Marcus D. Säemann, Johannes J. Kovarik
Journal: Circulation Research (2020)

Rationale: Kidney homeostasis is critically determined by the coordinated activity of the renin-angiotensin system (RAS), including the balanced synthesis of its main effector peptides Ang (angiotensin) II and Ang (1–7). The condition of enzymatic overproduction of Ang II relative to Ang (1–7) is termed RAS dysregulation and leads to cellular signals, which promote hypertension and organ damage, and ultimately progressive kidney failure. ACE2 (angiotensin-converting enzyme 2) and NEP (neprilysin) induce the alternative, and potentially reno-protective axis by enhancing Ang (1–7) production. However, their individual contribution to baseline RAS balance and whether their activities change in chronic kidney disease (CKD) has not yet been elucidated. Objective: To examine whether NEP-mediated Ang (1–7) generation exceeds Ang II formation in the healthy kidney compared with diseased kidney. Methods and Results: In this exploratory study, we used liquid chromatography-tandem mass spectrometry to measure Ang II and Ang (1–7) synthesis rates of ACE, chymase and NEP, ACE2, PEP (prolyl-endopeptidase), PCP (prolyl-carboxypeptidase) in kidney biopsy homogenates in 11 healthy living kidney donors, and 12 patients with CKD. The spatial expression of RAS enzymes was determined by immunohistochemistry. Healthy kidneys showed higher NEP-mediated Ang (1–7) synthesis than Ang II formation, thus displaying a strong preference towards the reno-protective alternative RAS axis. In contrast, in CKD kidneys higher levels of Ang II were recorded, which originated from mast cell chymase activity. Conclusions: Ang (1–7) is the dominant RAS peptide in healthy human kidneys with NEP rather than ACE2 being essential for its generation. Severe RAS dysregulation is present in CKD dictated by high chymase-mediated Ang II formation. Kidney RAS enzyme analysis might lead to novel therapeutic approaches for CKD.
Residual endotoxin induces primary graft dysfunction through ischemia-reperfusion-primed alveolar macrophages
Authors: Mahzad Akbarpour, Emilia Lecuona, Stephen Chiu, Qiang Wu, Melissa Querrey, Ramiro Fernandez, Felix Luis Nunez-Santana, Haiying Sun, Sowmya Ravi, Chitaru Kurihara, James M. Walter, Nikita Joshi, Ziyou Ren, Scott C. Roberts, Alan R. Hauser, Daniel Kreisel, Wenjun Li, Navdeep Chandel, Alexander V. Misharin, Thalachallour Mohanakumar, G.R. Scott Budinger, Ankit Bharat
Journal: Journal of Clinical Investigation (2020)

Despite the widespread use of antibiotics, bacterial pneumonias in donors strongly predispose to the fatal syndrome of primary graft dysfunction (PGD) following lung transplantation. We report that bacterial endotoxin persists in human donor lungs after pathogen is cleared with antibiotics and is associated with neutrophil infiltration and PGD. In mouse models, depletion of tissue-resident alveolar macrophages (TRAMs) attenuated neutrophil recruitment in response to endotoxin as shown by compartmental staining and intravital imaging. Bone marrow chimeric mice revealed that neutrophils were recruited by TRAM through activation of TLR4 in a MyD88-dependent manner. Intriguingly, low levels of endotoxin, insufficient to cause donor lung injury, promoted TRAM-dependent production of CXCL2, increased neutrophil recruitment, and led to PGD, which was independent of donor NCMs. Reactive oxygen species (ROS) increased in human donor lungs starting from the warm-ischemia phase and were associated with increased transcription and translocation to the plasma membrane of TLR4 in donor TRAMs. Consistently, scavenging ROS or inhibiting their production to prevent TLR4 transcription/translocation or blockade of TLR4 or coreceptor CD14 on donor TRAMs prevented neutrophil recruitment in response to endotoxin and ameliorated PGD. Our studies demonstrate that residual endotoxin after successful treatment of donor bacterial pneumonia promotes PGD through ischemia/reperfusion-primed donor TRAMs.
Balancing Past vs Future Values in Decision-making
Authors: Susan P. Shapiro
Journal: JAMA (2020)

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
Endoscopic ultrasound-guided gastroenterostomy with water-jet filling technique through a 19G needle to treat complete malignant duodenal obstruction
Authors: Anaëlle Collin, Sanaa Brahmia, Florian Rostain, Alexandru Lupu, Laura Calavas, Jérémie Jacques, Mathieu Pioche
Journal: Endoscopy (2020)

Duodenal self-expandable metal stenting is the most common treatment for duodenal malignant obstruction. However, when it is impossible to pass a guidewire through the obstruction, gastroenterostomy using a lumen-apposing metal stent (LAMS) is an effective alternative [1]. Nevertheless, it is commonly necessary to introduce a filling catheter to fill the bowel with water [2] or to place a guidance balloon [3].
Selective role of Nck1 in atherogenic inflammation and plaque formation
Authors: Mabruka Alfaidi, Christina H. Acosta, Dongdong Wang, James G. Traylor, A. Wayne Orr
Journal: Journal of Clinical Investigation (2020)

Although the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) established the role of treating inflammation in atherosclerosis, our understanding of endothelial activation at atherosclerosis-prone sites remains limited. Disturbed flow at atheroprone regions primes plaque inflammation by enhancing endothelial NF-κB signaling. Herein, we demonstrate a role for the Nck adaptor proteins in disturbed flow-induced endothelial activation. Although highly similar, only Nck1 deletion, but not Nck2 deletion, limited flow-induced NF-κB activation and proinflammatory gene expression. Nck1-knockout mice showed reduced endothelial activation and inflammation in both models, disturbed flow- and high fat diet-induced atherosclerosis, whereas Nck2 deletion did not. Bone marrow chimeras confirmed that vascular Nck1, but not hematopoietic Nck1, mediated this effect. Domain-swap experiments and point mutations identified the Nck1 SH2 domain and the first SH3 domain as critical for flow-induced endothelial activation. We further characterized Nck1's proinflammatory role by identifying interleukin 1 type I receptor kinase-1 (IRAK-1) as a Nck1-selective binding partner, demonstrating that IRAK-1 activation by disturbed flow required Nck1 in vitro and in vivo, showing endothelial Nck1 and IRAK-1 staining in early human atherosclerosis, and demonstrating that disturbed flow-induced endothelial activation required IRAK-1. Taken together, our data reveal a hitherto unknown link between Nck1 and IRAK-1 in atherogenic inflammation.
Abstract 10571: Triage HF Plus: Predicting, Preventing and Managing Heart Failure Episodes in Ambulatory Patients With a Cardiac Implantable Electronic Device Using Device Based Diagnostics and Automated Carelink Alerts
Authors: Fozia Z Ahmed, Joanne Taylor, Lucy Moore, Caroline Green, Manish Motwani, Colin C Cunnington, Salimah Hassan, Paula Black, Alison Seed
Journal: Circulation (2018)

Introduction: Changes in physiological parameters, such as thoracic impedance, arrhythmias, pacing percentage, diurnal heart rate variability and patient activity may precede clinical decompensatio...
Penile veneral edema
Authors: R. A. Wright
Journal: JAMA (1979)

A one-year epidemiologic study of penile venereal edema in a clinic for sexually transmitted diseases identified 25 cases, a rate of 1.7 per 1,000 male visits. Twenty-four patients had coexisting urethritis (36%), infected penile lesions (36%), or both (24%). Men with penile edema were significantly more likely to have gonococcal urethritis (40%), genital scabies (12%), genital herpes (12%), and inguinal adenopathy (52%) than men without penile edema. Penile edema is self-limited and seems to resolve along with the underlying penile disease. Lymphatic involvement may be the final common factor. (<i>JAMA</i>241:157-158, 1979)
Abstract 14796: Posttraumatic Stress Disorder is Associated With Mental Stress-Induced Myocardial Ischemia in Men and Women After a Recent Myocardial Infarction
Authors: Bruno B Lima, Muhammad Hammadah, Brad Pearce, Amit J Shah, Kasra Moazzami, Jeong Hwan Kim, Samaah Sullivan, Oleksiy Levantsevych, An Young, Tene T Lewis, Lisa Elon, Paolo Raggi, J. Douglas Bremner, Arshed A Quyyumi, Viola Vaccarino
Journal: Circulation (2019)

Introduction: Posttraumatic Stress Disorder (PTSD) is prevalent among patients who survived an acute myocardial infarction (MI), and is associated with adverse outcomes, but the mechanisms remain u...
Improving treatment decisions using personalized risk assessment from the International IgA Nephropathy Prediction Tool
Authors: Sean J. Barbour, Mark Canney, Rosanna Coppo, Hong Zhang, Zhi-Hong Liu, Yusuke Suzuki, Keiichi Matsuzaki, Ritsuko Katafuchi, Dilshani Induruwage, Lee Er, Heather N. Reich, John Feehally, Jonathan Barratt, Daniel C. Cattran, M.L. Russo, S. Troyanov, H.T. Cook, I. Roberts, V. Tesar, D. Maixnerova, S. Lundberg, L. Gesualdo, F. Emma, L. Fuiano, G. Beltrame, C. Rollino, A. Amore, R. Camilla, L. Peruzzi, M. Praga, S. Feriozzi, R. Polci, G. Segoloni, L. Colla, A. Pani, D. Piras, A. Angioi, G. Cancarini, S. Ravera, M. Durlik, E. Moggia, J. Ballarin, S. Di Giulio, F. Pugliese, I. Serriello, Y. Caliskan, M. Sever, I. Kilicaslan, F. Locatelli, L. Del Vecchio, J.F.M. Wetzels, H. Peters, U. Berg, F. Carvalho, A.C. da Costa Ferreira, M. Maggio, A. Wiecek, M. Ots-Rosenberg, R. Magistroni, R. Topaloglu, Y. Bilginer, M. D’Amico, M. Stangou, F. Giacchino, D. Goumenos, P. Kalliakmani, M. Gerolymos, K. Galesic, C. Geddes, K. Siamopoulos, O. Balafa, M. Galliani, P. Stratta, M. Quaglia, R. Bergia, R. Cravero, M. Salvadori, L. Cirami, B. Fellstrom, H. Kloster Smerud, F. Ferrario, T. Stellato, J. Egido, C. Martin, J. Floege, F. Eitner, A. Lupo, P. Bernich, P. Menè, M. Morosetti, C. van Kooten, T. Rabelink, M.E.J. Reinders, J.M. Boria Grinyo, S. Cusinato, L. Benozzi, S. Savoldi, C. Licata, M. Mizerska-Wasiak, G. Martina, A. Messuerotti, A. Dal Canton, C. Esposito, C. Migotto, G. Triolo, F. Mariano, C. Pozzi, R. Boero, S. Bellur, G. Mazzucco, C. Giannakakis, E. Honsova, B. Sundelin, A.M. Di Palma, F. Ferrario, E. Gutiérrez, A.M. Asunis, J. Barratt, R. Tardanico, A. Perkowska-Ptasinska, J. Arce Terroba, M. Fortunato, A. Pantzaki, Y. Ozluk, E. Steenbergen, M. Soderberg, Z. Riispere, L. Furci, D. Orhan, D. Kipgen, D. Casartelli, D. Galesic Ljubanovic, H. Gakiopoulou, E. Bertoni, P. Cannata Ortiz, H. Karkoszka, H.J. Groene, A. Stoppacciaro, I. Bajema, J. Bruijn, X. Fulladosa Oliveras, J. Maldyk, E. Ioachim, N. Bavbek, T. Cook, S. Troyanov, C. Alpers, A. Amore, J. Barratt, F. Berthoux, S. Bonsib, J. Bruijn, V. D’Agati, G. D’Amico, S. Emancipator, F. Emmal, F. Ferrario, F. Fervenza, S. Florquin, A. Fogo, C. Geddes, H. Groene, M. Haas, P. Hill, R. Hogg, S. Hsu, T. Hunley, M. Hladunewich, C. Jennette, K. Joh, B. Julian, T. Kawamura, F. Lai, C. Leung, L. Li, P. Li, Z. Liu, A. Massat, B. Mackinnon, S. Mezzano, F. Schena, Y. Tomino, P. Walker, H. Wang, J. Weening, N. Yoshikawa N, C.-H. Zeng, S. Shi, C. Nogi, H. Suzuki, K. Koike, K. Hirano, T. Kawamura, T. Yokoo, M. Hanai, K. Fukami, K. Takahashi, Y. Yuzawa, M. Niwa, Y. Yasuda, S. Maruyama, D. Ichikawa, T. Suzuki, S. Shirai, A. Fukuda, S. Fujimoto, H. Trimarchi
Journal: Kidney International (2020)
The Pulmonary Arterial Tree in Atrial Septal Defect
Authors: C. A. WAGENVOORT, HENRY N. NEUFELD, JAMES W. DUSHANE, JESSE E. EDWARDS, Noeke Wagenvoort
Journal: Circulation (1961)

The pulmonary vascular tree was studied in 12 cases of uncomplicated atrial septal defect in fetuses, infants, and children. The ages of these subjects ranged from 24 weeks of fetal life to 11 years. A quantitative analysis was made of the medial thickness and of the index of medial surface area (ratio of medial tissue to pulmonary parenchyma) of the pulmonary arterial branches. In contrast to subjects with ventricular septal defect in corresponding age groups, the three fetuses in this series had medial hypertrophy, as indicated by a high index of medial surface area. In the postnatal group, both the medial thickness and the index of medial surface area were also usually greater than in the controls of corresponding ages, notably in two patients, who, at the ages of 7 weeks and 4 months, died of cardiac failure. No satisfactory explanation for these unexpected findings can be offered. Slight to moderate intimal proliferation was observed in some muscular and elastic pulmonary arteries, in bronchial arteries, and in pulmonary veins in several subjects. Thickening of the intima in elastic arteries was observed in a fetus of 26 weeks' gestation. Pronounced obliterative intimal changes were found in only one subject, an 11-year-old girl with severe pulmonary hypertension.
Relative survival in early-stage cancers in the Netherlands: a population-based study
Authors: Avinash G. Dinmohamed, Valery E. P. P. Lemmens, Ignace H. J. T. de Hingh, Otto Visser
Journal: Journal of Hematology & Oncology (2020)

Abstract In this nationwide, population-based study, we assessed 10-year relative survival among 225,305 patients with ten early-stage cancers diagnosed in the Netherlands during 2004–2015. This study aimed to ascertain which early-stage cancer is associated with minimal or no excess mortality and likely to be diagnosed in individuals who are otherwise more healthy or health-conscious than their counterparts in the general population. Ten-year relative survival marginally exceeded 100% in patients with early-stage prostate cancer, while it was close to 100% for patients with ductal carcinoma in situ (DCIS) and stage I cancers of the breast, skin (melanoma), testis, and thyroid. In contrast, patients with early-stage oral/pharyngeal, bladder, lung, and pancreatic cancers experienced considerable excess mortality, reflected by a 10-year relative survival of 74.9%, 69.4%, 45.5%, and 33.9%, respectively. Collectively, the life expectancy of patients with DCIS and early-stage cancers of the prostate, breast, skin (melanoma), testis, and thyroid parallels the expected survival of an age-, sex-, and calendar year-matched group from the general population. Our study findings add to the controversy surrounding overdiagnosis of particular early-stage cancers that are generally not destined to metastasis or cause excess mortality.
Resistant Hypertension and Risk of Adverse Events in Individuals With Type 1 Diabetes: A Nationwide Prospective Study
Authors: Raija Lithovius, Valma Harjutsalo, Stefan Mutter, Daniel Gordin, Carol Forsblom, Per-Henrik Groop
Journal: Diabetes Care (2020)

OBJECTIVE To estimate the risk of diabetic nephropathy (DN) progression, incident coronary heart disease (CHD) and stroke, and all-cause mortality associated with resistant hypertension (RH) in individuals with type 1 diabetes stratified by stages of DN, renal function, and sex. RESEARCH DESIGN AND METHODS This prospective study included a nationally representative cohort of individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study who had purchases of antihypertensive drugs at (±6 months) baseline visit (1995–2008). Individuals (N = 1,103) were divided into three groups: 1) RH, 2) uncontrolled blood pressure (BP) but no RH, and 3) controlled BP. DN progression, cardiovascular events, and deaths were identified from the individuals’ health care records and national registries until 31 December 2015. RESULTS At baseline, 18.7% of the participants had RH, while 23.4% had controlled BP. After full adjustments for clinical confounders, RH was associated with increased risk of DN progression (hazard ratio 1.95 [95% CI 1.37, 2.79], P = 0.0002), while no differences were observed in those with no RH (1.05 [0.76, 1.44], P = 0.8) compared with those who had controlled BP. The risk of incident CHD, incident stroke, and all-cause mortality was higher in individuals with RH compared with those who had controlled BP but not beyond albuminuria and reduced kidney function. Notably, in those with normo- and microalbuminuria, the risk of stroke remained higher in the RH compared with the controlled BP group (3.49 [81.20, 10.15], P = 0.02). CONCLUSIONS Our findings highlight the importance of identifying and providing diagnostic and therapeutic counseling to these very-high-risk individuals with RH.
COVID-19 and the nicotinic cholinergic system
Authors: Konstantinos Farsalinos, Athina Angelopoulou, Nikos Alexandris, Konstantinos Poulas
Journal: European Respiratory Journal (2020)

<b>The prevalence of smoking among hospitalised COVID-19 patients is low. COVID-19 manifestations could be linked to impairment of the cholinergic anti-inflammatory pathway. Nicotinic cholinergic agonists should be examined as potential therapeutic options.</b>https://bit.ly/2zfUZ1S
Abstract 11953: Statin Use is Associated With Lower Mortality in Patients With Breast Cancer
Authors: Ohad Oren, Eric H Yang, Thorvardur R Halfdanarson, Karen M Fischer, Diane E Grill, Stephen L Kopecky
Journal: Circulation (2019)

Introduction: Patients with invasive breast cancer (IBC) are exposed to a variety of cardio-toxic treatments. Hypothesis: The use of statin medications in patients with IBC is associated with bette...
Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study
Authors: Christopher M Petrilli, Simon A Jones, Jie Yang, Harish Rajagopalan, Luke O’Donnell, Yelena Chernyak, Katie A Tobin, Robert J Cerfolio, Fritz Francois, Leora I Horwitz
Journal: BMJ (2020)

<h3>Abstract</h3> <h3>Objective</h3> To describe outcomes of people admitted to hospital with coronavirus disease 2019 (covid-19) in the United States, and the clinical and laboratory characteristics associated with severity of illness. <h3>Design</h3> Prospective cohort study. <h3>Setting</h3> Single academic medical center in New York City and Long Island. <h3>Participants</h3> 5279 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection between 1 March 2020 and 8 April 2020. The final date of follow up was 5 May 2020. <h3>Main outcome measures</h3> Outcomes were admission to hospital, critical illness (intensive care, mechanical ventilation, discharge to hospice care, or death), and discharge to hospice care or death. Predictors included patient characteristics, medical history, vital signs, and laboratory results. Multivariable logistic regression was conducted to identify risk factors for adverse outcomes, and competing risk survival analysis for mortality. <h3>Results</h3> Of 11 544 people tested for SARS-Cov-2, 5566 (48.2%) were positive. After exclusions, 5279 were included. 2741 of these 5279 (51.9%) were admitted to hospital, of whom 1904 (69.5%) were discharged alive without hospice care and 665 (24.3%) were discharged to hospice care or died. Of 647 (23.6%) patients requiring mechanical ventilation, 391 (60.4%) died and 170 (26.2%) were extubated or discharged. The strongest risk for hospital admission was associated with age, with an odds ratio of &gt;2 for all age groups older than 44 years and 37.9 (95% confidence interval 26.1 to 56.0) for ages 75 years and older. Other risks were heart failure (4.4, 2.6 to 8.0), male sex (2.8, 2.4 to 3.2), chronic kidney disease (2.6, 1.9 to 3.6), and any increase in body mass index (BMI) (eg, for BMI &gt;40: 2.5, 1.8 to 3.4). The strongest risks for critical illness besides age were associated with heart failure (1.9, 1.4 to 2.5), BMI &gt;40 (1.5, 1.0 to 2.2), and male sex (1.5, 1.3 to 1.8). Admission oxygen saturation of &lt;88% (3.7, 2.8 to 4.8), troponin level &gt;1 (4.8, 2.1 to 10.9), C reactive protein level &gt;200 (5.1, 2.8 to 9.2), and D-dimer level &gt;2500 (3.9, 2.6 to 6.0) were, however, more strongly associated with critical illness than age or comorbidities. Risk of critical illness decreased significantly over the study period. Similar associations were found for mortality alone. <h3>Conclusions</h3> Age and comorbidities were found to be strong predictors of hospital admission and to a lesser extent of critical illness and mortality in people with covid-19; however, impairment of oxygen on admission and markers of inflammation were most strongly associated with critical illness and mortality. Outcomes seem to be improving over time, potentially suggesting improvements in care.
Medicare funding of nurse education. The case for policy change
Authors: L H Aiken, M E Gwyther
Journal: JAMA (1995)

To determine the magnitude and distribution of US Medicare funding for nursing education and to assess the extent to which Medicare funding contributes to meeting national health care workforce priorities.Medicare Hospital Cost Report Information System, American Hospital Association Annual Survey of Hospitals, and National League for Nursing national surveys of schools of nursing.Using hospital identifiers, data from three data sets were merged and analyzed to estimate percentage distributions of Medicare funding according to types of educational programs, hospital characteristics, and student enrollment.Fifteen percent of direct Medicare graduate medical education funding goes to hospitals for the training of nurses and paramedical personnel. Totaling approximately $174 million in 1991, 71% of these funds went to hospitals for nursing education costs. Most of the nation's teaching hospitals (289 of 381 Council of Teaching Hospitals member hospitals) and nurse education programs (1112 of 1484) do not qualify under existing policies for Medicare nursing education reimbursement. Sixty-six percent of Medicare nurse training funds, totaling $114 million in 1991, went to 145 hospitals operating diploma nursing programs; these programs produce less than 10% of nurse graduates. Three states (Pennsylvania, New Jersey, and Ohio) received nearly one half (48%) of the $114 million for diploma nursing education.Medicare is the largest single source of federal support for nursing education. Yet, the majority of Medicare nursing education funding goes to hospitals affiliated with an increasingly smaller, idiosyncratic subset of nurse training programs. Unlike graduate medical education, Medicare supports primarily preprofessional education in nursing. Graduate education, including the preparation of nurse practitioners, does not generally qualify for reimbursement. Medicare reimbursement for nursing education must be retargeted.