tbuckley/cabot-search huggingface dataset:
Certifying the interruption of wild poliovirus transmission in the WHO African region on the turbulent journey to a polio-free world
Authors: Rose Gana Fomban Leke, Arlene King, Mark A Pallansch, Rudolf H Tangermann, Pascal Mkanda, Supamit Chunsuttiwat, Abdoulie Jack, B Jean Kaboré, Ibrahima Kane, Ngokoana Esther Khomo, Raul Jorge Lopes-Feio, Zakaria Mahamadine Maiga, William Bahati Pungu Matuja, Naddumba Edward Kironde, Beugré Kouassi, Bijan Sadrizadeh, Oyewale Tomori
Journal: The Lancet Global Health (2020)

<h2>Summary</h2> On Aug 25 2020, the Africa Regional Commission for the Certification of Poliomyelitis Eradication declared that the WHO African region had interrupted transmission of all indigenous wild polioviruses. This declaration marks the African region as the fifth of the six WHO regions to celebrate this extraordinary achievement. Following the Yaoundé Declaration on Polio Eradication in Africa by heads of state and governments in 1996, Nelson Mandela launched the <i>Kick Polio out of Africa</i> campaign. In this Health Policy paper, we describe the long and turbulent journey to the certification of the interruption of wild poliovirus transmission, focusing on 2016–20, lessons learned, and the strategies and analyses that convinced the Regional Commission that the African region is free of wild polioviruses. This certification of the WHO African region shows the feasibility of polio eradication in countries with chronic insecurity, inaccessible and hard-to-reach populations, and weak health systems. Challenges have been daunting and the sacrifices enormous—dozens of health workers and volunteers have lost their lives in the pursuit of a polio-free Africa.
Immune Stimulation With Recombinant Human Granulocyte Colony–Stimulating Factor for Coronavirus Disease 2019 (COVID-19)—Beware of Blind Spots
Authors: Nuala J. Meyer, Robert B. Lindell, E. John Wherry
Journal: JAMA Internal Medicine (2020)

Effect of Recombinant Human Granulocyte Colony–Stimulating Factor for Patients With COVID-19 and Lymphopenia
Challenges Facing Family Practice and Primary Care—Reply
Authors: Robert Graham, Richard G. Roberts, Daniel J. Ostergaard, Norman B. Kahn, Perry A. Pugno, Larry A. Green
Journal: JAMA (2003)

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
Sphingosine kinase 2 restricts T cell immunopathology but permits viral persistence
Authors: Caleb J. Studstill, Curtis J. Pritzl, Young-Jin Seo, Dae Young Kim, Chuan Xia, Jennifer J. Wolf, Ravi Nistala, Madhuvanthi Vijayan, Yong-Bin Cho, Kyung Won Kang, Sang-Myeong Lee, Bumsuk Hahm
Journal: Journal of Clinical Investigation (2020)

Chronic viral infections are often established by the exploitation of immune-regulatory mechanisms that result in nonfunctional T cell responses. Viruses that establish persistent infections remain a serious threat to human health. Sphingosine kinase 2 (SphK2) generates sphingosine 1-phosphate, which is a molecule known to regulate multiple cellular processes. However, little is known about SphK2's role during the host immune responses to viral infection. Here, we demonstrate that SphK2 functions during lymphocytic choriomeningitis virus Cl 13 (LCMV Cl 13) infection to limit T cell immune pathology, which subsequently aids in the establishment of virus-induced immunosuppression and the resultant viral persistence. The infection of Sphk2-deficient (Sphk2-/-) mice with LCMV Cl 13 led to the development of nephropathy and mortality via T cell-mediated immunopathology. Following LCMV infection, Sphk2-/- CD4+ T cells displayed increased activity and proliferation, and these cells promoted overactive LCMV Cl 13-specific CD8+ T cell responses. Notably, oral instillation of an SphK2-selective inhibitor promoted protective T cell responses and accelerated the termination of LCMV Cl 13 persistence in mice. Thus, SphK2 is indicated as an immunotherapeutic target for the control of persistent viral infections.
Mineral bone disease in autosomal dominant polycystic kidney disease
Authors: Berenice Gitomer, Renata Pereira, Isidro B. Salusky, Jason W. Stoneback, Tamara Isakova, Xuan Cai, Lorien S. Dalrymple, Norma Ofsthun, Zhiying You, Harmut H. Malluche, Franklin Maddux, Diana George, Vicente Torres, Arlene Chapman, Theodore I. Steinman, Myles Wolf, Michel Chonchol
Journal: Kidney International (2020)
Gene-drug interactions for NSAID use in preventing colorectal neoplasia: a review
Authors: James Cross, Elizabeth Poole, Cornelia Ulrich
Journal: Cancer Research (2007)

5588  Background: Non-steroidal antiinflammatory drugs (NSAIDs) have been identified as effective chemopreventive agents for colorectal neoplasia. However, use of these agents is limited by the potential for adverse reactions, including gastrointestinal and cardiovascular toxicity. NSAIDs primarily target the cyclooxygenase (COX) enzymes in prostaglandin synthesis. Polymorphisms in COX1, COX2, or enzymes relevant to NSAID pharmacodynamics may affect NSAID efficacy or toxicity. We conducted a review of the literature to summarize current evidence of potential gene-drug interactions between NSAID use and polymorphisms in COX1 and COX2. We also reviewed the literature for an interaction between NSAID exposure and ornithine decarboxylase (ODC), because NSAIDs promote polyamine catabolism in colon cancer. Methods: We searched OVID and PubMed databases for publications reporting interactions between NSAID use and COX1, COX2, or ODC polymorphisms and risk of colorectal neoplasia. We reviewed all articles containing at least one keyword from each of four search sets: (1) NSAID, antiinflammatory, nonsteroidal, aspirin, or acetylsalicylic, and (2) polymorphism, variant, or mutation, and (3) colon, rectum, rectal, colorectal, or colonic and (4) cancer, adenoma, polyp, or neoplasia. Results: Of 335 corresponding search results, ten reported an interaction. One study reported a significant interaction between NSAID use and the COX1 P17L polymorphism (P = 0.03) whereby the risk reduction associated with NSAID use among homozygous wildtype genotypes was not observed among NSAID users with variant alleles. Another study showed that the ODC 315G>A polymorphism significantly modified the effect of NSAID use (P = 0.02) whereby NSAIDs reduced adenoma risk only among those with variant alleles. No statistically significant interactions have been reported for polymorphisms in COX2. An interaction with COX2 -765G>C approached significance (P = 0.07) in one study, whereby the risk reduction associated with NSAID use was greater among homozygous variant individuals than among those with heterozygous or homozygous wildtype genotypes. Nonsignificant interactions were reported for COX1, COX2, and ODC gene polymorphisms among seven remaining studies, ranging in size from 161 to 726 cases and from 219 to 729 controls. Conclusion: The literature on NSAID-gene interactions to date is limited. Recent pharmacodynamic data support the potential for gene-drug interactions for COX1 P17L. Although most studies reported statistically nonsignificant interactions, reliable detection will require greater sample sizes and evaluation of clinical trial subjects of chemoprevention studies. We are continuing to review further polymorphisms in prostaglandin-mediated inflammation for potential effect modification and will incorporate this information in the abstract presentation.
Associations Between Depressive Symptoms and HFpEF-Related Outcomes
Authors: Alvin Chandra, Michael A.D. Alcala, Brian Claggett, Akshay S. Desai, James C. Fang, John F. Heitner, Jiankang Liu, Bertram Pitt, Scott D. Solomon, Marc A. Pfeffer, Eldrin F. Lewis
Journal: JACC Heart Failure (2020)
Palliative Care in Parkinson Disease—Is It Beneficial for All?—Reply
Authors: Benzi M. Kluger, Steven Pantilat, Janis Miyasaki
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Assessment of biorisk management systems in high containment laboratories, 18 countries in Europe, 2016 and 2017
Authors: Sandra Appelt, Daniela Jacob, Anna-Maria Rohleder, Andreas Bråve, Åsa Szekely Björndal, Antonino Di Caro, Roland Grunow
Journal: Eurosurveillance (2020)

Europe-wide activities to improve biosafety and biosecurity performed within the frameworks of the European Union (EU)-funded Joint Actions EMERGE and QUANDHIP led to the development of an Integrated European Checklist for Laboratory Biorisk Management (ECL).To better understand different approaches shaping biorisk management (BRM) systems on an operational level in high containment laboratories, the ECL was used to map the implementation of BRM in 32 high containment laboratories in 18 countries in Europe. The results suggest that the BRM elements referring to standard microbiological working practices and the handling of infectious material were fulfilled particularly well. The elements safety exercises involving internal and external emergency responders, and appropriate decommissioning plans were not fulfilled particularly well. BRM in Biosafety Level (BSL) 4 laboratories handling Risk Group (RG) 4 viruses appear to vary among each other less than BSL3 laboratories handling RG 3 bacteria. It is important to agree on comparable regulations in Europe as high containment laboratories are indispensable for a safe, quick and effective response to public health threats. As high containment laboratories may also present a public health risk it is crucial to have robust BRM on organisational and operational levels.
Effect of Androgen Deprivation on Long-term Outcomes of Intermediate-Risk Prostate Cancer Stratified as Favorable or Unfavorable
Authors: Zachary S. Zumsteg, Daniel E. Spratt, Timothy J. Daskivich, Mourad Tighiouart, Michael Luu, Joseph P. Rodgers, Howard M. Sandler
Journal: JAMA Network Open (2020)

This secondary analysis of a randomized clinical trial examines the effect of androgen deprivation therapy (ADT) during radiotherapy in patients who were classified as having either favorable intermediate-risk or unfavorable intermediate-risk prostate cancer.
AB0864 DO CORTICOSTEROIDS AND HYALURONIC ACID INJECTIONS CAUSE INFECTIONS? A SYSTEMATIC REVIEW OF LITERATURE ON ADVERSE EFFECTS AND INFECTION RATES OF INTRA-ARTICULAR CORTICOSTEROID AND HYALURONIC ACID INJECTIONS IN PATIENTS WITH KNEE OSTEOARTHRITIS
Authors: C. Hatzantonis
Journal: Annals of the Rheumatic Diseases (2020)

Background: Knee osteoarthritis has been a leading cause of chronic pain and disability in our increasingly aging population. Conservative management options of physiotherapy and oral analgesics offer some relief, but delivery of intra-articular injections such as corticosteroids or hyaluronic acid has increasingly become the mainstay of pain management of knee osteoarthritis. In a clinical setting, intra-articular injections offer a means to delay a total knee replacement. Despite the abundance of literature on corticosteroids and hyaluronic acid, there is no known percentage of infection rates or adverse effects that clinicians may use to inform patients prior to obtaining consent for the injection. Objectives: To determine a rate of adverse events and infection rates in patients undergoing intra-articular injections of corticosteroids or hyaluronic acid. Methods: A systematic review of current literature including studies involving patients ranging from 45 patients (Carmona L, 2018) to Cochrane reviews of 1767 patients (Campbell Kirk, 2015). From these studies, the number of patients, adverse reactions (i.e. pain, erythema) and serious adverse reactions (infections) were calculated. Results: Within our study, there was a large variation of numbers of adverse effects of hyaluronic acid and corticosteroids amongst studies, with percentages as variable as 0-9.3%. Corticosteroids demonstrated 11-26% reduction of adverse events compared to hyaluronic acid. However, confidence intervals were found to not be statistically significant. Conclusion: Intra-articular injections of corticosteroids and hyaluronic acid, although deemed clinically effective, continue to demonstrate variable rates of adverse effects and infection amongst patients with progressive knee osteoarthritis. Disclosure of Interests: None declared
Risk factors associated with bleeding after prophylactic endoscopic variceal ligation in cirrhosis
Authors: Andreas Drolz, Christoph Schramm, Oliver Seiz, Stefan Groth, Eik Vettorazzi, Thomas Horvatits, Malte H. Wehmeyer, Christoph Schramm, Tobias Goeser, Thomas Roesch, Ansgar W. Lohse, Johannes Kluwe
Journal: Endoscopy (2020)

Background Prophylactic endoscopic variceal band ligation (EVL) is frequently performed in patients with liver cirrhosis. The aim of our study was to identify factors associated with early upper gastrointestinal bleeding (UGIB) in cirrhosis patients after prophylactic EVL. Methods 787 nonemergency EVLs performed in 444 patients in two German University medical centers were analyzed retrospectively. Results Within 30 days after EVL, 38 UGIBs were observed (4.8 % of all procedures). Bilirubin levels (hazard ratio [HR] 1.5, 95 % confidence interval [CI] 1.2–2.0 for a 2-fold increase) and presence of varices grade III/IV according to Paquet (HR 2.6, 95 %CI 1.3–5.0 compared with absence or smaller sized varices) were independently associated with UGIB following EVL. International normalized ratio (INR) was associated with bleeding events in the univariate analysis but did not reach statistical significance after adjustment for bilirubin and presence of varices grade III/IV (HR 1.2, 95 %CI 0.9–1.6 for an increase by 0.25). There was no statistically significant association between platelet count or fibrinogen levels and UGIB. Substitution of coagulation products did not affect incidence of bleeding after EVL, which also applied to patients with “coagulopathy” (INR &gt; 1.5 and/or platelet count &lt; 50 × 109/L). No association between proton pump inhibitor therapy and post-EVL UGIB was observed. Conclusions EVL is a safe procedure and immediate bleeding complications are rare. Serum bilirubin levels and size of varices, rather than coagulation indices, are associated with UGIB after EVL. Our data do not support the preventive substitution of blood or coagulation products.
Caring for patients in a new pandemic: the necessity and challenges of observational research
Authors: David L. Thomas
Journal: Journal of Clinical Investigation (2020)

Individuals with coronavirus disease 2019 (COVID-19) can develop pneumonia and a severe inflammatory response with excessive cytokine release known as the cytokine storm. The JAK inhibitor baricitinib, used to treat rheumatoid arthritis, reduces inflammation by modifying the cytokine pathway. In this issue of the JCI, Bronte, Ugel, and colleagues performed an observational longitudinal study to evaluate the use of baricitinib in 20 patients with COVID-19. The treated patients showed reduced levels of plasma IL-6, TNF, IL-1β, and phosphorylated STAT3 as well as swift lymphocyte restoration. Notably, these patients had a dramatically favorable clinical outcome. While bias can plague uncontrolled research, this study has biological credibility and warrants randomized, controlled studies.
YY1 deficiency in β-cells leads to mitochondrial dysfunction and diabetes in mice
Authors: Dalong Song, Qi Yang, Xiuli Jiang, Aijing Shan, Jingminjie Nan, Ying Lei, He Ji, Wei Di, Tianxiao Yang, Tiange Wang, Weiqing Wang, Guang Ning, Yanan Cao
Journal: Metabolism (2020)
Response to: ‘Tofacitinib for the treatment of polyarteritis nodosa: a literature review’. Correspondence on ‘Tofacitinib for polyarteritis nodosa: a tailored therapy’ by Rimar<i>et al</i>
Authors: Doron Rimar, Abid Awisat, Lisa Kaly, Gleb Slobodin, Itzhak Rosner, Michael Rozenbaum, Shira Ginsberg, Elina Starosvetsky, Ayelet Alpert, Shai Shen-Orr
Journal: Annals of the Rheumatic Diseases (2020)

We appreciate the interest of Akiyama et al in our report and thank them for the data presented in their letter. 1 2Akiyama et al have presented a thorough literature review and have described a positive and efficacious effect of tocilizumab in 11 cases of refractory polyarteritis nodosa (PAN) described in 6 case series.Indeed, the use of tocilizumab, an interleukin (IL)-6 inhibitor, in vasculitis is gaining evidence in the literature, specifically in large vessel vasculitis including giant cell arteritis and Takayasu arteritis. 3 4Nevertheless, it should be noted that although the IL-6 pathway is the major inducer of STAT 3, and therefore was used by us in vitro to stimulate this pathway in order to evaluate STAT 3 activation, clinically blocking the IL-6 pathway in our patient, using tocilizumab, was not beneficial, contrasting with our positive result with tofacitinib.We hypothesised that redundancy or other stimulators of the STAT 3 pathway like IL-23 may explain this discrepancy.Furthermore, we did not find tocilizumab clinically or radiologically beneficial in another patient with severe refractory PAN involving skin and coronary arteries-evidenced by positron emission tomography-CT scan revealing active inflammation in an aneurism within a coronary artery and by MRI demonstrating active deep skin involvement while under treatment with tocilizumab (unpublished data).Thus, in considering the review by Akiyama et al, publication bias should always be considered when evaluating case reports, as we all tend to prefer publishing our positive experience.Recently, we have also reported our positive experience with another agent, infliximab, for refractory PAN and reviewed the literature. 5The ever-expanding spectrum of biological treatments is confusing for the practitioner and although case reports and case series are important to guide us in rare refractory patients, we should still follow guidelines and use evidence-based treatments that were evaluated in large randomised controlled clinical trials as first-line therapy.New technologies may help us diagnose and treat refractory patients.Whole-exome sequencing studies may reveal novel mimickers, the monogenic vasculitides, as deficiency of adenosine deaminase 2, stimulator of interferon genes-associated vasculopathy with onset in infancy, and haploinsufficiency of A20 that should be considered in refractory cases.Finally, precision medicine, as we suggested in our report, may guide us in the future, helping us to find the right fit for each patient.
Association of Miglustat With Swallowing Outcomes in Niemann-Pick Disease, Type C1
Authors: Beth I. Solomon, Andrew C. Smith, Ninet Sinaii, Nicole Farhat, Monique C. King, Leonza Machielse, Forbes D. Porter
Journal: JAMA Neurology (2020)

Niemann-Pick disease, type C1 (NPC1) is a progressive neurovisceral disease with no US Food and Drug Administration-approved therapy. Miglustat, a drug used off-label in the United States for the treatment of NPC1, appears to stabilize neurologic disease progression. Several prospective trials suggest that miglustat stabilizes oropharyngeal swallowing function; however, its effect on dysphagia and aspiration risk has not been demonstrated instrumentally.To determine if miglustat therapy is associated with stabilized swallowing dysfunction in individuals with NPC1.Patients with confirmed NPC1 diagnoses were evaluated in a single-center cohort study of NPC1 from April 1997 to November 2019. Longitudinal data from individuals with neurologic disease onset prior to age 15 years were analyzed. The study population was divided into those with neurologic disease onset in early childhood (age <6 years) and late childhood (age ≥6 years and <15 years). Analysis began September 2019.Oral miglustat at baseline and at follow-up.Oropharyngeal swallowing function was assessed with videofluoroscopic swallowing studies. Overall swallowing ability and aspiration risk were evaluated using the American Speech-Language-Hearing Association National Outcome Measurement System swallowing domain and an adapted Rosenbek aspiration-penetration scale, respectively.Overall, 50 participants were evaluated at baseline (median [interquartile range] age, 9.4 [3.4-16.4] years; 26 [52%] female). The median (interquartile range) duration of follow-up was 3.0 (1.1-4.4) years. Miglustat use was associated with decreased odds of worse American Speech-Language-Hearing Association National Outcome Measurement System swallowing domain outcomes in all 3 subsets (overall: odds ratio [OR], 0.09 [95% CI, 0.02-0.36); P < .001; early childhood: OR, 0.17 [95% CI, 0.04-0.67]; P = .01; late childhood: OR, 0.05 [95% CI, 0.01-0.29]; P = .001). Miglustat use was associated with decreased odds of worse Rosenbek aspiration-penetration scale outcomes in the overall cohort (OR, 0.28 [95% CI, 0.08-0.95]; P = .04) but not in each subgroup (early childhood: OR, 0.27 [95% CI, 0.06-1.22]; P = .09; late childhood: OR, 0.38 [95% CI, 0.06-2.33]; P = .29).These data suggest that miglustat use is associated with stabilized swallowing function and reduced aspiration risk in NPC1, thus supporting its use in this population. In addition, these data demonstrate that a quantification of swallowing dysfunction can be used as a clinically relevant, functional outcome measure in future therapeutic trials in NPC1.