tbuckley/cabot-search huggingface dataset:
Response to: ‘Comparative analysis of synovial inflammation after SARS-CoV-2 infection' by Alivernini et al
Authors: María-del-Carmen López-González, Vega Jovani, Esperanza Merino, Paloma Vela, Mariano Andrés
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Objective</h3> Recent evidence supports the use of normal saline flushes in place of heparin to maintain the patency of peripheral intravenous locks (IVLs); however, there are no data regarding the recommended flush frequency. <h3>Study design</h3> This was an open, non-inferiority, randomised controlled trial. Children with IVLs, aged 1–17 years, were randomly assigned to receive saline flushing every 12 h (group A) or every 24 h (group B). The main outcome was the maintenance of catheter patency. <h3>Results</h3> Four hundred patients were randomised; 198 subjects were analysed in the 12 h group and 199 in the 24 h group (three patients were lost at follow-up). Occlusion occurred in 15 children (7.6%) in group A versus 9 (4.5%) in group B (p=0.21). The difference in catheter patency was +3.1% in favour of the 24 h group (95% CI −1.6% to 7.7%), showing the non-inferiority of the 24 h procedure (the non-inferiority margin was set at −4%). Catheter-related complications were not different between the two groups (12.1% in group A vs 9.5% in group B; p=0.42). <h3>Conclusions</h3> A flushing procedure with one flush per day allows maintenance of catheter patency without an increase in catheter-related complications. We propose a simplification of the flushing procedure with only one flush per day, thereby reducing costs (materials use and nursing time), labour and unnecessary manipulation of the catheters which can cause distress in younger children and their parents. <h3>Trial registration number</h3> The study is registered in the international database ClinicalTrial.gov under registration number NCT02221024.
High-resolution temporal profiling of the human gut microbiome reveals consistent and cascading alterations in response to dietary glycans
Authors: Richard Creswell, Jie Tan, Jonathan W. Leff, Brandon Brooks, Michael A. Mahowald, Ruth Thieroff-Ekerdt, Georg K. Gerber
Journal: Genome Medicine (2020)

Abstract Background Dietary glycans, widely used as food ingredients and not directly digested by humans, are of intense interest for their beneficial roles in human health through shaping the microbiome. Characterizing the consistency and temporal responses of the gut microbiome to glycans is critical for rationally developing and deploying these compounds as therapeutics. Methods We investigated the effect of two chemically distinct glycans (fructooligosaccharides and polydextrose) through three clinical studies conducted with 80 healthy volunteers. Stool samples, collected at dense temporal resolution (~ 4 times per week over 10 weeks) and analyzed using shotgun metagenomic sequencing, enabled detailed characterization of participants’ microbiomes. For analyzing the microbiome time-series data, we developed MC-TIMME2 (Microbial Counts Trajectories Infinite Mixture Model Engine 2.0), a purpose-built computational tool based on nonparametric Bayesian methods that infer temporal patterns induced by perturbations and groups of microbes sharing these patterns. Results Overall microbiome structure as well as individual taxa showed rapid, consistent, and durable alterations across participants, regardless of compound dose or the order in which glycans were consumed. Significant changes also occurred in the abundances of microbial carbohydrate utilization genes in response to polydextrose, but not in response to fructooligosaccharides. Using MC-TIMME2, we produced detailed, high-resolution temporal maps of the microbiota in response to glycans within and across microbiomes. Conclusions Our findings indicate that dietary glycans cause reproducible, dynamic, and differential alterations to the community structure of the human microbiome.
Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma‐Associated Interstitial Lung Disease
Authors: Changwan Ryu, Anjali Walia, Vivian Ortiz, Carrighan Perry, Sam Woo, Benjamin C. Reeves, Huanxing Sun, Julia Winkler, Jean E. Kanyo, Weiwei Wang, Milica Vukmirovic, Nicholas Ristic, Eric A. Stratton, Sita Ram Meena, Maksym Minasyan, Daniel Kurbanov, Xinran Liu, TuKiet T. Lam, Giuseppina Farina, Jose L. Gomez, Mridu Gulati, Erica L. Herzog
Journal: Arthritis & Rheumatology (2020)

Objective Systemic sclerosis–associated interstitial lung disease (SSc‐ILD) is characterized by variable clinical outcomes, activation of innate immune pattern‐recognition receptors (PRRs), and accumulation of α‐smooth muscle actin (α‐SMA)–expressing myofibroblasts. The aim of this study was to identify an association between these entities and mitochondrial DNA (mtDNA), an endogenous ligand for the intracellular DNA–sensing PRRs Toll‐like receptor 9 (TLR‐9) and cyclic GMP‐AMP synthase/stimulator of interferon genes (cGAS/STING), which has yet to be determined. Methods Human lung fibroblasts (HLFs) from normal donors and SSc‐ILD explants were treated with synthetic CpG DNA and assayed for α‐SMA expression and extracellular mtDNA using quantitative polymerase chain reaction for the human MT‐ATP6 gene. Plasma MT‐ATP6 concentrations were evaluated in 2 independent SSc‐ILD cohorts and demographically matched controls. The ability of SSc‐ILD and control plasma to induce TLR‐9 and cGAS/STING activation was evaluated with commercially available HEK 293 reporter cells. Plasma concentrations of type I interferons (IFNs), interleukin‐6 (IL‐6), and oxidized DNA were measured using electrochemiluminescence and enzyme‐linked immunosorbent assay–based methods. Extracellular vesicles (EVs) precipitated from plasma were evaluated for MT‐ATP6 concentrations and proteomics via liquid chromatography mass spectrometry. Results Normal HLFs and SSc‐ILD fibroblasts developed increased α‐SMA expression and MT‐ATP6 release following CpG stimulation. Plasma mtDNA concentrations were increased in the 2 SSc‐ILD cohorts, reflective of ventilatory decline, and were positively associated with both TLR‐9 and cGAS/STING activation as well as type I IFN and IL‐6 expression. Plasma mtDNA was not oxidized and was conveyed by EVs displaying a proteomics profile consistent with a multicellular origin. Conclusion These findings demonstrate a previously unrecognized connection between EV‐encapsulated mtDNA, clinical outcomes, and intracellular DNA–sensing PRR activation in SSc‐ILD. Further study of these interactions could catalyze novel mechanistic and therapeutic insights into SSc‐ILD and related disorders.
Association of Nonsteroidal Anti-inflammatory Drug Use and Adverse Outcomes Among Patients Hospitalized With Influenza
Authors: Lars Christian Lund, Mette Reilev, Jesper Hallas, Kasper Bruun Kristensen, Reimar Wernich Thomsen, Christian Fynbo Christiansen, Henrik Toft Sørensen, Nanna Borup Johansen, Nikolai Constantin Brun, Marianne Voldstedlund, Henrik Støvring, Marianne Kragh Thomsen, Steffen Christensen, Anton Pottegård
Journal: JAMA Network Open (2020)

<h3>Importance</h3> During the ongoing coronavirus disease 2019 pandemic, case reports have suggested that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes. <h3>Objective</h3> To study the association of NSAID use with adverse outcomes in patients hospitalized with influenza or influenza pneumonia. <h3>Design, Setting, and Participants</h3> This cohort study used propensity score matching among 7747 individuals aged 40 years or older who were hospitalized with influenza, confirmed by polymerase chain reaction or antigen testing, between 2010 and 2018. Data were collected using Danish nationwide registers. All analyses reported were performed on May 29, 2020. <h3>Exposures</h3> Prescription fill of an NSAID within 60 days before admission. <h3>Main Outcomes and Measures</h3> Risk ratio (RR) and risk difference (RD) with 95% CIs for intensive care unit admission and death within 30 days of admission. <h3>Results</h3> A total of 7747 patients (median [interquartile range] age, 71 [59-80] years, 3980 [51.4%] men) with confirmed influenza were identified. Of these, 520 (6.7%) were exposed to NSAIDs. In the unmatched cohorts, 104 of 520 patients (20.0%) who used NSAIDs and 958 of 7227 patients (13.3%) who did not use NSAIDs were admitted to the intensive care unit. For death within 30 days of admission, we observed 37 events (7.1%) among those who used NSAIDs compared with 563 events (7.8%) among those who did not. Current NSAID use was associated with intensive care unit admission (RR, 1.51; 95% CI, 1.26 to 1.81; RD, 6.7%; 95% CI, 3.2% to 10.3%), while NSAID use was not associated with death (RR, 0.91; 95% CI, 0.66 to 1.26; RD, –0.7%; 95% CI, –3.0% to 1.6%). In the matched cohorts, risks were unchanged for patients who used NSAIDs, while 83 ICU admissions (16.0%) and 36 deaths (6.9%) were observed among matched individuals who did not use NSAIDs. Matched (ie, adjusted) analyses yielded attenuated risk estimates for intensive care unit admission (RR, 1.25; 95% CI, 0.95 to 1.63; RD, 4.0%; 95% CI, –0.6% to 8.7%) and death (RR, 1.03; 95% CI, 0.66 to 1.60; RD, 0.2%; 95% CI, –2.9% to 3.3%). Associations were more pronounced among patients who used NSAIDs for a longer period (eg, for intensive care unit admission: RR, 1.90; 95% CI, 1.19 to 3.06; RD, 13.4%; 95% CI, 4.0% to 22.8%). <h3>Conclusions and Relevance</h3> In this cohort study of adult patients hospitalized with influenza, the use of NSAIDs was not associated with 30-day intensive care unit admission or death in adjusted analyses. There was an association between long-term use of NSAIDs and intensive care unit admission.
NF1 optic pathway glioma: analyzing risk factors for visual outcome and indications to treat
Authors: Amedeo A Azizi, David A Walker, Jo-Fen Liu, Astrid Sehested, Timothy Jaspan, Berthold Pemp, Ian Simmons, Rosalie Ferner, Jacques Grill, Darren Hargrave, Pablo Hernáiz Driever, D Gareth Evans, Enrico Opocher
Journal: Neuro-Oncology (2020)

The aim of the project was to identify risk factors associated with visual progression and treatment indications in pediatric patients with neurofibromatosis type 1 associated optic pathway glioma (NF1-OPG).A multidisciplinary expert group consisting of ophthalmologists, pediatric neuro-oncologists, neurofibromatosis specialists, and neuro-radiologists involved in therapy trials assembled a cohort of children with NF1-OPG from 6 European countries with complete clinical, imaging, and visual outcome datasets. Using methods developed during a consensus workshop, visual and imaging data were reviewed by the expert team and analyzed to identify associations between factors at diagnosis with visual and imaging outcomes.Eighty-three patients (37 males, 46 females, mean age 5.1 ± 2.6 y; 1-13.1 y) registered in the European treatment trial SIOP LGG-2004 (recruited 2004-2012) were included. They were either observed or treated (at diagnosis/after follow-up).In multivariable analysis, factors present at diagnosis associated with adverse visual outcomes included: multiple visual signs and symptoms (adjusted odds ratio [adjOR]: 8.33; 95% CI: 1.9-36.45), abnormal visual behavior (adjOR: 4.15; 95% CI: 1.20-14.34), new onset of visual symptoms (adjOR: 4.04; 95% CI: 1.26-12.95), and optic atrophy (adjOR: 3.73; 95% CI: 1.13-12.53). Squint, posterior visual pathway tumor involvement, and bilateral pathway tumor involvement showed borderline significance. Treatment appeared to reduce tumor size but improved vision in only 10/45 treated patients. Children with visual deterioration after primary observation are more likely to improve with treatment than children treated at diagnosis.The analysis identified the importance of symptomatology, optic atrophy, and history of vision loss as predictive factors for poor visual outcomes in children with NF1-OPG.
An Apparition in Vilnius
Authors: Jack Coulehan
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
Abstract A74: The HIV protease inhibitor nelfinavir, alone or in combination with the proteasome inhibitor bortezomib, is cytotoxic to high-grade serous ovarian cancer cells regardless of platinum sensitivity
Authors: Mahbuba R. Subeha, Alicia A. Goyeneche, Michael A. Lisio, Carlos M. Telleria
Journal: Clinical Cancer Research (2020)

Abstract High-grade serous ovarian cancer (HGSOC) is a deadly disease, affecting women worldwide. Major challenges in treating HGSOC patients involve overcoming resistance to platinum (Pt)-based therapy by developing novel treatment approaches. Nelfinavir (NFV), an anti-HIV drug, has shown to be effective against cancers of high secretory capacity—e.g., multiple myeloma—by aggravating the stress of the endoplasmic reticulum (ER). Its potential therapeutic role against HGSOC, however, remains unclear. We hypothesized that simultaneous ER stress aggravation by NFV and blockage of the proteolytic capacity of the proteasome with a proteasome inhibitor should cause sufficient ER stress to tilt cells to a death fate. In this study, we investigated the cytotoxicity of the ER aggravator NFV as monotherapy and in combination with the proteasome inhibitor bortezomib (BZ) against HGSOC cells having differential sensitivities to cisplatin (CDDP). NFV caused cell cycle arrest associated with increased expression of cyclin-dependent kinase inhibitor p27kip1, while triggering the unfolded protein response (UPR) in a dose-dependent manner and assessed by increased subrogate ER stress biomarkers GRP78 and CHOP. We also discovered that blocking the ubiquitin proteasome system (UPS) using cytostatic concentrations of BZ causes accumulation of poly-ubiquitinated proteins and further activation of the UPR. More importantly, when we combined BZ with NFV, we observed a potentiation of the action of BZ leading to HGSOC lethality regardless of Pt sensitivity. These results suggest that NFV could potentially be used following standard Pt-based treatment, either as monotherapy or in conjunction with proteasome inhibitors, to kill the remaining HGSOC cells that otherwise recur and recreate the disease. In addition, the data provide the rationale for rapid repurposing to treat HGSOC of two drugs clinically approved for other uses, as their systemic toxicities have already been assessed. Citation Format: Mahbuba R. Subeha, Alicia A. Goyeneche, Michael A. Lisio, Carlos M. Telleria. The HIV protease inhibitor nelfinavir, alone or in combination with the proteasome inhibitor bortezomib, is cytotoxic to high-grade serous ovarian cancer cells regardless of platinum sensitivity [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A74.
Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal
Authors: David Tamborero, Rodrigo Dienstmann, Maan Haj Rachid, Jorrit Boekel, Richard Baird, Irene Braña, Luigi De Petris, Jeffrey Yachnin, Christophe Massard, Frans L. Opdam, Richard Schlenk, Claudio Vernieri, Elena Garralda, Michele Masucci, Xenia Villalobos, Elena Chavarria, Shubha Anand, Analía Azaro, Danny Baars, Svetlana Bajalica-Lagercrantz, Judith Balmaña, Jonas Bergh, Mariska Bierkens, Lennart Blomqvist, Gary J. Doherty, Arnauld Forest, Valentina Fornerone, Ionut Gabriel Funingana, Paola Gabaldi, Johan Hartman, Peter Horak, Claes Karlsson, Mary Kasanicki, Simon Kreutzfeldt, Rolf Lewensohn, Johan Lindberg, Carlos Lopez, Andreas Lundqvist, Patricia Martin-Romano, Jose-Ezequiel Martin, Gerrit Meijer, Susana Muñoz, Maud Ngo Camus, Claudio Nicotra, Paolo Nuciforo, Petra Oberrauch, Päivi Östling, Alejandro Piris-Giménez, Elena Provenzano, Etienne Rouleau, John Rowell, Omar Saavedra, Ignacio Sánchez Valdivia, Giovanni Scoazec, Kenneth Seamon, Marc Tischkowitz, Lizet van der Kolk, Ruud van der Noll, Daniel Vis, Ana Vivancos, Christina von Gertten, Anders Wennborg, Lodewyk Wessels, Valtteri Wirta, Julia Wolfart, Fabien Calvo, Stefan Fröhling, Alexander Eggermont, Giovanni Apolone, Emile E. Voest, Carlos Caldas, Josep Tabernero, Ingemar Ernberg, Jordi Rodon, Janne Lehtiö
Journal: Nature Medicine (2020)
Strategies used by transmasculine and non-binary adults assigned female at birth to resist transgender stigma in healthcare
Authors: Kristie L. Seelman, Tonia Poteat
Journal: International Journal of Transgender Health (2020)

Background: Transgender stigma is rampant within healthcare systems in the United States. Transgender adults assigned female at birth - including those identifying as transmasculine or non-binary - face unique barriers, such as stigma when accessing sexual and reproductive healthcare labeled as being for "women." However, transgender and non-binary people are not passive victims to this stigma, and the medical community would benefit from understanding the actions this population takes to resist and reduce transgender stigma in healthcare. Yet, little research has attempted to understand such actions. Aims: This qualitative study aims to explore how transmasculine and non-binary adults are actively resisting and reducing the impact of transgender stigma in healthcare. Methods: In-depth semi-structured interviews were conducted with 25 transmasculine and non-binary adults assigned female at birth who were living in a metropolitan area in the mid-Atlantic United States. The research team analyzed qualitative interview data using content analysis. Results: The 25 participants ranged in age from 21 to 57, with an average age of 33 years old. Six themes were identified related to resisting and reducing transgender stigma in healthcare: (a) using social support; (b) persistence to meet one's own needs; (c) avoiding mainstream healthcare; (d) advocacy; (e) doing one's own research; and (f) strategic disclosure of transgender/non-binary identity. We detail how privilege and intersectionality connect to the use of these strategies. Discussion: Findings indicate there is value in using peer advocates and peer health literacy; in developing and nurturing support groups related to transgender/non-binary health; in developing "allies" employed within the healthcare system; in creating and maintaining lists of culturally responsive health providers and resources about navigating the healthcare system; and in offering trainings related to self-advocacy and health-related activism. These findings can be used to inform future health prevention and intervention efforts with transmasculine and non-binary adults.
Randomized Trial of Amoxicillin for Pneumonia in Pakistan
Authors: Fyezah Jehan, Imran Nisar, Salima Kerai, Benazir Balouch, Nick Brown, Najeeb Rahman, Arjumand Rizvi, Yasir Shafiq, Anita K.M. Zaidi
Journal: New England Journal of Medicine (2020)

The World Health Organization (WHO) recommends oral amoxicillin for patients who have pneumonia with tachypnea, yet trial data indicate that not using amoxicillin to treat this condition may be noninferior to using amoxicillin.We conducted a double-blind, randomized, placebo-controlled noninferiority trial involving children at primary health care centers in low-income communities in Karachi, Pakistan. Children who were 2 to 59 months of age and who met WHO criteria for nonsevere pneumonia with tachypnea were randomly assigned to a 3-day course of a suspension of amoxicillin (the active control) of 50 mg per milliliter or matched volume of placebo (the test regimen), according to WHO weight bands (500 mg every 12 hours for a weight of 4 to <10 kg, 1000 mg every 12 hours for a weight of 10 to <14 kg, or 1500 mg every 12 hours for a weight of 14 to <20 kg). The primary outcome was treatment failure during the 3-day course of amoxicillin or placebo. The prespecified noninferiority margin was 1.75 percentage points.From November 9, 2014, through November 30, 2017, a total of 4002 children underwent randomization (1999 in the placebo group and 2003 in the amoxicillin group). In the per-protocol analysis, the incidence of treatment failure was 4.9% among placebo recipients (95 of 1927 children) and 2.6% among amoxicillin recipients (51 of 1929 children) (between-group difference, 2.3 percentage points; 95% confidence interval [CI], 0.9 to 3.7). Results were similar in the intention-to-treat analysis. The presence of fever and wheeze predicted treatment failure. The number needed to treat to prevent one treatment failure was 44 (95% CI, 31 to 80). One patient (<0.1%) in each group died. Relapse occurred in 40 children (2.2%) in the placebo group and in 58 children (3.1%) in the amoxicillin group.Among children younger than 5 years of age with nonsevere pneumonia, the frequency of treatment failure was higher in the placebo group than in the amoxicillin group, a difference that did not meet the noninferiority margin for placebo. (Funded by the Joint Global Health Trials Scheme [of the Department for International Development, Medical Research Council, and Wellcome] and others; RETAPP ClinicalTrials.gov number, NCT02372461.).
Stress Ulcer Prophylaxis for ICU Patients
Authors: Aylin Tansel, David Y. Graham
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
Enhanced efficacy of mesothelin-targeted immunotoxin LMB-100 and anti–PD-1 antibody in patients with mesothelioma and mouse tumor models
Authors: Qun Jiang, Azam Ghafoor, Idrees Mian, Daniel Rathkey, Anish Thomas, Christine Alewine, Manjistha Sengupta, Mark A. Ahlman, Jingli Zhang, Betsy Morrow, Seth M. Steinberg, Ira Pastan, Raffit Hassan
Journal: Science Translational Medicine (2020)

Mesothelin-targeted immunotoxin LMB-100 with anti–PD-1 antibody enhanced antitumor activity in patients with mesothelioma and mouse tumor models.