tbuckley/cabot-search huggingface dataset:
AB1048 RHUPUS SYNDROME IN A TERTIARY HOSPITAL
Authors: I. Martínez Cordellat, R. Gonzalez Mazario, M. De la Rubia Navarro, C. Pávez Perales, S. Leal Rodriguez, J. Ivorra Cortés, I. Chalmeta Verdejo, E. Grau García, C. Alcañiz Escandell, J. J. Fragio-Gil, L. Gonzalez Puig, R. Negueroles Albuixech, J. E. Oller Rodríguez, F. M. Ortiz Sanjuan, E. Vicens Bernabeu, C. Nájera Herranz, I. Cánovas Olmos, J. A. Román Ivorra
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rhupus syndrome (RhS) is a rare combination of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Different studies describe RhS cases that begin with erosive arthritis and the presence of rheumatoid factor (RF) and/or anti CCP and then the SLE symptoms. Objectives: Despite the fact that RhS shows a low prevalence, it would be useful to know clinical characteristics of RhS patients since their therapy and outcome differ from those having RA or SLE alone. Methods: Retrospective study with systematic revision of electronic clinical records of RhS patients was performed. Demographic, clinical and immunological data were collected. Results: Eight RhS patients were included (all fulfilled SLICC 2012 criteria for SLE and ACR 2010 for RA). Mean age was 67.3 (45-84) years (7 were female). In 3 cases RA was the first diagnosis with a mean evolution of 4.5 years until SLE diagnosis. In contrast, in 5 cases SLE was the first diagnosis with a mean evolution of 7.2 years until RA diagnosis. Photosensitivity and arthritis were the predominant clinical manifestations. One patient presents pericarditis and other case showed rheumatoid nodules in elbows. Renal, pulmonary or neurological affection was no reported. 4 patients were under biological/JAK inhibitors therapies (2 abatacept, 1 rituximab and 1 baricitinib) with favorable response of treatment. Conclusion: In contrast to other series, only the 37.5% of our RhS cases begins with polyarticular seropositive arthritis. The 62.5% started with SLE symptoms as haematological alterations, cutaneous and serological manifestation, and showed longer progression to have polyarticular affection. Thus, RhS diagnosis is earlier in patients that begin with RA symptoms. 4 RhS patients were refractory to DMARd treatments, where biological/JAK inhibitors therapies are needed. Disclosure of Interests: None declared
Potential Change in Insulin Out-of-Pocket Spending Under Cost-Sharing Caps Among Pediatric Patients With Type 1 Diabetes
Authors: Kao-Ping Chua, Joyce M. Lee, Rena M. Conti
Journal: JAMA Pediatrics (2020)

With Type 1 DiabetesTo improve insulin affordability, several states and insurers have implemented cost-sharing caps.For example, Colorado implemented a $100 cap for a 30-day insulin supply, while the insurer Cigna implemented a $25 cap. [1]2][3] We estimated the po-tential change in insulin out-of-pocket spending among privately insured children and young adults with type 1 diabetes if national $25 and $100 caps were implemented.Methods | We conducted a cross-sectional analysis of the 2018 IBM MarketScan Commercial Database, which includes nonelderly patients across the US with private insurance coverage from medium to large employers. 4We included patients aged 1 to 21 years with continuous enrollment in 2018, 1 or more Table.Annual Insulin Out-of-Pocket (OOP) Spending Under $25 and $100 Monthly Caps Among Pediatric Patients With Type 1 Diabetes Overall and by High-Deductible Health Plan (HDHP) Enrollment a,b Category Outcome Cap, Mean (SD), $ $25 $100 All patients (N = 12 185) c Patients who would benefit from cap No. (%) 7302 (59.9) 2151 (17.7)Annual OOP spending without cap 741 (720) 1343 (1017) Annual OOP spending with cap d 261 (139) 786 (422) Decrease in annual OOP spending with cap e 481 (683) 558 (873) Patients who would not benefit from cap No. (%) 4883 (40.1) 10 034 (82.3)Annual OOP spending with or without cap 124 (134) 312 (296) All patients Annual OOP spending without cap 494 (640) 494 (640) Annual OOP spending with cap d 206 (153) 395 (369) Decrease in annual OOP spending with cap e 288 (579) 98 (424) HDHP enrollees (n = 3116) HDHP enrollees who would benefit from cap No. (%) 2277 (73.1) 994 (31.9)Annual OOP spending without cap 866 (752) 1342 (879) Annual OOP spending with cap d 237 (133) 793 (411) Decrease in annual OOP spending with cap e 628 (706) 549 (735) HDHP enrollees who would not benefit from cap No. (%) 839 (26.9) 2122 (68.1)Annual OOP spending with or without cap 39 (74) 316 (330) All HDHP enrollees Annual OOP spending without cap 643 (741) 643 (741) Annual OOP spending with cap d 184 (149) 468 (421) Decrease in annual OOP spending with cap e 459 (664) 175 (488) Non-HDHP enrollees (n = 9069) Non-HDHP enrollees who would benefit from cap No. (%) 5025 (55.4) 1157 (12.8)Annual OOP spending without cap 685 (697) 1344 (1122) Annual OOP spending with cap d 271 (141) 779 (431) Decrease in annual OOP spending with cap e 414 (662) 565 (976) Non-HDHP enrollees who would not benefit from cap No. (%) 4044 (44.6) 7912 (87.2) Annual OOP spending with or without cap 141 (137) 311 (287) All non-HDHP enrollees Annual OOP spending without cap 443 (592) 443 (592) Annual OOP spending with cap d 213 (153) 371 (346) Decrease in annual OOP spending with cap e
Do No Harm
Authors: Nitin A. Kapur
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 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
Correction to: N0332 phase 2 trial of weekly irinotecan hydrochloride and docetaxel in refractory metastatic breast cancer: a North Central Cancer Treatment Group (NCCTG) Trial
Authors: W.W. Tan, D.W. Hillman, M. Salim, D.W. Northfelt, D.M. Anderson, P.J. Stella, R. Niedringhaus, A.M. Bernath, S.S. Gamini, F. Palmieri, E.A. Perez
Journal: Annals of Oncology (2018)

Ann Oncol 2010; 21: 493–497 (doi: 10.1093/annonc/mdp328) The following funding statement was missing from the original manuscript: ‘Supported by NIH grant U10CA025224 to the North Central Cancer Treatment Program.’ This has now been amended in the online version. Proteinuria and favourable clinical response in a patient receiving paclitaxel + bevacizumab for metastatic breast cancerAnnals of OncologyVol. 21Issue 8PreviewProteinuria is among the most common adverse reactions of bevacizumab (21%–64%) [1]. To our knowledge, there are no reports correlating bevacizumab-associated proteinuria and clinical outcome. We report the case of a patient who developed proteinuria and achieved clinical complete remission of metastatic breast cancer while receiving bevacizumab and paclitaxel. Full-Text PDF Open Archive
An emerging role of regulatory T-cells in cardiovascular repair and regeneration
Authors: Tiffany H.W. Fung, Kevin Y. Yang, Kathy O. Lui
Journal: Theranostics (2020)

Accumulating evidence has demonstrated that immune cells play an important role in the regulation of tissue repair and regeneration. After injury, danger signals released by the damaged tissue trigger the initial pro-inflammatory phase essential for removing pathogens or cellular debris that is later replaced by the anti-inflammatory phase responsible for tissue healing. On the other hand, impaired immune regulation can lead to excessive scarring and fibrosis that could be detrimental for the restoration of organ function. Regulatory T-cells (Treg) have been revealed as the master regulator of the immune system that have both the immune and regenerative functions. In this review, we will summarize their immune role in the induction and maintenance of self-tolerance; as well as their regenerative role in directing tissue specific response for repair and regeneration. The latter is clearly demonstrated when Treg enhance the differentiation of stem or progenitor cells such as satellite cells to replace the damaged skeletal muscle, as well as the proliferation of parenchymal cells including neonatal cardiomyocytes for functional regeneration. Moreover, we will also discuss the reparative and regenerative role of Treg with a particular focus on blood vessels and cardiac tissues. Last but not least, we will describe the ongoing clinical trials with Treg in the treatment of autoimmune diseases that could give clinically relevant insights into the development of Treg therapy targeting tissue repair and regeneration.
Bioethics Emergencies Can Be Used to Perform a Real-World Test of Utilitarian Policies
Authors: Mark Fedyk, Hugh Black, Mark Yarborough, Nathan Fairman, Neil S. Wenger
Journal: The American Journal of Bioethics (2020)

Utilitarian approaches to ethical problems often appear to be more practical than many alternatives: we can know what the right course of action is by calculating whichever choice will produce the ...
House Dust Mite Specific Antibodies induce Neutrophilic Inflammation in the Heart
Authors: Xiao Chen, Yuan-Yi Zhang, Dongting Ye, Gui Yang, Yan-Nan Song, Li-Hua Mo, Ping-Chang Yang, Jiang-Ping Song
Journal: Theranostics (2020)

Rationale: Inflammatory heart disorders are among the causes of human death. The causative factors of heart inflammation are to be further elucidated. House dust mite (HDM)-derived protein antigens are involved in the pathogenesis of many human diseases. This study aims to investigate the role of HDM-specific autoantibodies in the pathogenesis of heart inflammation. Methods: Human heart tissue samples were obtained from surgically removed hearts in heart transplantation. The interaction of the heart tissues with HDM-specific antibodies was assessed by pertinent immune analysis. The role of HDM-specific autoantibodies in the induction of heart inflammation was assessed with a murine model. Results: HDM-specific IgG (mIgG) was detected in the serum of patients with myocarditis (Mcd); the mIgG titers were positively correlated with the neutrophil counts in the heart tissues. The mIgG specifically bound to keratin-10 (KRT10) in heart vascular endothelial cells and the heart tissue protein extracts. The amounts of C3a, C5a and C5b-9 were increased in the mouse heart tissues after exposing to mIgG. In the presence of the complement-containing serum, mIgG bound cardiovascular epithelial monolayers to impair the barrier functions. Administration of mIgG or HDM induced the Mcd-like inflammation in the heart, in which neutrophils were the dominant cellular components in the infiltration of inflammatory cells. Conclusions: Mcd patients with neutrophilic inflammation in the heart had higher serum levels of mIgG. The mIgG bound heart endothelial cells to impair the endothelial barrier functions and induce neutrophilic inflammation in the heart.
Exploiting the Therapeutic Interaction of WNT Pathway Activation and Asparaginase for Colorectal Cancer Therapy
Authors: Laura Hinze, Roxane Labrosse, James Degar, Teng Han, Emma M. Schatoff, Sabine Schreek, Salmaan Karim, Connor McGuckin, Joshua R. Sacher, Florence Wagner, Martin Stanulla, Chen Yuan, Ewa Sicinska, Marios Giannakis, Kimmie Ng, Lukas E. Dow, Alejandro Gutierrez
Journal: Cancer Discovery (2020)

Abstract Colorectal cancer is driven by mutations that activate canonical WNT/β-catenin signaling, but inhibiting WNT has significant on-target toxicity, and there are no approved therapies targeting dominant oncogenic drivers. We recently found that activating a β-catenin–independent branch of WNT signaling that inhibits GSK3-dependent protein degradation induces asparaginase sensitivity in drug-resistant leukemias. To test predictions from our model, we turned to colorectal cancer because these cancers can have WNT-activating mutations that function either upstream (i.e., R-spondin fusions) or downstream (APC or β-catenin mutations) of GSK3, thus allowing WNT/β-catenin and WNT-induced asparaginase sensitivity to be unlinked genetically. We found that asparaginase had little efficacy in APC or β-catenin–mutant colorectal cancer, but was profoundly toxic in the setting of R-spondin fusions. Pharmacologic GSK3α inhibition was sufficient for asparaginase sensitization in APC or β-catenin–mutant colorectal cancer, but not in normal intestinal progenitors. Our findings demonstrate that WNT-induced therapeutic vulnerabilities can be exploited for colorectal cancer therapy. Significance: Solid tumors are thought to be asparaginase-resistant via de novo asparagine synthesis. In leukemia, GSK3α-dependent protein degradation, a catabolic amino acid source, mediates asparaginase resistance. We found that asparaginase is profoundly toxic to colorectal cancers with WNT-activating mutations that inhibit GSK3. Aberrant WNT activation can provide a therapeutic vulnerability in colorectal cancer. See related commentary by Davidsen and Sullivan, p. 1632. This article is highlighted in the In This Issue feature, p. 1611
The unsettled science of nonrenal calcitriol production and its clinical relevance
Authors: J. Wesley Pike, Mark B. Meyer
Journal: Journal of Clinical Investigation (2020)

The primary function of vitamin D in higher vertebrates is to regulate mineral homeostasis through direct actions on intestinal calcium and phosphate absorption, bone mineral resorption, and renal mineral reabsorption  Vitamin D itself is inactive and must undergo sequential modification via two specific chemical reactions, first in the liver to 25(OH)D3 by the enzyme CYP2R1, and then in the kidney to 1,25-dihydroxyvitamin D3 by the tightly regulated enzyme CYP27B1  Calcitriol, whose level is also modulated via renal CYP24A1-mediated degradation, is then secreted into the blood as an active endocrine hormone and delivered to distant target tissues  Here, Pike and Meyer discuss the importance of adequate blood levels of vitamin D and the models for characterizing features of NRTC calcitriol production
Genetic engineering of novel super long-acting Exendin-4 chimeric protein for effective treatment of metabolic and cognitive complications of obesity
Authors: Jong Youl Lee, Taehoon Park, Eunmi Hong, Reeju Amatya, Kyung-Ah Park, Young-Hoon Park, Kyoung Ah Min, Minki Jin, Sumi Lee, Seungmi Hwang, Gu Seob Roh, Meong Cheol Shin
Journal: Biomaterials (2020)
Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid. A Prospective Multicountry Study
Authors: Molly F. Franke, Palwasha Khan, Cathy Hewison, Uzma Khan, Helena Huerga, Kwonjune J. Seung, Michael L. Rich, Khin Zarli, Nazgul Samieva, Lawrence Oyewusi, Parvati Nair, Mishaz Mudassar, Nara Melikyan, Putri Lenggogeni, Leonid Lecca, Andargachew Kumsa, Munira Khan, Shirajul Islam, Kerow Hussein, Wisny Docteur, Nino Chumburidze, Elmira Berikova, Hakob Atshemyan, Sidney Atwood, Manzurul Alam, Saman Ahmed, Mathieu Bastard, Carole D. Mitnick
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Bedaquiline and delamanid offer the possibility of more effective and less toxic treatment for multidrug-resistant (MDR) tuberculosis (TB). With this treatment, however, some patients remain at high risk for an unfavorable treatment outcome. The endTB Observational Study is the largest multicountry cohort of patients with rifampin-resistant TB or MDR-TB treated in routine care with delamanid- and/or bedaquiline-containing regimens according to World Health Organization guidance.Objectives: We report the frequency of sputum culture conversion within 6 months of treatment initiation and the risk factors for nonconversion.Methods: We included patients with a positive baseline culture who initiated a first endTB regimen before April 2018. Two consecutive negative cultures collected 15 days or more apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups.Measurements and Main Results: A total of 1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%), or both (10%). Of these, 939 (85%) experienced culture conversion within 6 months. In adjusted analyses, patients with HIV had a lower probability of conversion (0.73; 95% confidence interval [CI], 0.62-0.84) than patients without HIV (0.84; 95% CI, 0.79-0.90; P = 0.03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0.68; 95% CI, 0.57-0.79) relative to patients without either (0.89; 95% CI, 0.84-0.95; P = 0.0004). Hepatitis C infection, diabetes mellitus or glucose intolerance, and baseline resistance were not associated with conversion.Conclusions: Frequent sputum conversion in patients with rifampin-resistant TB or MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease.
Recession Increases Need for Intensive Care in Pediatric Hematologic Malignancy Presentation
Authors: Lena E. Winestone, Kelly D Getz, Yimei Li, Rebecca Citrin, Yuan-Shung V. Huang, Kira Bona, Emily DePaul, Alix E. Seif, Julie C Fitzgerald, Brian T Fisher, Richard Aplenc
Journal: Blood (2017)
Epigenetic Suppression of Transgenic T-cell Receptor Expression via Gamma-Retroviral Vector Methylation in Adoptive Cell Transfer Therapy
Authors: Theodore S. Nowicki, Colin Farrell, Marco Morselli, Liudmilla Rubbi, Katie M. Campbell, Mignonette H. Macabali, Beata Berent-Maoz, Begoña Comin-Anduix, Matteo Pellegrini, Antoni Ribas
Journal: Cancer Discovery (2020)

Abstract Transgenic T-cell receptor (TCR) adoptive cell therapies recognizing tumor antigens are associated with robust initial response rates, but frequent disease relapse. This usually occurs in the setting of poor long-term persistence of cells expressing the transgenic TCR, generated using murine stem cell virus (MSCV) γ-retroviral vectors. Analysis of clinical transgenic adoptive cell therapy products in vivo revealed that despite strong persistence of the transgenic TCR DNA sequence over time, its expression was profoundly decreased over time at the RNA and protein levels. Patients with the greatest degrees of expression suppression displayed significant increases in DNA methylation over time within the MSCV promoter region, as well as progressive increases in DNA methylation within the entire MSCV vector over time. These increases in vector methylation occurred independently of its integration site within the host genomes. These results have significant implications for the design of future viral vector gene–engineered adoptive cell transfer therapies. Significance: Cellular immunotherapies' reliance on retroviral vectors encoding foreign genetic material can be vulnerable to progressive acquisition of DNA methylation and subsequent epigenetic suppression of the transgenic product in TCR adoptive cell therapy. This must be considered in the design of future generations of cellular immunotherapies for cancer. This article is highlighted in the In This Issue feature, p. 1611
AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients
Authors: Allegra Kaufman, Lubna Abuqayyas, William S. Denney, Erik J. Tillman, Tim Rolph
Journal: Cell Reports Medicine (2020)

Experimental fibroblast growth factor 21 (FGF21) analogs can improve lipid profiles in patients with metabolic diseases. However, their effects on markers of insulin sensitivity appear to be minimal, potentially because of insufficient exposure. Systemic drug levels vary from sub-pharmacological to demonstrating pharmacodynamic effects but with dose-limiting adverse events. Here we report results from a phase 1 multiple ascending dose study of AKR-001, an Fc-FGF21 fusion protein engineered for sustained systemic pharmacologic exposure, in individuals with type 2 diabetes. With a half-life of 3–3.5 days, the peak-to-trough ratio under steady-state conditions is approximately 2 following QW dosing. AKR-001 appears to demonstrate pharmacodynamic effects on serum markers of insulin sensitivity and acceptable tolerability up to and including 70 mg QW. Positive trends in lipoprotein profile, including triglycerides, non-high-density lipoprotein (non-HDL) cholesterol, HDL-C, and apolipoproteins B and C3 are consistent with other FGF21 analogs. AKR-001’s clinical profile supports further evaluation as a treatment for metabolic diseases.
Epidemiology of varicella among immigrants and non-immigrants in Quebec, Canada, before and after the introduction of childhood varicella vaccination: a retrospective cohort study
Authors: Christina Greenaway, Zoe R Greenwald, Arash Akaberi, Sunny Song, Ana Maria Passos-Castilho, Claire Nour Abou Chakra, Adam Palayew, Balquis Alabdulkarim, Robert Platt, Laurent Azoulay, Marc Brisson, Caroline Quach
Journal: The Lancet Infectious Diseases (2020)
Inhaled Liposomal Antimicrobial Delivery in Lung Infections
Authors: Matteo Bassetti, Antonio Vena, Alessandro Russo, Maddalena Peghin
Journal: Drugs (2020)

The management of difficult-to-treat acute and chronic respiratory infections (infections in cystic fibrosis, non-cystic fibrosis bronchiectasis, immunocompromised and mechanically ventilated patients) and difficult-to-treat pathogens (including multidrug-resistant strains) has become a challenge in clinical practice. The arsenal of conventional antibiotic drugs can be limited by tissue penetration, toxicities, or increasing antibiotic resistance. Inhaled antimicrobials are an interesting therapeutic approach for optimizing the management of respiratory infections. Due to extensive developments in liposome technology, a number of inhaled liposome-based antibiotic and antifungal formulations are available for human use and many products are undergoing clinical trials. Liposomes are biocompatible, biodegradable, and nontoxic vesicles able to encapsulate and carry antimicrobials, enhancing the therapeutic index of various agents and retention at the desired target within the lung. Liposomes reduce drug toxicity and improve tolerability, leading to better compliance and to decreased respiratory side effects. The aim of this article was to provide an up-to-date overview of nebulized liposomal antimicrobials for lung infections (with a special focus on liposomal amikacin, tobramycin, ciprofloxacin, and amphotericin B for inhalation), discussing the feasibility and therapeutic potential of these new strategies of preventing and treating bacteria, mycobacterial and fungal infections.
Profound and redundant functions of arcuate neurons in obesity development
Authors: Canjun Zhu, Zhiying Jiang, Yuanzhong Xu, Zhao-Lin Cai, Qingyan Jiang, Yong Xu, Mingshan Xue, Benjamin R. Arenkiel, Qi Wu, Gang Shu, Qingchun Tong
Journal: Nature Metabolism (2020)