tbuckley/cabot-search huggingface dataset:
Robotic Surgery and Oncologic Outcomes
Authors: Yinin Hu, Vivian E. Strong
Journal: JAMA Oncology (2020)

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Hypoxia-inducible factors and diabetes
Authors: Jenny E. Gunton
Journal: Journal of Clinical Investigation (2020)

Hypoxia can be defined as a relative deficiency in the amount of oxygen reaching the tissues. Hypoxia-inducible factors (HIFs) are critical regulators of the mammalian response to hypoxia. In normal circumstances, HIF-1α protein turnover is rapid, and hyperglycemia further destabilizes the protein. In addition to their role in diabetes pathogenesis, HIFs are implicated in development of the microvascular and macrovascular complications of diabetes. Improving glucose control in people with diabetes increases HIF-1α protein and has wide-ranging benefits, some of which are at least partially mediated by HIF-1α. Nevertheless, most strategies to improve diabetes or its complications via regulation of HIF-1α have not currently proven to be clinically useful. The intersection of HIF biology with diabetes is a complex area in which many further questions remain, especially regarding the well-conducted studies clearly describing discrepant effects of different methods of increasing HIF-1α, even within the same tissues. This Review presents a brief overview of HIFs; discusses the range of evidence implicating HIFs in β cell dysfunction, diabetes pathogenesis, and diabetes complications; and examines the differing outcomes of HIF-targeting approaches in these conditions.
Human Immunodeficiency Virus (HIV)-Resistant CD4+ UT-7 Megakaryocytic Human Cell Line Becomes Highly HIV-1 and HIV-2 Susceptible Upon CXCR4 Transfection: Induction of Cell Differentiation by HIV-1 Infection
Authors: Marta Baiocchi, Eleonora Olivetta, Cristiana Chelucci, Anna Claudia Santarcangelo, Roberta Bona, Paola d'Aloja, Ugo Testa, Norio Komatsu, Paola Verani, Maurizio Federico
Journal: Blood (1997)
A phase II study of capecitabine-oxaliplatin and cetuximab in patients (pts) with advanced/metastatic gastric cancer (G) or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Syma Iqbal, Anthony B. El-Khoueiry, Dongyun Yang, David Páez, Vinay Duddalwar, Wu Zhang, Raluca Dana Agafitei, Ramona Lujan, Sarah Cole, Yan Ning, Rita El-Khoueiry, Fotios Loupakis, Takeru Wakatsuki, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2012)

4096 Background: There have been limited advances in the treatment (tx) of pts with metastatic G or GEJ adenocarcinoma. The combination of fluroropyrimidines and platinums are standard regimens for this disease. The epidermal growth factor receptor pathway has been identified as a target and KRAS mutations are rare. Methods: The primary objective was to assess the proportion of pts with progression within 4 months. Secondary objectives include response (RR), progression free survival (PFS) overall survival (OS), toxicity and molecular correlates. A two-stage Simon phase II design was used to distinguish between a 30% vs. 50% 4 month PFS; with analysis planned at 27 and 53 pts. Eligible pts were chemonaive, metastatic/unresectable with measurable disease. Pts received capecitabine 850 mg/m2 BID D1-14, oxaliplatin 130 mg/m 2 IV D1, cetuximab 400 mg/m2 (load) then 250 mg/m 2 IV D1, 8, 15, q21 days. Blood and tissue were analyzed for genes in the DNA repair and EGFR pathways. Results: 61 pts were accrued, 2 GEJ and 59 G; 42 male, 19 female; median age 56 years (28-86); 54 pts were evaluable. The 4 month PFS rate 61% (95%CI 47-73%), PFS 5.4 months (95% CI 3.5-6.7); RR 50% (95%CI: 36-64%), 1 (1.9%) complete, 26 (48.1%) partial, 22 (40.7%) stable disease; 2 (3.7%) pts became resectable; median OS 14.9 months (95% CI 8.8-22.2) with median follow-up of 21.8 months. 65% (39/60) of pts had grade 3 (36 pts) or 4 (3 pts) toxicity; most common, anorexia (13.3%), diarrhea (13.3%), fatigue (13.3%), nausea (15%), vomiting (15%); grade 3 hand/foot (5.3%), acneiform rash (3.3%). SNP’s in LRIG4, (regulator of EGF signaling) and PAI1 (tumor angiogenesis, cell proliferation, migration and adhesion) were significantly associated with RR (67% G/G vs 17% A/A ,p=0.044) and PFS (5.8 months 5G/4G vs 3.4 months 5G/5G, p=0.017) respectively. Conclusions: XELOX and cetuximab has promising activity, comparable to existing regimens. Novel SNP’s were identified correlating with RR and PFS which may allow for optimization of pt selection.
Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia
Authors: HJ Deeg, R Storb, ED Thomas, N Flournoy, MS Kennedy, M Banaji, FR Appelbaum, WI Bensinger, CD Buckner, RA Clift
Journal: Blood (1985)
Treatment of Elderly Non–small Cell Lung Cancer Patients with Three Different Schedules of Weekly Paclitaxel in Combination with Carboplatin: Subanalysis of a Randomized Trial
Authors: Suresh Ramalingam, John Barstis, Michael C. Perry, Renato V. La Rocca, Sreenivasa R. Nattam, David Rinaldi, Ray Clark, Glenn M. Mills, Chandra P. Belani
Journal: Journal of Thoracic Oncology (2006)
Management of thrombotic microangiopathy in pregnancy and postpartum: report from an international working group
Authors: Fadi Fakhouri, Marie Scully, François Provôt, Miquel Blasco, Paul Coppo, Marina Noris, Kathy Paizis, David Kavanagh, Frédéric Pène, Sol Quezada, Alexandre Hertig, Sébastien Kissling, Patrick O’Brien, Yahsou Delmas, Lorenzo Alberio, Norbert Winer, Agnès Veyradier, Spero Cataland, Véronique Frémeaux-Bacchi, Chantal Loirat, Giuseppe Remuzzi, Vassilis Tsatsaris
Journal: Blood (2020)
Challenge of diagnosing ANCA-associated vasculitis during COVID-19 pandemic: a missed ‘window of opportunity’
Authors: Alessandro Giollo, Riccardo Bixio, Davide Gatti, Ombretta Viapiana, Luca Idolazzi, Christian Dejaco, Maurizio Rossini
Journal: Annals of the Rheumatic Diseases (2020)

There is concern around coronavirus disease 2019 (COVID-19) and rheumatic diseases. Systemic vasculitis was the fourth most common rheumatic disease among patients hospitalised for COVID-19.1 However, the diagnosis of anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitis (AAV) can be challenging during COVID-19 pandemic for several reasons: first, clinical presentation of patients with AAV partially overlaps with COVID-19; second, patients with initial symptoms of AAV may be concerned to seek medical help in order not to get into close contact with other patients; and third, diagnosis may be delayed because non-urgent tests and visits might have been postponed due to COVID-19 related closure of services. Herein, we report the poor and irreversible clinical outcomes of diagnostic delay of AAV during the COVID-19 pandemic.

We recently encountered a cluster of nine life-threatening presentations of new-onset or relapsing AAV admitted to a Verona hospital, all negative for SARS-CoV-2 by nasopharyngeal swab or bronchoalveolar fluid aspiration. We compared clinical characteristics of this group presenting in the time frame of 6 weeks during the second trimester of 2020 …
Coeliac disease and risk of birth defects in pregnancy
Authors: Nathalie Auger, Amelie Therrien, Marianne Bilodeau-Bertrand, Chantal Nelson, Laura Arbour
Journal: Gut (2020)

Coeliac disease (CD) is prevalent in patients of reproductive age, but the impact on pregnancy and fetal development is unclear. The British Society of Gastroenterology recommends serological testing for CD in patients with chronic diarrhoea,1 but CD may be under-recognised in women without the classic symptoms.2 We studied the association between CD and the risk of birth defects in pregnant women.

We analysed a cohort of live births between 1989 and 2016 in Quebec, Canada using discharge summaries from the Maintenance and Use of Data for the Study of Hospital Clientele database. We used diagnostic codes to identify women with CD and infants with different types of birth defects. We determined whether CD was present during prenatal follow-up, or if women required hospitalisation for CD before or after pregnancy. We used log-binomial regression models with robust SE to estimate associations between CD and birth defects adjusted for maternal characteristics.

This study comprised 2 184 888 infants, including 125 081 …
Reply to Takimoto: Micronodular Pattern of Organizing Pneumonia or Hypersensitivity Pneumonia Induced by an Immune Checkpoint Inhibitor?
Authors: Masahiro Yamasaki, Masaya Taniwaki, Kazuma Kawamoto, Naoko Matsumoto, Kaori Hashimoto, Shinji Nabeshima, Nobuyuki Ohashi, Noboru Hattori
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Evaluation of Aspirin and Statin Therapy Use and Adherence in Patients With Premature Atherosclerotic Cardiovascular Disease
Authors: Dhruv Mahtta, David J. Ramsey, Mahmoud Al Rifai, Khurram Nasir, Zainab Samad, David Aguilar, Hani Jneid, Christie M. Ballantyne, Laura A. Petersen, Salim S. Virani
Journal: JAMA Network Open (2020)

Studies on the use of and adherence to secondary prevention therapies in patients with premature and extremely premature atherosclerotic cardiovascular disease (ASCVD) are lacking.To evaluate and compare aspirin use, any statin use, high-intensity statin use, and statin adherence among patients with premature or extremely premature ASCVD compared with patients with nonpremature ASCVD.This multicenter cross-sectional study used the clinical and administrative data sets of the US Department of Veterans Affairs (VA) to identify adult patients with at least 1 primary care visit in the VA health care system between October 1, 2014, and September 30, 2015. The study cohort comprised patients with ASCVD (ischemic heart disease, peripheral arterial disease, or ischemic cerebrovascular disease) who were enrolled in the Veterans With Premature Atherosclerosis (VITAL) registry. Patients with missing data for date of birth or sex and those with limited life expectancy were excluded. Data were analyzed from November 1, 2019, to January 1, 2020.Premature (the first ASCVD event occurred at age <55 years for men and age <65 years for women) vs nonpremature (the first ASCVD event occurred at age ≥55 years for men or age ≥65 years for women) ASCVD and extremely premature (the first ASCVD event occurred at age <40 years) vs nonpremature ASCVD.The primary outcomes were aspirin use, any statin use, high-intensity statin use, and statin adherence (measured by proportion of days covered [PDC] ≥0.8).Of the 1 248 158 patients identified, 135 703 (10.9%) had premature ASCVD (mean [SD] age, 49.6 [5.8] years; 116 739 men [86.0%]), 1 112 455 (89.1%) had nonpremature ASCVD (mean [SD] age, 69.6 [8.9] years; 1 104 318 men [99.3%]), and 7716 (0.6%) had extremely premature ASCVD (mean [SD] age, 34.2 [4.3] years; 6576 men [85.2%]). Patients with premature ASCVD vs those with nonpremature ASCVD had lower rates of aspirin use (96 468 [71.1%] vs 860 726 [77.4%]; P < .001) and any statin use (98 908 [72.9%] vs 894 931 [80.5%]; P < .001); had a statin PDC of 0.8 or higher (57 306 [57.9%] vs 644 357 [72.0%]; P < .001); and a higher rate of high-intensity statin use (49 354 [36.4%] vs 332 820 [29.9%]; P < .001). Similarly, patients with extremely premature ASCVD were less likely to use aspirin (odds ratio [OR], 0.27; 95% CI, 0.26-0.29), any statin (OR, 0.25; 95% CI, 0.24-0.27), or high-intensity statin (OR, 0.78; 95% CI, 0.74-0.82) and to be statin adherent (OR, 0.44; 95% CI, 0.41-0.47).In this study, patients with premature or extremely premature ASCVD appeared to be less likely to use aspirin or statins and to adhere to statin therapy. This finding warrants further investigation into premature ASCVD and initiatives, including clinician and patient education, to better understand and mitigate the disparities in medication use and adherence.
Covid-19: Care homes in Belgium and Spain had “alarming living conditions,” says MSF report
Authors: Jacqui Thornton
Journal: BMJ (2020)

A report into the global response to coronavirus outbreaks has heavily criticised the "alarming living conditions" in Belgian and Spanish care homes, the former being described as a "true humanitarian crisis."The report, 1 by Médecins Sans Frontières (MSF), documents the first phase of the non-governmental organisation's global covid-19 response from March until May.During that time it committed "substantial resources" both to developing dedicated covid-19 projects and to maintaining essential healthcare in its existing programmes worldwide, including interventions in Italy, Spain, Belgium, and France.Operations in the four European countries included projects supporting retirement and nursing homes, hospitals, and primary healthcare facilities, as well as providing protection and care to vulnerable groups in reception facilities, refugee camps, homeless shelters, and prisons.Smaller projects were set up in Portugal, the UK, and Switzerland.But it was Belgium and Spain where the living conditions-as well as the lack of protective equipment and sufficient personnel and the enormous emotional burden on caregivers in care homes-caused high concern.This led MSF to alert national authorities on "several occasions.
Effectiveness and Safety of Systemic Therapy for Psoriasis in Older Adults
Authors: Marieke E. C. van Winden, Lara S. van der Schoot, Mariluz van de L’Isle Arias, Lieke J. van Vugt, Juul M. P. A. van den Reek, Peter C. M. van de Kerkhof, Elke M. G. J. de Jong, Satish F. K. Lubeek
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> Treating older adults with psoriasis can be challenging owing to comorbidities, concomitant medication use, and consequent safety risks. Although many studies focus on the effectiveness and safety of systemic antipsoriatic therapies in the general population, their effectiveness in older adults with psoriasis has not been systematically assessed. <h3>Objective</h3> To evaluate the effectiveness and safety of systemic antipsoriatic therapies in patients 65 years or older. <h3>Evidence Review</h3> A systematic literature search was conducted in Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) on November 11, 2019. No date limit was used. Randomized clinical trials, cohort studies, large case series, and meta-analyses assessing efficacy (or effectiveness) and/or safety of systemic antipsoriatic therapies in patients 65 years or older were included. <h3>Findings</h3> The initial search yielded 11 096 results, of which 31 unique articles with 39 561 patients were included in analysis. Overall, limited data were available per systemic agent, and overall quality of the included studies on conventional systemic therapies was low. At the end of the induction phase (12-16 weeks after start of treatment), a reduction of 75% in Psoriasis Area and Severity Index was achieved in 49% of 74 methotrexate sodium users 65 years or older, 46% to 52.6% of 178 older cyclosporin users, 27% to 47.8% of 108 older acitretin users, 15.6% to 64% of 256 etanercept users 65 years or older, 66.7% to 93% of 43 infliximab users 65 years or older, 60.7% to 65% of 100 adalimumab users 65 years or older, 56.5% of 46 ustekinumab users 65 years or older, and 86.4% of 67 secukinumab users 65 years or older. Effectiveness of acitretin, etanercept, adalimumab, and secukinumab appeared not to be associated with age; studies regarding other systemic antipsoriatic therapies did not provide age group comparisons. Older age was significantly associated with renal function deterioration in cyclosporin users and with lymphopenia in fumaric acid esters users (hazard ratio, 2.42; 95% CI, 1.65-3.55;<i>P</i> &lt; .001). Infections were the most frequently reported adverse event in patients 65 years or older using biologics, but no significant association with age was found. <h3>Conclusions and Relevance</h3> On the basis of limited available evidence, age alone should not be a limiting factor in psoriasis management. Awareness of comorbidities and concomitant medication use is very important, as well as appropriate dosing and frequent laboratory and clinical monitoring. More real-world evidence and (sub)analyses of prospective cohort studies on the effectiveness and safety of systemic therapies in older adults are critical to optimize personalized, effective, and safe antipsoriatic management in this growing patient group.
Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma
Authors: Mark R. Middleton, Cheryl McAlpine, Victoria K. Woodcock, Pippa Corrie, Jeffrey R. Infante, Neil M. Steven, Thomas R. Jeffry Evans, Alan Anthoney, Alexander N. Shoushtari, Omid Hamid, Avinash Gupta, Antonella Vardeu, Emma Leach, Revashnee Naidoo, Sarah Stanhope, Sion Lewis, Jacob Hurst, Ita O’Kelly, Mario Sznol
Journal: Clinical Cancer Research (2020)

Tebentafusp is a first-in-class bispecific fusion protein designed to target gp100 (a melanoma-associated antigen) through a high affinity T-cell receptor (TCR) binding domain and an anti-CD3 T-cell engaging domain, which redirects T cells to kill gp100-expressing tumor cells. Here, we report a multicenter phase I/II trial of tebentafusp in metastatic melanoma (NCT01211262) focusing on the mechanism of action of tebentafusp.
Abstract 6599: Screening and characterization of AlloCAR T targeting DLL3 for the treatment of small cell lung cancer
Authors: Yi Zhang, Silvia Tacheva-Grigorova, Zea Melton, Bryan Smith, Tao Sai, Tom Van Blarcom, Rafael Amado, Barbra Sasu, Siler Panowski
Journal: Cancer Research (2020)

Abstract Small cell lung cancer (SCLC) is an aggressive disease with very limited treatment options. SCLC responsiveness to immuno-oncology agents suggests this indication may be amenable to a T-cell based therapy. Genetically modified T cells that express chimeric antigen receptors (CARs) have shown impressive efficacy in multiple hematological malignancies. To translate this approach for SCLC treatment, we are exploring Delta-like ligand 3 (DLL3) as a therapeutic target. DLL3 is highly expressed in SCLC and several other types of neuroendocrine cancers, with limited normal tissue RNA expression in brain, pituitary and testis. A large panel of antibodies that bind to DLL3 were generated, formatted into CARs, and tested in in vitro short-term and long-term cytotoxicity assays using target cells that express high, medium or low levels of DLL3. A subset of CAR T cells were highly active and displayed long-term killing potential. These were tested in vivo and robust efficacy was seen in both subcutaneous and systemic SCLC models. To understand the potential for toxicity in pituitary and brain, subcutaneous or intracranial tumors expressing DLL3 were implanted in mice and human/mouse cross-reactive DLL3 CAR T cells were injected into the tumor-bearing animals. In both models, T cell infiltration into intermediate and posterior pituitary was detected. However, no tissue damage in brain or pituitary was observed and hormone-secretion function of pituitary was not ablated. We believe toxicity is significantly derisked but as an additional safety assurance, CAR T cells were further engineered to contain an off-switch, by which CAR T cells are eliminated upon administration of Rituximab. Multiple off-switch CAR formats were evaluated, and optimal formats determined independently for each CAR. In summary, DLL3 is a target for SCLC with limited normal tissue expression and toxicity. Multiple DLL3 CAR T cells have been characterized. A subset of these CAR T cells showed robust in vitro and in vivo activity and were chosen for further evaluation as potential clinical candidates. Citation Format: Yi Zhang, Silvia Tacheva-Grigorova, Zea Melton, Bryan Smith, Tao Sai, Tom Van Blarcom, Rafael Amado, Barbra Sasu, Siler Panowski. Screening and characterization of AlloCAR T targeting DLL3 for the treatment of small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6599.
CONGO/CRIMEAN HÆMORRHAGIC FEVER IN DUBAI
Authors: Mustafa Nur El Huda Suleiman, J.M. Muscat-Baron, J.R. Harries, Abdel Gadir Osman Satti, G.S. Platt, E.T.W. Bowen, D.I.H. Simpson
Journal: The Lancet (1980)
Comment on Mizokami-Stout et al. The Contemporary Prevalence of Diabetic Neuropathy in Type 1 Diabetes: Findings From the T1D Exchange. Diabetes Care 2020;43:806–812
Authors: Karel Kostev
Journal: Diabetes Care (2020)

Mizokami-Stout et al. (1) investigated the prevalence of diabetic peripheral neuropathy (DPN) in individuals with type 1 diabetes (T1D) in the U.S. Among 5,936 individuals with T1D (mean ± SD age 39 ± 18 years, 55% female, mean ± SD glycated hemoglobin [HbA1c] 8.1 ± 1.6%), DPN prevalence was 11%. Older age, higher HbA1c, female sex, cardiovascular disease, hypertriglyceridemia, higher BMI, retinopathy, and reduced estimated glomerular filtration rate were associated with significantly higher risk of having DPN.

We conducted a similar study in Germany based on a longitudinal database (Disease Analyzer database) that …
Annals Graphic Medicine - Academic Medicine Monsters
Authors: Stefan Tigges
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 August 2020Annals Graphic Medicine - Academic Medicine MonstersFREEStefan Tigges, MDStefan Tigges, MDEmory University School of Medicine, Atlanta, Georgia (S.T.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0084 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Emory University School of Medicine, Atlanta, Georgia (S.T.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0084.Author/Illustrator Information: Stefan Tigges, MD (e-mail, [email protected]edu). PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 August 2020Volume 173, Issue 4Page: W69-W74KeywordsAcademic medicineConflicts of interestDisclosureHealth care ePublished: 18 August 2020 Issue Published: 18 August 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...