tbuckley/cabot-search huggingface dataset:
Long‐Term Outcomes After Transcatheter and Surgical Aortic Valve Replacement in Patients With Cirrhosis: A Guide for the Hepatologist
Authors: Thoetchai (Bee) Peeraphatdit, Vuyisile T. Nkomo, Niyada Naksuk, Douglas A. Simonetto, Nimish Thakral, Grant M. Spears, William S. Harmsen, Vijay H. Shah, Kevin L. Greason, Patrick S. Kamath
Journal: Hepatology (2020)

Background and Aims Hepatologists often determine whether transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) is preferred for patients with cirrhosis and severe aortic stenosis. The goal of this cohort study is to compare outcomes following TAVR and SAVR in patients with cirrhosis to inform the preferred intervention. Approach and Results Prospectively collected data on 105 consecutive patients with cirrhosis and aortic stenosis who underwent TAVR (n = 55) or SAVR (n = 50) between 2008 and 2016 were reviewed retrospectively. Two control groups were included: 2,680 patients without cirrhosis undergoing TAVR and SAVR and 17 patients with cirrhosis who received medical therapy alone. Among the 105 patients with cirrhosis, the median Society of Thoracic Surgeons score was 3.8% (1.5, 6.9), and the median Model for End‐Stage Liver Disease (MELD) score was 11.6 (9.4, 14.0). The TAVR group had similar in‐hospital (1.8% vs. 2.0%) and 30‐day mortality (3.6% vs. 4.2%) as the SAVR group. During the median follow‐up of 3.8 years (95% confidence interval, 3.0‐6.9), there were 63 (60%) deaths. MELD score (adjusted hazard ratio, 1.13; 95% confidence interval, 1.05‐1.21; P = 0.002) was an independent predictor of long‐term survival. In the subgroup of patients with MELD score &lt;12, the TAVR group had reduced survival compared with the SAVR group (median survival of 2.8 vs. 4.4 years; P = 0.047). However, in those with MELD score ≥12, survival after TAVR, SAVR, and medical therapy was similar (1.3 vs. 2.1 vs. 1.6 years, respectively; P = 0.53). Conclusion In select patients with cirrhosis, both TAVR and SAVR have acceptable and comparable short‐term outcomes. MELD score, but not Society of Thoracic Surgeons score, independently predicts long‐term survival after TAVR and SAVR. For patients with MELD score &lt;12, SAVR is a preferred procedure; however, neither procedure appears superior to medical therapy in patients with MELD score ≥12.
NutriRECS Consortium provides weak recommendations for continuing current red meat and processed meat consumption
Authors: Jackie West-Denning, Allan V. Prochazka
Journal: Annals of Internal Medicine (2020)

Source Citation Johnston BC, Zeraatkar D, Han MA, et al. Unprocessed red meat and processed meat consumption: dietary guideline recommendations from the Nutritional Recommendations (NutriRECS) Consortium. Ann Intern Med. 2019;171:756-64. 31569235
Open access epidemiological data from the COVID-19 outbreak
Authors: Bo Xu, Moritz U G Kraemer, Bo Xu, Bernardo Gutierrez, Sumiko Mekaru, Kara Sewalk, Alyssa Loskill, Lin Wang, Emily Cohn, Sarah Hill, Alexander Zarebski, Sabrina Li, Chieh-His Wu, Erin Hulland, Julia Morgan, Samuel Scarpino, John Brownstein, Oliver Pybus, David Pigott, Moritz Kraemer
Journal: The Lancet Infectious Diseases (2020)
The Impact of a Sweetened Beverage Tax on Beverage Volume Sold in Cook County, Illinois, and Its Border Area
Authors: Lisa M. Powell, Julien Leider, Pierre Thomas Léger
Journal: Annals of Internal Medicine (2020)

Sugar-sweetened beverage (SSB) consumption is linked to adverse health outcomes.To evaluate the impact of the 2017 Cook County, Illinois, Sweetened Beverage Tax (SBT) on the volume of taxed and untaxed beverages sold in Cook County and its 2-mile border area.Pre-post intervention-comparison site difference-in-differences study.Cook County, Illinois, and St. Louis City and County, Missouri, 2016 to 2017.Universal product code-level store scanner data from supermarkets and grocery, convenience, drug, mass merchandise, and dollar stores.Beverage volume sold of taxed and untaxed beverages, across product categories and sizes.Volume sold of taxed beverages decreased by 27% (ratio of incidence rate ratios [RIRR], 0.73 [95% CI, 0.70 to 0.75]) on average in Cook County relative to St. Louis during the 4 months that the SBT was in effect (compared with the same 4-month pretax period), with a net decrease of 21% after increases in volume sold in its border area (cross-border shopping) were taken into account. The magnitude of the decrease in volume sold across types of taxed beverages was heterogeneous: -32% (RIRR, 0.68 [CI, 0.65 to 0.72]) for soda versus -11% (RIRR, 0.89 [CI, 0.82 to 0.97]) for energy drinks, -37% (RIRR, 0.63 [CI, 0.59 to 0.66]) for artificially sweetened beverages versus -25% (RIRR, 0.75 [CI, 0.72 to 0.79]) for SSBs, and -29% (RIRR, 0.71 [CI, 0.68 to 0.74]) for family-size versus -19% (RIRR, 0.81 [CI, 0.79 to 0.84]) for individual-size beverages. There was no significant change in volume sold of untaxed beverages in Cook County or its border area.Data source did not allow for evaluation by store type or distance of outlets from the border.The Cook County SBT led to a substantial reduction in the volume sold of taxed beverages in Cook County. Part of this effect was offset by cross-border shopping. Cross-border shopping was limited to tax avoidance and did not extend to untaxed beverages.Bloomberg Philanthropies.
Genomic analysis for potential targetable mutations in relapsed and refractory germ cell tumors.
Authors: Sean Q. Kern, Lawrence H. Einhorn, Nabil Adra
Journal: Journal of Clinical Oncology (2020)

407 Background: A large number of metastatic germ cell tumors (GCTs) are cured with platinum-based chemotherapy. Patients that have relapsed or refractory disease can be cured with salvage therapy including salvage surgery, standard dose or high-dose chemotherapy with stem-cell transplant. However, 15-20% of patients with metastatic GCT are incurable with current therapeutic options. We sought to perform a genetic analysis on a cohort of these incurable patients to determine the presence of therapeutically targetable genetic mutations. Methods: After obtaining IRB approval, patients treated at Indiana University for refractory or relapsed GCT from 2016-2019 were analyzed with a next-generation sequencing (NGS) platform. Clinically relevant genomic alterations were reviewed to determine the potential for targeted therapies. Results: 10 patients with testicular (9) or ovarian (1) GCT underwent an analysis of tissue (7), blood (1), or both (2) with a mean 2.9 potential targetable mutations per patient. Four patients had NGS from preserved gonadal tissue removed prior to chemotherapy while 6/10 sample specimens were obtained post standard (1) or high-dose (5) chemotherapy. Potential known therapeutic targets were found in 80% (8/10). Of the platforms that tested biomarkers, high microsatellite instability (MSI) (1/5), intermediate tumor mutational burden (1/4), and high PD-L1 expression of 90% (1/3) was appreciated. The MSI-high patient did not respond to pembrolizumab. A patient with a KIT only mutation did not achieve a response to imatinib. One patient with KRAS, KIT, RAF1, CCND2, MET, AR, CDK6, PDGFRA, EGFR, and BRAF mutations was treated with brentuximab and was progression free for 2.5 months. Common mutations were CCND2 (4/10), RAF1 (2/10), KIT (2/10), and KRAS (2/10). Other mutations actionable in non-GCT tumors included ERCC1, TUBB3, RRMI, PIK3CA, TOPO1 and TP53. Conclusions: NGS identifies potential clinically relevant genomic alterations. Genetic mutations may enable future effective therapies as our understanding of platinum-resistant disease evolves. To our knowledge, this is among the first reports utilizing next-generation sequencing in GCT to direct potential therapeutic agents.
Raising alcohol tax to fund NHS would benefit poorer households, report claims
Authors: Elisabeth Mahase
Journal: BMJ (2020)

If an increase in the UK tax on alcohol went towards funding the NHS poorer households would see an overall benefit, a new report suggests.1

Researchers from the Institute of Alcohol Studies assessed whether an increase in alcohol tax would be regressive and would therefore “exacerbate inequalities.” They found “little difference between better off and worse off households” and said that, at worst, alcohol duty was only “mildly regressive.”

However, they said that three factors could mitigate how regressive any increase in alcohol duty proved to be. These were that poorer households might be more price sensitive, meaning that they would pay less of any increase in alcohol tax; that the revenue could be used to fund progressive government spending (for example, …
AK002, an Anti-Siglec-8 Antibody, Depletes Tissue Eosinophils and Improves Dysphagia Symptoms in Patients with Eosinophilic Esophagitis
Authors: Ikuo Hirano, Kathryn Peterson, Joseph Murray, Evan Dellon, Gary Falk, Nirmala Gonsalves, Mirna Chehade, John Leung, Robert Genta, Paneez Khoury, Adam Bledsoe, Camilla Shaw, Henrik Rasmussen, Bhupinder Singh, Alan Chang, Amol Kamboj, Marc Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2020)
The association of humoral antigen spread (AgS) with cytotoxic T lymphocyte (CTL) activity after sipuleucel-T (sip-T) treatment in two phase II clinical studies: STAMP and STRIDE.
Authors: Daniel Peter Petrylak, Emmanuel S. Antonarakis, Harini Kandadi, Lawrence Fong, Raymond S. Lance, Tuyen Vu, Nadeem Anwar Sheikh, Neal D. Shore, Charles G. Drake
Journal: Journal of Clinical Oncology (2020)

112 Background: Sip-T is an FDA-approved immunotherapy for metastatic castration-resistant prostate cancer. Sip-T generates CTL and humoral antigen activity, as measured by CD107a expression on PAP or PA2024 specific CD8+ T cells. These specific CTL activities were correlated with improved overall survival in several studies STAMP (NCT01487863) and STRIDE (NCT01981122) [1]. We examined whether CTL activity enables humoral response generation, hypothesizing that killing a target cell with immunotherapy releases antigens that generate a secondary antibody response, extending the effect. Methods: Using samples from patients who received sip-T in these studies, correlation between CTL activity and AgS responses to primary (PA2024, PAP) and secondary (PSA, LGALS3, LGALS8, KRAS, ERAS, KLK2) antibodies over time was assessed. Using R statistics software, a Wilcoxon signed rank test assessed differences across time (Wk, week: WK0, week 0, etc) and Spearman rank test for correlation between CTL activity and AgS responses. Results: In STAMP, PAP-specific CTL activity at WK0 was positively correlated with LGALS3 antibody responses at WK6, WK10, WK14 and WK26; likewise, PAP-specific CTL activity at WK6 was positively correlated with antibody response to PAP at WK0 (P = 0.035). In STRIDE, PAP-specific CTL activities at WK0 and both PAP- and PA2024-specific CTL activities at WK6 were positively correlated with LGALS8 antibody response at WK52. Plus, PAP- and PA2024- specific CTL activities at WK6 had significant, positive correlation with PA2024 antibody responses at WK0. In both, PA2024-specific CTL activity at WK26 was positively correlated with number of secondary antigen responses at WK10 and WK14. Conclusions: In all, PA2024-specific CTL activity at WK6 was positively correlated with antibody response to primary antigens (PA2024 and PAP) and 4 secondary antigens – PSA, KRAS, ERAS and KLK2 at multiple time points. In summary, treatment with sip-T in mCRPC appears to invoke the tumor immunity cycle, wherein tumor cell death releases compounds that act as secondary epitopes resulting in antigen spread. [1] DOI: 10.1158/1078-0432.CCR-18-0638. Clinical trial information: NCT01487863.
Acute interstitial nephritis (AIN) following immune checkpoint inhibitor (ICI) therapy in metastatic RCC (mRCC) as a potential predictor of response.
Authors: Viral M. Patel, Roy Elias, Joseph Formella, William Schwartzman, Alana Christie, Hans J. Hammers, James Brugarolas
Journal: Journal of Clinical Oncology (2020)

674 Background: ICIs such as nivolumab (N) have improved outcomes in mRCC patients (pts), but are also associated with immune-related adverse events. As has been shown in melanoma, we hypothesized that pts experiencing an autoimmune reaction directed against the tissue of origin may be more likely to benefit from ICI. Specifically, we evaluated whether pts with nivolumab-induced AIN (N-AIN) exhibited improved outcomes. Methods: We identified all patients with mRCC at UT Southwestern Medical Center from 2014 - 2018 who received at least one dose of N. We extracted creatinine (Cr) values over the entirety of each pt's N treatment course from the electronic medical record. Pts with a 1.5 fold Cr increase over baseline were investigated. The diagnosis of N-AIN was made by biopsy or by clinical criteria (timing of kidney injury, laboratory analysis, and exclusion of other causes). Results: We identified 177 mRCC pts who received at least one dose of N, 36 of whom had at least a 1.5 fold increase in Cr over baseline while on treatment. Of those, two had biopsy-proven AIN and one was clinically diagnosed, resulting in an incidence of 1.7%. Two received N monotherapy after first line, and the third in combination with ipilimumab as initial therapy. The earliest case of N-AIN occurred 1.5 months from N onset, and the others were diagnosed at 11 and 12 months. Of the 3 pts, one had a partial response lasting 2 years, and the other two had a complete response which is ongoing in both pts with over 2 years of follow up. In all 3 cases, N-AIN was treated with cessation of N and prednisone with a return to baseline kidney function. None required dialysis. Conclusions: AIN is a rare event with N, but it may portend a higher likelihood of response. One possible explanation is antigenic crossover between normal renal tubular cells and mRCC, resulting in a robust immune response.
Drug Approved for Rare Mutation in Gastrointestinal Tumor
Authors: Rebecca Voelker
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
Tolerance induction and microglial engraftment after fetal therapy without conditioning in mice with mucopolysaccharidosis type VII
Authors: Quoc-Hung Nguyen, Russell G. Witt, Bowen Wang, Carlo Eikani, Jeremy Shea, Lucas K. Smith, Gabrielle Boyle, Jaclyn Cadaoas, Renan Sper, John D. MacKenzie, Saul Villeda, Tippi C. MacKenzie
Journal: Science Translational Medicine (2020)

In utero therapy with recombinant enzyme or hematopoietic stem cells in MPS7 mice induces tolerance to missing enzyme and corrects brain microglia.
A Randomized Phase (PH) 2 Study with Exploratory Biomarker Analysis of Ficlatuzumab (F) A Humanized Hepatocyte Growth Factor (HGF) Inhibitory MAB in Combination with Gefitinib (G) Versus G in Asian Patients (PTS) with Lung Adenocarcinoma (LA)
Authors: T.S.K. Mok, K. Park, S.L. Geater, S. Agarwal, M. Han, M. Credi, K. McKee, N. Kuriyama, W. Slichenmyer, E.H. Tan
Journal: Annals of Oncology (2012)
Secular trends in incidence of type 1 and type 2 diabetes in Hong Kong: A retrospective cohort study
Authors: Andrea O. Y. Luk, Calvin Ke, Eric S. H. Lau, Hongjiang Wu, William Goggins, Ronald C. W. Ma, Elaine Chow, Alice P. S. Kong, Wing-Yee So, Juliana C. N. Chan
Journal: PLoS Medicine (2020)

There is very limited data on the time trend of diabetes incidence in Asia. Using population-level data, we report the secular trend of the incidence of type 1 and type 2 diabetes in Hong Kong between 2002 and 2015.The Hong Kong Diabetes Surveillance Database hosts clinical information on people with diabetes receiving care under the Hong Kong Hospital Authority, a statutory body that governs all public hospitals and clinics. Sex-specific incidence rates were standardised to the age structure of the World Health Organization population. Joinpoint regression analysis was used to describe incidence trends. A total of 562,022 cases of incident diabetes (type 1 diabetes [n = 2,426]: mean age at diagnosis is 32.5 years, 48.4% men; type 2 diabetes [n = 559,596]: mean age at diagnosis is 61.8 years, 51.9% men) were included. Among people aged <20 years, incidence of both type 1 and type 2 diabetes increased. For type 1 diabetes, the incidence increased from 3.5 (95% CI 2.2-4.9) to 5.3 (95% CI 3.4-7.1) per 100,000 person-years (average annual percentage change [AAPC] 3.6% [95% CI 0.2-7.1], p < 0.05) in boys and from 4.3 (95% CI 2.7-5.8) to 6.4 (95% CI 4.3-8.4) per 100,000 person-years (AAPC 4.7% [95% CI 1.7-7.7], p < 0.05] in girls; for type 2 diabetes, the incidence increased from 4.6 (95% CI 3.2-6.0) to 7.5 (95% CI 5.5-9.6) per 100,000 person-years (AAPC 5.9% [95% CI 3.4-8.5], p < 0.05) in boys and from 5.9 (95% CI 4.3-7.6) to 8.5 (95% CI 6.2-10.8) per 100,000 person-years (AAPC 4.8% [95% CI 2.7-7.0], p < 0.05) in girls. In people aged 20 to <40 years, incidence of type 1 diabetes remained stable, but incidence of type 2 diabetes increased over time from 75.4 (95% CI 70.1-80.7) to 110.8 (95% CI 104.1-117.5) per 100,000 person-years (AAPC 4.2% [95% CI 3.1-5.3], p < 0.05) in men and from 45.0 (95% CI 41.4-48.6) to 62.1 (95% CI 57.8-66.3) per 100,000 person-years (AAPC 3.3% [95% CI 2.3-4.2], p < 0.05) in women. In people aged 40 to <60 years, incidence of type 2 diabetes increased until 2011/2012 and then flattened. In people aged ≥60 years, incidence was stable in men and declined in women after 2011. No trend was identified in the incidence of type 1 diabetes in people aged ≥20 years. The present study is limited by its reliance on electronic medical records for identification of people with diabetes, which may result in incomplete capture of diabetes cases. The differentiation of type 1 and type 2 diabetes was based on an algorithm subject to potential misclassification.There was an increase in incidence of type 2 diabetes in people aged <40 years and stabilisation in people aged ≥40 years. Incidence of type 1 diabetes continued to climb in people aged <20 years but remained constant in other age groups.
Prevention and Management of Childhood Obesity and Its Psychological and Health Comorbidities
Authors: Justin D. Smith, Emily Fu, Marissa A. Kobayashi
Journal: Annual Review of Clinical Psychology (2020)

Childhood obesity has become a global pandemic in developed countries, leading to a host of medical conditions that contribute to increased morbidity and premature death. The causes of obesity in childhood and adolescence are complex and multifaceted, presenting researchers and clinicians with myriad challenges in preventing and managing the problem. This article reviews the state of the science for understanding the etiology of childhood obesity, the preventive interventions and treatment options for overweight and obesity, and the medical complications and co-occurring psychological conditions that result from excess adiposity, such as hypertension, nonalcoholic fatty liver disease, and depression. Interventions across the developmental span, varying risk levels, and service contexts (e.g.,community, school, home, health care systems) are reviewed. Future directions for research are offered with an emphasis on translational issues for taking evidence-based interventions to scale in a manner that will reduce the public health burden of the childhood obesity pandemic.
Cerebrospinal fluid analysis from bilateral external ventricular drains in suspected nosocomial infection
Authors: Kirsten R.I.S. Dorresteijn, Rolf J. Verheul, Gabriëlle A.E. Ponjee, Rishi Nandoe Tewarie, Marcella C.A. Müller, Diederik van de Beek, Matthijs C. Brouwer, Korné Jellema
Journal: Journal of Infection (2020)
Phase II randomized placebo-controlled neoadjuvant trial of nintedanib or placebo with gemcitabine and cisplatin in locally advanced muscle invasive bladder cancer (NEO-BLADE).
Authors: Syed A. Hussain, Jason Francis Lester, Richard Jackson, Matthew Gornall, Anthony Elliott, Simon J. Crabb, Robert A. Huddart, Naveen Vasudev, Alison Jane Birtle, Jane Worlding, Nicholas D. James, Omi Parikh, Maria Vilarino varela, Roberto Alonzi, Mark David Linch, Thomas Powles, Robert J. Jones
Journal: Journal of Clinical Oncology (2020)

438 Background: Neo-adjuvant chemotherapy Improves overall survival in patients with MIBC. Nintedanib is an orally available, potent, small molecule, triple kinase inhibitor with the potential to further benefit patient prognosis. Methods: NEO-BLADE was designed as a randomised, placebo controlled phase II study (n=120) to compare the addition of nintedanib (N) (150mg/200mg BD) to a combination of Gemcitabine (G) and Cisplatin (C). The study was powered (80%, alpha=15% [one sided]) to detect an improvement in the histological complete response rate of 20% (OR = 2.37). Results: 120 patients were recruited from 15 sites between 04/Dec/2014 and 03/Sep/2018 (22% Female) with 109 patients evaluable. Complete response (CR) rates ( by ITT) were 22/57 (38.6%) and 25/63 (39.7%) for patients treated with/without N. Pathological CR on ITT was 21/57 (36.8%) and 20/63 (31.74%); For pathological evaluable patients it was 21/41 (51. 22% ) and 20/45 ( 44.44%) respectively. Patients treated with N showed a benefit in terms of PFS and OS with 12 month PFS rates of 89.0% and 74.1% in the Nintedanib and Placebo group respectively. P= 0.038 and HR (CI) 0.479 (0.236, 0.976). OS at 12/24 months N 96.26%/ 88.87% while in Placebo group 82.83%,/69.36%. P=0.022, HR (CI) 0.389 (0.168, 0.902). Toxicity was reported in terms of grade 3 adverse events [12/63 (19%) Placebo, 23/57 (40%) N] and Serious Adverse Events [35/63 (56%) Placebo, 34/57 (53%) N]. In terms of thromboembolic events, this was observed in 16/57 (28%) of patients treated with N and 13/63 (21%) without N (P=0.461). Conclusions: The study failed to reach its primary endpoint in demonstrating an improvement in pathological response rate between N and Placebo when given alongside G and C. The trial met its secondary end point in improvement of progression free survival and over all survival at 12 months and 24 months. Safety data from this placebo -controlled study confirms triplets can be given safely. There are efficacy signals with improvement in PFS and OS and the regimen warrants further investigation in randomised phase III trial. Translational studies to assess bio markers of response are planned. Clinical trial information: 11977.
Allergen Specific Immunotherapy Leads To Multiple Transcriptional Changes In A Peach Allergy Mouse Model
Authors: Maria Rodriguez-Sanchez, Rafael Núñez, James Perkins, Alba Rodriguez-Nogales, Ana Molina Bueno, Maria Francisca Palomares Jerez, Francisco Rojo, Maria Torres Jaen, Cristobalina Mayorga
Journal: Journal of Allergy and Clinical Immunology (2020)