tbuckley/cabot-search huggingface dataset:
Long-term Intake of Gluten and Cognitive Function Among US Women
Authors: Yiqing Wang, Benjamin Lebwohl, Raaj Mehta, Yin Cao, Peter H. R. Green, Francine Grodstein, Manol Jovani, Paul Lochhead, Olivia I. Okereke, Laura Sampson, Walter C. Willett, Qi Sun, Andrew T. Chan
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Gluten avoidance has been suggested as having a benefit to cognitive health among the general population, given the link between gluten and cognitive impairment in patients with celiac disease. However, data are lacking in individuals without celiac disease. <h3>Objective</h3> To examine whether gluten intake is associated with cognitive function in women without celiac disease. <h3>Design, Setting, and Participants</h3> This cohort study included US women who participated in the longitudinal, population-based Nurses' Health Study II and had not previously or subsequently been diagnosed with celiac disease. Dietary data were collected from 1991 to 2015, and data on cognitive function were collected from 2014 to 2019. Data analysis was conducted from October 2020 to April 2021. <h3>Exposures</h3> Energy-adjusted gluten intake, cumulatively averaged across questionnaire cycles prior to cognitive assessment. <h3>Main Outcomes and Measures</h3> Three standardized cognitive scores assessed by the validated Cogstate Brief Battery: (1) psychomotor speed and attention score, (2) learning and working memory score, and (3) global cognition score. Higher scores indicated better performance. <h3>Results</h3> The cohort included 13 494 women (mean [SD] age, 60.6 [4.6] years). The mean (SD) gluten intake was 6.3 (1.6) g/d. After controlling for demographic and lifestyle risk factors in linear regression, no significant differences in standardized cognitive scores (mean [SD], 0 [1]) by quintile of gluten intake were found across highest and lowest quintiles of gluten intake (psychomotor speed and attention: −0.02; 95% CI, −0.07 to 0.03;<i>P</i>for trend = .22; learning and working memory: 0.02; 95% CI, −0.03 to 0.07;<i>P</i>for trend = .30; global cognition: −0.002; 95% CI, −0.05 to 0.05;<i>P</i>for trend = .78). The null associations persisted after additional adjustment for major sources of dietary gluten (ie, refined grains or whole grains), comparing decile categories of gluten intake, using gluten intake updated at each previous questionnaire cycle, or modeling changes in gluten intake. Similarly, these associations were not materially altered in sensitivity analyses that excluded women who had reported cancer or dementia diagnosis or had not completed all dietary assessments. <h3>Conclusions and Relevance</h3> In this study, long-term gluten intake was not associated with cognitive scores in middle-aged women without celiac disease. Our results do not support recommendations to restrict dietary gluten to maintain cognitive function in the absence of celiac disease or established gluten sensitivity.
Determinants of Response and Mechanisms of Resistance of CAR T-cell Therapy in Multiple Myeloma
Authors: Niels W.C.J. van de Donk, Maria Themeli, Saad Z. Usmani
Journal: Blood Cancer Discovery (2021)

BCMA-specific CAR T-cells have substantial therapeutic potential in multiple myeloma (MM), but most patients eventually relapse. Determinants of response and mechanisms of resistance are most likely multifactorial and include MM-related factors, premanufacturing T-cell characteristics, CAR T-cell-related features, and several components of the immunosuppressive microenvironment. Efforts to improve the potency and safety of CAR T-cell therapy include optimizing CAR design, combinatorial approaches to enhance persistence and activity, treatment of less heavily pretreated patients, and dual-antigen targeting to prevent antigen escape. We expect that these rationally designed strategies will contribute to further improvement in the clinical outcome of MM patients.
Efficacy and safety of a novel dosing strategy for ruxolitinib in the treatment of patients with myelofibrosis and anemia: the REALISE phase 2 study
Authors: Francisco Cervantes, David M. Ross, Atanas Radinoff, Francesca Palandri, Alexandr Myasnikov, Alessandro M. Vannucchi, Pierre Zachee, Heinz Gisslinger, Norio Komatsu, Lynda Foltz, Francesco Mannelli, Francesco Passamonti, Geralyn Gilotti, Islam Sadek, Ranjan Tiwari, Evren Zor, Haifa Kathrin Al-Ali
Journal: Leukemia (2021)

Abstract Anemia is a frequent manifestation of myelofibrosis (MF) and there is an unmet need for effective treatments in anemic MF patients. The REALISE phase 2 study (NCT02966353) evaluated the efficacy and safety of a novel ruxolitinib dosing strategy with a reduced starting dose with delayed up-titration in anemic MF patients. Fifty-one patients with primary MF (66.7%), post-essential thrombocythemia MF (21.6%), or post-polycythemia vera MF (11.8%) with palpable splenomegaly and hemoglobin &lt;10 g/dl were included. Median age was 67 (45–88) years, 41.2% were female, and 18% were transfusion-dependent. Patients received 10 mg ruxolitinib b.i.d. for the first 12 weeks, then up-titrations of up to 25 mg b.i.d. were permitted, based on efficacy and platelet counts. Overall, 70% of patients achieved a ≥50% reduction in palpable spleen length at any time during the study. The most frequent adverse events leading to dose interruption/adjustment were thrombocytopenia (17.6%) and anemia (11.8%). Patients who had a dose increase had greater spleen size and higher white blood cell counts at baseline. Median hemoglobin levels remained stable and transfusion requirements did not increase compared with baseline. These results reinforce the notion that it is unnecessary to delay or withhold ruxolitinib because of co-existent or treatment-emergent anemia.
Rarity of cutaneous findings among asymptomatic to mildly symptomatic patients with COVID‐19 admitted to a COVID care facility in Delhi, India: an observational study
Authors: A. Khurana, A. Mittal, R. Jain, A. Mishra, S.R. Mathachan
Journal: British Journal of Dermatology (2021)

In the peak of COVID-19 pandemic, a 500 bedded COVID care center was started by the Government of the National Capital Territory of Delhi, with support of a non-profit organization of medical doctors- Doctors for You1 .The aim of this was to provide isolation facility to asymptomatic or mildly symptomatic patients diagnosed with COVID-19. The center was monitored round the clock by a team of medical doctors. Facilities for oxygen administration and transfer to higher medical centers (Delhi government hospitals), in case of development of any severe signs/symptoms(SpO2 < 95% on room air or < 90% after supplementing with 100% oxygen),were available. X ray facility was not available at the centre.
Seroprevalence of anti-SARS-CoV-2 antibodies in Iquitos, Peru in July and August, 2020: a population-based study
Authors: Carlos Álvarez-Antonio, Graciela Meza-Sánchez, Carlos Calampa, Wilma Casanova, Cristiam Carey, Freddy Alava, Hugo Rodríguez-Ferrucci, Antonio M Quispe
Journal: The Lancet Global Health (2021)
Abstract 14759: Burden of Intracranial Hemorrhage in Patients With Acute Myocardial Infarction in the United States, 2000-2017
Authors: Sri Harsha Patlolla, Saraschandra Vallabhajosyula
Journal: Circulation (2020)

Introduction: There is a paucity of contemporary data on the burden of intracranial hemorrhage (ICH) complicating acute myocardial infarction (AMI). Methods: The National Inpatient Sample database (2000 to 2017) was used to evaluate in-hospital burden of ICH in adult (&gt;18 years) AMI admissions. In-hospital mortality, hospitalization costs, length of stay, and measure of functional ability were the outcomes of interest. The discharge destination along with use of tracheostomy and percutaneous endoscopic gastrostomy (PEG) were used to estimate functional burden. Results: Of a total 11,622,528 AMI admissions, 23,422 (0.2%) had concomitant ICH. Compared to those without, admissions with ICH were on average older, female, of non-White race, with greater comorbidities, and higher rates of arrhythmias (all p&lt;0.001). Female sex, non-White race, ST-segment-elevation AMI presentation, use of fibrinolytics, mechanical circulatory support and invasive mechanical ventilation were identified as individual predictors of ICH. The AMI admissions with ICH received less frequent coronary angiography (46.9% vs. 63.8%), percutaneous coronary intervention (22.7% vs. 41.8%), and coronary artery bypass grafting (5.4% vs. 9.2%) as compared to those without (all p&lt;0.001). ICH was associated with a significantly higher in-hospital mortality (41.4% vs. 6.1%; adjusted OR 5.65 [95% CI 5.47-5.84]; p&lt;0.001), and adjusted temporal trends showed a steady decrease in in-hospital mortality over the 18-year period (Figure 1A). AMI-ICH admissions also had longer hospital length of stay, higher hospitalization costs, and greater use of PEG (all p&lt;0.001). In AMI-ICH survivors (N=13, 689), 81.3% had a poor functional outcome indicating severe morbidity and temporal trends revealed a slight increase over the study period (Figure 1B). Conclusions: ICH causes a substantial burden in AMI due to associated higher in-hospital mortality, resource utilization, and poor functional outcomes.
1O Detection of homologous recombination repair deficiency (HRD) in treatment-naive early triple-negative breast cancer (TNBC) by RAD51 foci and comparison with DNA-based tests
Authors: V. Serra Elizalde, A. Llop-Guevara, A. Pearson, C. Cruz, M. Castroviejo-Bermejo, N. Chopra, H. Tovey, C. Toms, D. Kriplani, H. Gevensleben, R. Roylance, S. Chan, A. Tutt, A. Skene, A. Evans, H.R. Davies, J. Bliss, S. Nik-Zainal, J. Balmaña, N. Turner
Journal: Annals of Oncology (2021)
Abstract 16212: Ultrasound Jugular Venous Pulsation Outperforms Visual Assessment and Ivc Collapsibility for Central Venous Pressures in Obese Patients
Authors: Libo Wang, Jonathan Harrison, Elizabeth Dranow, Lillian KHOR
Journal: Circulation (2020)

Introduction: Accurate volume status assessment is central to heart failure management, but current non-invasive bedside techniques remain a challenge, particularly in obese patients. Studies have shown variability and inaccuracy of the jugular venous pulse (JVP) exam in estimating right atrial pressure (RAP). Hypothesis: The accuracy of POCUS imaging of the JVP (uJVP) is preserved in obesity. Methods: Prior to undergoing right heart catheterization (RHC), subjects were enrolled for internal jugular vein imaging with a POCUS device, Butterfly iQ™. The vJVP was identified by traditional examination technique along with pIVC (an IVC&gt;2.1 cm and &lt;50% collapsible was considered greater or equal to 10mmHg in RAP). The IJV was identified by POCUS with the patient reclined (head of bed between 30-45°) and followed cranially until tapering smaller than the adjacent carotid artery throughout the entirety of the respiratory cycle. The height of this collapse point from the sternal angle added to 5 centimeters was defined as uJVP. Results: 41 participants, 24 of whom were obese (BMI &gt; 30 kg/m2), underwent vJVP, pIVC diameter, and uJVP assessments prior to RHC. The receiver operator curve (ROC) or Area under the Curve (AUC) was robust for uJVP and did not significantly differ between non-obese and obese participants (AUC=0.923 and AUC=0.852 respectively) in predicting RAP &gt;=10mmHg. AUC decreased significantly with obesity for vJVP. The AUC was modest for pIVC in the non-obese, but performed poorly in obesity (Figure 1B, 1C). Conclusions: This is the first comparative study of bedside, non-invasive methods of volume assessment. The accuracy of vJVP and pIVC deteriorated with obesity, whereas the uJVP, maintained good predictive value irrespective of obesity. The novel uJVP is a promising bed-side tool for volume assessment in the obesity and warrants further study.
Abstract 16161: Severe Left Ventricular Dilation at Initial Heart Failure Presentation: Recovery, Outcomes and Mortality
Authors: Nathan Kong, Daniel Gold, John Blair, Neal K Bhatia, Divya Gupta, Anand Shah
Journal: Circulation (2020)

Introduction: Guideline directed medical therapy (GDMT) can result in improvement in left ventricular (LV) size and function following heart failure with reduced ejection fraction (HFrEF) diagnosis. Some therapies, such as device based interventions, are thus delayed in hopes of achieving recovery. We report remodeling and clinical outcomes in a large, consecutive series of patients presenting with a severely dilated and dysfunctional LV following 3-6 months of initial GDMT. Hypothesis: Patients with HFrEF and LVEDD ≥ 6.5cm at initial diagnosis will have a low likelihood of myocardial recovery in 3-9 months and a high burden of associated morbidity and mortality. Methods: Patients were retrospectively identified by a database search of echocardiogram studies obtained at Emory Healthcare hospitals between 2008-2018. Chart review was done to select patients’ with a new diagnosis of HFrEF and LVEDD ≥ 6.5 cm. Myocardial recovery was defined as LVEF &gt; 35% at a follow-up echocardiogram done at least 3 months after initial study. Primary endpoint for Kaplan-Meier survival analysis was freedom from composite of death, enrollment in hospice, left ventricular assist device, or cardiac transplantation. Results: 339 patients with a median follow-up of 3.4 years were identified. The mean age was 49.0 ± 14.9 year and 68 (20.1%) were female. The mean LVEF at diagnosis was 16.9 ± 7.9% with a mean LVEDD of 7.0 ± 0.4 cm. Median time to repeat echocardiogram was 6.0 months. LVEF at follow-up was 18.3 ± 8.8% with a mean LVEDD of 6.9 ± 0.6 cm. Only 8 (2.5%) patients had myocardial recovery. 1- and 5-year primary event survival was 82.4% and 55.4% respectively. The median event free time was 5.9 years. Conclusions: Patients with de novo diagnosis of HFrEF and moderate or severe left ventricular enlargement have very low rates of myocardial recovery. Low survival estimate at 5 years suggests a potential benefit for early consideration of advanced therapies and device based therapies in this cohort.
The Relationship between Resting Heart Rate and Peak VO2: A Comparison of Atrial Fibrillation and Sinus Rhythm
Authors: Kato Yuko, Suzuki Shinya, Uejima Tokuhisa, Han Ning, Senba Hiroaki, Kanoh Hiroto, Matsuno Shunsuke, Takai Hideaki, Otsuka Takayuki, Oikawa Yuji, Nagashima Kazuyuki, Kirigaya Hajime, Sagara Koichi, Kunihara Takashi, Yajima Junji, Sawada Hitoshi, Aizawa Tadanori, Yamashita Takeshi
Journal: Circulation (2016)
Bringing Harm Reduction into Health Policy — Combating the Overdose Crisis
Authors: Kimberly L. Sue, David A. Fiellin
Journal: New England Journal of Medicine (2021)

Interview with Dr. Kimberly Sue on federal health policy surrounding harm-reduction approaches to substance use. (07:40)Download In the face of increasing drug-related morbidity and mortality, the Biden administration could signal a change in federal strategy by fully endorsing harm reduction as a valid, evidence-based policy to improve the health of people who use drugs.
Hepatitis A outbreak associated with consumption of dates, England and Wales, January 2021 to April 2021
Authors: Tatiana Garcia Vilaplana, David Leeman, Koye Balogun, Siew Lin Ngui, Emily Phipps, Wazirzada M Khan, Sooria Balasegaram
Journal: Eurosurveillance (2021)

We report a national hepatitis A virus (HAV) outbreak linked to the consumption of Medjool dates. Twenty-nine cases of three genetically related sequences have been identified. Epidemiological investigations identified a suspected product (adjusted odds ratio: 47.36; 95% confidence interval: 1.79-1,256.07; p = 0.021). Microbiological testing has confirmed the presence of HAV on dates recovered from two cases and the product has been recalled. Date consumption is currently likely to be increased in connection with Ramadan, with potential ongoing contamination risk.
Comment on Piccinini and Bergman. The Measurement of Insulin Clearance. Diabetes Care 2020;43:2296–2302
Authors: Amalia Gastaldelli, Ralph A. DeFronzo, Marzieh Salehi
Journal: Diabetes Care (2020)

We read with interest the review by Piccinini and Bergman (1) that 1 ) argues for superiority of the Polidori-Bergman model or peripheral-portal infusion technique to estimate the metabolic clearance rate of insulin (MCR-I) over other methods, and 2 ) hypothesizes that reduced MCR-I causes type 2 diabetes (T2D).

Obviously, the peripheral-portal infusion approach is not feasible in humans.

The Polidori-Bergman model allows one to estimate the MCR-I contribution of the liver and peripheral tissues. For reasons outlined below, we believe that some of the assumptions and constraints of this model adversely affect the accuracy of MCR-I estimation, especially during the fed state, such as an oral glucose tolerance test (OGTT).

The Polidori-Bergman model assumes that hepatic insulin extraction (HIE) is either constant or saturable, whereas …
SIRT3 overexpression and epigenetic silencing of catalase regulate ROS accumulation in CLL cells activating AXL signaling axis
Authors: Guru P. Maiti, Sutapa Sinha, Hasan Mahmud, Justin Boysen, Mariana T. Mendez, Sara K. Vesely, Jennifer Holter-Chakrabarty, Neil E. Kay, Asish K. Ghosh
Journal: Blood Cancer Journal (2021)

Mitochondrial metabolism is the key source for abundant ROS in chronic lymphocytic leukemia (CLL) cells. Here, we detected significantly lower superoxide anion (O2-) levels with increased accumulation of hydrogen peroxide (H2O2) in CLL cells vs. normal B-cells. Further analysis indicated that mitochondrial superoxide dismutase (SOD)2, which converts O2- into H2O2 remained deacetylated in CLL cells due to SIRT3 overexpression resulting its constitutive activation. In addition, catalase expression was also reduced in CLL cells suggesting impairment of H2O2-conversion into water and O2 which may cause H2O2-accumulation. Importantly, we identified two CpG-islands in the catalase promoter and discovered that while the distal CpG-island (-3619 to -3765) remained methylated in both normal B-cells and CLL cells, variable degrees of methylation were discernible in the proximal CpG-island (-174 to -332) only in CLL cells. Finally, treatment of CLL cells with a demethylating agent increased catalase mRNA levels. Functionally, ROS accumulation in CLL cells activated the AXL survival axis while upregulated SIRT3, suggesting that CLL cells rapidly remove highly reactive O2- to avoid its cytotoxic effect but maintain increased H2O2-level to promote cell survival. Therefore, abrogation of aberrantly activated cell survival pathways using antioxidants can be an effective intervention in CLL therapy in combination with conventional agents.
21P BACH1 and HIF1α predict response to neoadjuvant nab-paclitaxel (nP) treatment in early breast cancer (BC)
Authors: V. Vladimirova, A. Schneeweiss, C. Jackisch, K.E. Weber, C. Denkert, S. Schmatloch, T. Karn, P.A. Fasching, S. Braun, C. Szeto, B. Sinn, M. van Mackelenbergh, C. Schem, E. Stickeler, P. Soon-Shiong, F. Marmé, V. Mueller, M. Untch, V. Nekljudova, S. Loibl
Journal: Annals of Oncology (2021)
80P Radiolabelled trastuzumab Fab as a theranostic molecule for HER2 positive breast cancers
Authors: Y. Rathore, J. Shukla, B.R. Mittal, G. Singh, K. Gopal, R. Kumar, A. Bal, I. Laroiya, T. Lakhanpal
Journal: Annals of Oncology (2021)
Lck Is a Crucial Anergy Regulator in CLL
Authors: Alexander Fuchs, Melanie Märklin, Jonas Heitmann, Felicia Truckenmüller, Sebastian Jonas Saur, Manuela Ganser, Stefanie Bugl, Ursula Kohlhofer, Leticia Quintanilla-Martinez, Hans-Georg Kopp, Lothar Kanz, Anjana Rao, Stefan Wirths, Martin R. Mueller
Journal: Blood (2017)
Abstract 17352: Seasonal Trends of Acute Idiopathic Pericardial Effusion Requiring Pericardial Drainage
Authors: Muhammad M Furqan, Abdullah Yesilyaprak, Beni R Verma, Hassan Mehmood Lak, Dakshin Gangadharamurthy, Muzna Hussain, Patrick H Collier, Allan L Klein
Journal: Circulation (2020)

Background: The seasonal trends of idiopathic pericardial effusion (PEff) are not known. Small PEff is usually asymptomatic but moderate to large PEff may lead to cardiac tamponade necessitating pericardial drainage procedures. Seasonal variations of PEff can help identify the association with viral infections that follow a seasonal pattern. Therefore, we sought to characterize the seasonal trends of moderate to large PEff. Methods: We retrospectively identified pericardial effusion patients from January 2015 to December 2019. Moderate to large PEff was defined as PEff requiring either pericardiocentesis or pericardial window. Patients with minimal to small PEff, autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis), cardiac surgeries/invasive procedures, hemopericardium, chronic pericarditis, malignancy, and metastasis were excluded. Data was acquired from electronic medical records and frequencies, means, percentages, and chi-square test statistics were calculated. Results: Of the 472 patients with PEff, 63% (n=296) were males and 37% (n=176) females. The median age was 61 years. Pericardiocentesis was performed in 65% of patients and 35% had pericardial window. All seasons had similar incidence of PEff (winter 27%, spring 25%, summer 24%, fall 23%, [X 2 =1.81, p=0.612]). The incidence also remained same across all the quarters of the year (Q1 25%, Q2 25%, Q3 26%, Q4 24%, [X2=0.119, p=0.990). The incidence of pericardiocentesis and pericardial window in winter (27% vs 27.5), Spring (22% vs 31%), summer (26% vs 20%), fall (25% vs 20%) showed no difference (X2=6.40, p=0.094). Conclusion: The incidence of moderate to large acute idiopathic pericardial effusion is consistent across all seasons and quarters. Similarly, no significant seasonality was associated with pericardiocentesis and pericardial window procedures.
Abstract 16673: Empowering Heart Failure Patients Through Technology and Focused Education
Authors: Jacob Chemmalakuzhy, Martin Berk, Sandeep Kamath, Allison Roberts, Gregory Duck, Lindsay Beeker, Kristi Esposito, Cherie Boxberger, Jacqueline Tomei, Steven Redfearn, Michelle Scharnott, Adele Santana, Remy Poudel
Journal: Circulation (2020)

Introduction: Heart Failure (HF) patient engagement after hospital discharge is key to preventing readmission and compliance. According to Medicare Hospital Compare the average rate of unplanned readmission is 21.6% Objective: The Rise Above Heart Failure™(RAHF) pilot program was created to identify strategies to reduce the burden of common HF complications and ultimately reduce hospitalization. The pilot included targeted quality improvement strategies, provider engagement, and a redesigned patient journey. Methods: Three North Texas pilot sites received quality improvement consultation and measured their progress towards improved guideline-directed care by tracking the impact to the 1,347 patients discharged with heart failure in Get With The Guidelines®-Heart Failure (GWTG-HF). The RAHF Pilot Program focused on engaging key stakeholders who working in partnership with AHA staff, developed a new patient journey for patients in the pilot. Results: The percent of HF patients who received 60 minutes of heart failure education by a qualified heart failure educator was analyzed and yielded the following results: the program hospitals saw an average adherence of 51.0% in Q2 and 53.9% adherence in Q4 (%Δ =5.8%). Additionally, the pilot program’s average of 50.47% during Q2-Q4 was more than 10% greater than the national average during the same time period. In the outpatient setting, HF PATH app users completed both a pre and post knowledge assessment between Oct 2019 - March 2020. A perfect score on the assessment is 19. The average pre-score for these participants is 16.33, while the average post-score for these participants is 17. Conclusions: Midterm results indicate that the program is successfully increasing HF patient education to increase patient awareness and understanding of HF, as represented by higher adherence to the 60 Minutes of Heart Failure Education measure and positive trends in the HF Path app knowledge assessment scores.