tbuckley/cabot-search huggingface dataset:
Ubiquitous antigen-specific T regulatory type 1 cells variably suppress hepatic and extrahepatic autoimmunity
Authors: Channakeshava Sokke Umeshappa, Jacques Mbongue, Santiswarup Singha, Saswat Mohapatra, Jun Yamanouchi, Justin A. Lee, Roopa Hebbandi Nanjundappa, Kun Shao, Urs Christen, Yang Yang, Kristofor K. Ellestad, Pere Santamaria
Journal: Journal of Clinical Investigation (2020)

Peptide MHC class II–based (pMHCII-based) nanomedicines trigger the formation of multicellular regulatory networks by reprogramming autoantigen-experienced CD4+ T cells into autoimmune disease–suppressing T regulatory type 1 (TR1) cells. We have shown that pMHCII-based nanomedicines displaying liver autoimmune disease–relevant yet ubiquitously expressed antigens can blunt various liver autoimmune disorders in a non–disease-specific manner without suppressing local or systemic immunity against infectious agents or cancer. Here, we show that such ubiquitous autoantigen-specific T cells are also awakened by extrahepatic tissue damage and that the corresponding TR1 progeny can suppress experimental autoimmune encephalomyelitis (EAE) and pancreatic β cell autoreactivity. In mice having EAE, nanomedicines displaying either ubiquitous or CNS-specific epitopes triggered the formation and expansion of cognate TR1 cells and their recruitment to the CNS-draining lymph nodes, sparing their liver-draining counterparts. Surprisingly, in mice having both liver autoimmunity and EAE, liver inflammation sequestered these ubiquitous or even CNS-specific TR1 cells away from the CNS, abrogating their antiencephalitogenic activity. In these mice, only the ubiquitous antigen-specific TR1 cells suppressed liver autoimmunity. Thus, the scope of antigen spreading in autoimmune disorders is larger than previously anticipated, involving specificities expected to be silenced by mechanisms of tolerance; the regulatory activity, but not the retention of autoreactive TR1 cells, requires local autoantigen expression.
Abstract P437: Early Insulin Resistance Responds To Lifestyle Interventions: The Premier Study
Authors: David P Cistola, Jamy D Ard, M. H Brenner, Alok K Dwivedi
Journal: Circulation (2020)

Introduction: Compensatory hyperinsulinemia (CH) is the metabolic response to early insulin resistance. Elevated blood insulin compensates for insulin resistance in tissues, maintaining normal fasting glucose and lipid levels. Therefore, CH is undetected by conventional screening tests for diabetes and cardiovascular risk. Our prior work showed that CH is prevalent in the U.S., especially in teenagers, young adults and Hispanic populations. Moreover, CH in young adults doubles the risk for diabetes later in life, independent of other known risk factors. The current study tested the hypothesis that markers of early insulin resistance improve with behavioral lifestyle interventions. Methods: The parent PREMIER study was a randomized controlled trial to evaluate the effect of lifestyle interventions on blood pressure. Many subjects also had insulin resistance, prediabetes (PreD) and/or metabolic syndrome (MetS). The interventions included increased physical activity, weight loss, reduced sodium and alcohol intake, and the DASH diet (Dietary Approaches to Stop Hypertension). A total of 810 subjects were randomized into three intervention arms: “established”, “established plus DASH” and “advice only”. Established refers to the above interventions, except for DASH. The subjects were 62% women and 34% African Americans; the mean age was 50.0±8.9 years. Inclusion criteria were age ≥25, elevated BP and BMI of 18.5-45.0 kg/m 2 . Exclusion criteria were diabetes, history of cardiovascular event, heart failure, cancer or psychiatric hospitalization within the last 2 years. Here, the analysis of covariance method was used to determine whether markers of insulin resistance at 6 months improved in the established or established plus DASH arms compared with the advice-only arm, after adjusting for baseline values. The results are reported as geometric means and 95% confidence intervals (CI). Results: Subjects in the lifestyle intervention arms showed reduced fasting insulin and increased insulin sensitivity compared with the advice-only arm. The mean fasting insulin levels after 6 months of the established and established plus DASH interventions were 9.8 μIU/mL (95% CI: 9.3, 10.3) and 10.1 (9.6, 10.7), respectively, compared with 12.0 (11.4, 12.6) for advice only. After excluding subjects with PreD and/or MetS at baseline, insulin levels for established and established plus DASH were 8.0 (7.3, 8.7) and 8.3 (7.3, 9.0), respectively, as compared with 9.8 (9.1, 10.6) for advice only. Likewise, HOMA2 %S increased to 101.2 (92.5, 110.6) and 93.3 (85.6, 101.8), respectively, compared with 79.0 (73.0, 85.5) in the advice-only arm. Conclusion: Markers of insulin resistance improved with the PREMIER lifestyle interventions, even in subjects who did not meet the clinical criteria for prediabetes or metabolic syndrome. Early screening and intervention may improve diabetes prevention outcomes.
Phase II study of S-1 as a first-line, S-1 plus cisplatin as a second-line, and weekly paclitaxel as a third-line therapy in patients with advanced gastric carcinoma
Authors: T. Yamada, Y. Rino, M. Kanari, H. Saeki, N. Yukawa, N. Wada, T. Ooshima, R. Yamada, C. Haruhiko, M. Masuda, T. Imada
Journal: Journal of Clinical Oncology (2007)

15186 Background: We conducted a pilot phase II study to evaluate the efficacy and safety of S-1 as a First-line, S-1 plus cisplatin as a second-line, and weekly paclitaxel as a third-line therapy for advanced gastric cancer. Patients and Methods: Between 2002 and 2005, 19 patients were enrolled into this study. Chemotherapy consisted of 60 mg/m 2 of S-1 for 4 weeks at 6 weeks interval, 60 mg/m 2 of S-1 for 3 weeks and 60mg/m 2 Cisplatin on day 8 at 5 weeks interval, and paclitaxel 60 mg/m 2 day 1, 8, 15 at 4 weeks interval. Results: The response rate was 15.8%, 7.7%, and 0% in the first-, second-, and third-line, respectively. The time to progression was 314 days. The mean survival time was 994 days. The median survival time was not calculated because 12 patients are still alive. With respect to hematological toxicity, the major adverse effect was leukopenia, which reached grades 3–4 in all line. And non-hematological toxicities, the major adverse effect was anorexia, which reached grade 3–4 in the Second line, and no deaths were attributable to the adverse effects of the drugs. Conclusion: This sequential therapy was very effective treatment for advanced gastric cancer with acceptable toxic side-effects. No significant financial relationships to disclose.
OUTCOMES FOLLOWING TRANSCATHETER TRANSSEPTAL VERSUS TRANSAPICAL MITRAL VALVE-IN-VALVE AND VALVE-IN-RING PROCEDURES
Authors: Salik Nazir, Sammy Elmariah, Saroj Lohani, Niranjan Tachamo, Muhammad Sohail Khan, Bidhya Timilsina, Faraz Khan Luni, Anthony Donato
Journal: Journal of the American College of Cardiology (2018)
Serum YKL-40 levels are usuful diagnostic tumor markers for adenocarcinoma of the uterine cervix
Authors: A. Mitsuhashi, H. Usui, H. Matsui, S. Tate, Y. Unno, K. Hirashiki, M. Shozu
Journal: Journal of Clinical Oncology (2007)

16008 Background: YKL-40 is secreted by cancer cells, macrophages, and neutrophils. It may be a growth factor, play a role in angiogenesis, or prevent apoptosis. The current study examined serum YKL-40 levels in patients with adenocarcinoma of the cervix to determine if it is a serum marker. Methods: The serum YKL-40 level was assayed by enzyme-linked immunosorbent assay in 24 patients with benign gynecologic disease, in 104 patients with squamous cell carcinonma , in 37 patietns with adenocarcinoma, and in 45 healthy controls, Serum squamous cell carcinoma antigen (SCC) and CA125 and CA19–9 values were obtained. Results: The serum YKL-40 level was higher in patients with cervical carcinoma than in the healthy controls (p&lt;0.0001). YKL-40 concentrations increased significantly in patients with squamous cell carcinoma and in those with adenocarcinoma (vs. normal control: p&lt;0.0001 and p&lt;0.0001, respectively). Judging from the receiver operating curves (ROC), the serum YKL-40 was more sensitive than other serum markers at identifying adenocarcinoma. In squamous cell carcinoma, this ability of serum YKL-40 was equal to that of SCC. YKL-40 was elevated in 68.4% of patients with stage I adenocarcinoma. The pretherapeutic serum level of YKL-40 correlated significantly with the International Federation of Gynecology and Obstetrics advanced stage in patients with adenocarcinoma of the cervix. Furthermore, the pretherapeutic serum level of YKL-40 correlated with disease persistence or recurrence. Conclusions: The serum YKL-40 level has potential usefulness as a diagnostic marker of adenocarcinoma of the cervix. [Table: see text] No significant financial relationships to disclose.
Deferasirox for myelodysplastic syndrome patients with transfusional iron overload: A budget impact analysis
Authors: N. Mody-Patel, S. L. Goldberg, V. Barghout
Journal: Journal of Clinical Oncology (2007)

17019 Background: Myelodysplastic syndromes (MDS) affect 12–20,000 in the US yearly. Blood transfusions, a mainstay of treatment, place MDS patients (pts) at risk for complications of transfusional iron overload (IO). Although recent data suggests iron accumulation significantly reduces survival in low and intermediate -1 risk MDS, incremental cost of adding chelators to health plan formularies are unknown. The economic impact of treating transfusional IO in MDS with two commercially available chelating agents were estimated from a health care plan (hcp) perspective. Methods: An Excel based model was developed to ascertain the incremental cost per treated MDS pt associated with oral deferasirox (DSX) relative to subcutaneous (sq) deferoxamine (DFO). Annual Per Member Per Month (PMPM) cost was calculated by dividing differences in annual expenditures for DSX and DFO by total plan membership. Data from published literature and pivotal clinical trials were used to estimate MDS prevalence and chelation eligibility. Costs associated with infusing sq DFO were based on medical claims analysis from 2001 to 2004. Medication costs were based on wholesale acquisition costs assuming 100% compliance. Sensitivity analyses were performed by varying model parameters. Results: A hcp of one million pts is estimated to have 119 pts with MDS, of which 22% are eligible for iron chelation therapy. The base-case model resulted in an incremental annual saving of $389.48 per treated MDS pt and an incremental budget impact of $0.0 PMPM of the hcp (function of relatively few MDS pts spread over million in hcp) associated with the use of DSX. Overall, 34.2% of DSX cost was offset by the absence of infusion costs, the key cost driver. Sensitivity analyses of varying pt weight and infusion costs showed the model results were robust. Conclusions: The annual budget impact of switching MDS patients with IO to DSX from DFO will potentially result in cost-savings for US health plans. These results should be considered in the selection of chelation therapy. No significant financial relationships to disclose.
Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study
Authors: David van Duin, Cesar A Arias, Lauren Komarow, Liang Chen, Blake M Hanson, Gregory Weston, Eric Cober, Omai B Garner, Jesse T Jacob, Michael J Satlin, Bettina C Fries, Julia Garcia-Diaz, Yohei Doi, Sorabh Dhar, Keith S Kaye, Michelle Earley, Andrea M Hujer, Kristine M Hujer, T Nicholas Domitrovic, William C Shropshire, An Dinh, Claudia Manca, Courtney L Luterbach, Minggui Wang, David L Paterson, Ritu Banerjee, Robin Patel, Scott Evans, Carol Hill, Rebekka Arias, Henry F Chambers, Vance G Fowler, Barry N Kreiswirth, Robert A Bonomo
Journal: The Lancet Infectious Diseases (2020)
A randomized phase II study of concomitant CT (docetaxel±cisplatin) and (RT) in first-line treatment of locally advanced head and neck cancer (LAHNC)
Authors: T. Bouillet, D. Nizri, A. Zawadi, D. Herman, D. Cupissol, H. Demaux, E. Touboul, J. Cretin, J. F. Morere
Journal: Journal of Clinical Oncology (2007)

6047 Background: 4 randomized trials demonstrated superiority of concomitant CT and radiotherapy (CRT) versus RT. Radiosensitizing effect of docetaxel showed in vitro, phase I recommended docetaxel dose as weekly 20 mg/m 2 with concomitant RT. Methods: (pts) with inoperable LAHNC (T3/T4); PS &lt; 2.RT in both arms was 70 Gy. In arm A, pts received 7 cycles of weekly Docetaxel 20 mg/m 2 before RT and cisplatin 20 mg/m 2 D1–3 every three weeks (3 cycles). In arm B, docetaxel alone at the same dose as in arm A.G-CSF secondary prophylaxis and ciprofloxacin recommended in both arms. Primary objective was WHO objective response rate (ORR). Statistical analysis: 2 steps according to a Simon plan authorized early interruption in case of insufficient efficacy. Results: 82 pts treated (Arms A/B:35/47); Arm A stopped in the first step. 47 pts treated in arm B. M/F (%) (83/17), median age 56.6 y, PS 0/1 (%) 54/46, T2/T3/T4 (%) 2/36/62, N0–1/N2/N3 (%) 30/55/15, primary site (%): buccal cavity (38), hypo-oropharynx (47), larynx (11). Median nbr of cycles 7 (3–7), 85% of pts completed planned CRT. ITT ORR: 89 % [75–96], median TTP 31.3 [19.3 –42.4], median OS 36.8 [21.2–49.5] months. Main grade 3–4 toxicities were mucositis (31.9%),skin toxicity (21.3%). Grade 3–4 hematological, GI and neurological toxicities were not observed. Conclusions: In this study, concomitant RT and weekly 20 mg/m 2 docetaxel is effective and well tolerated in LAHNC. The docetaxel/cisplatin arm was prematurely discontinued for insufficient efficacy. No significant financial relationships to disclose.
Abstract P466: Health and Healthcare Disparities in the Management of Systemic Hypertension and Cardiovascular Disease: The Critical Role of Insurance Status
Authors: Alexis K Okoh, Sherin Meledathu, Dara Jackson, Justin Gold, Christian Engell, Jose Bustillo, IM Residents
Journal: Circulation (2020)

Background: Minority populations are two to three times as likely to die of preventable cardiovascular events. Two main forces behind the challenge in managing hypertension among minority populations are disparities in health and healthcare. Aims: To identify the common health and healthcare disparities (HHD) among hypertensive patients who presented to a community medical center and propose a collaborative alliance for improvement. Methods: Internal medicine residents at the Newark Beth Israel Medical Center utilized a (P: Provider, I: Insurance, F: Food, E: Economic stability, N: Neighborhood, C: Culture and Language, E: Education, S: Social (PI-FENCES) model to identify health and health care disparities in hypertensive patients who presented to the ambulatory and inpatient settings over a 12-week-period. Demographic and baseline clinical characteristics were recorded. The distribution of each of the elements of PI-FENCES was documented and their association with respective demographics was determined. A protocol for usability study was designed based on preliminary data collected. Results: Between May 2019 and July 2019, a total of 86 hypertensive patients (mean ± SD age: 54 ± 12 years, BMI: 31± 8 kg/m 2 ) were identified. Seventy-one (83%) of them were African Americans. Of the patients identified, 51 (59%), presented to the ambulatory setting, 24 (28%) were seen in the in-patient setting and 11 (13%) were admitted to the Intensive care unit. According to the PI-FENCES model, distribution of HHD were as follows: n(%); P: 6 (6.9%), I: 40 (47%), F: 8(9.3%), E: 10 (11.6%), N: 1 (1.2%), C: 10 (14%), E: 26 (30.2%), S: 17 (19.7%). While 61 (71%) patients had at least 1 element of HHD, 9 (1.1%) had more than 2 elements of HHD. Associated cardiovascular conditions noted among admitted patients (n=35) were heart failure exacerbation (n=8) (22%) and cerebrovascular accident (n=4) (11%). Compared to patients with insurance, patients with no insurance were more likely to be admitted to the inpatient service or intensive care unit (Insurance: 31% vs. No insurance: 69%, p&lt;0.0001). Based on the preliminary data, a Reducing ReAdmission Secondary to Hypertension (RRaSH) proposal will be implemented. RRaSH will focus on developing follow-up and referral plans for all uninsured hypertensive patients who present to the in-patient setting. The program will also encourage free health screening of families and friends of this uninsured population. Conclusion: About one out of every two patients who presented with systemic hypertension to a community medical center had no insurance. Compared to patients with insurance, patients with no insurance were more likely to be admitted to the inpatient service or intensive care unit. RRaSH will be a follow-up and referral plan to help reduce readmissions secondary to hypertension.
Abstract MP65: Occupational Complexity and Childhood Socioeconomic Environment Influence Mid-to-Late-Life 20-year Change in Cognitive Function; The Atherosclerosis Risk in Communities (aric) Study
Authors: Anna Kucharska-newton, Priya Palta, Mehul D Patel, Laura Coker, Michelle L Meyer, Silvia Koton, Thomas Mosley, Gerardo M HEISS
Journal: Circulation (2020)

Background: We tested the hypothesis that lower childhood SES is associated with greater age-and disease-related cognitive decline. We further examined potential protective effects of high adulthood occupational complexity in the association of childhood SES with cognitive decline. Methods: Childhood neighborhood SES (child nSES) was ascertained at midlife among 12440 ARIC participants using retrospective historical county-level census-based measures of median household income, value of owner occupied housing units, percent of households receiving interest, dividend, or net rental income, educational attainment, and proportion of adults in professional, management, or executive occupations. An occupational complexity index (OCI) was derived from self-reported occupational categories at baseline. Cognitive function was assessed at ARIC visits 2 (1990-1993), 4 (1996-1998), and 5 (2011-2013) according to performance on tests of memory, executive function/processing speed and language. A composite global cognition z-score was estimated, with missing data imputed using multiple imputation by chained equations. Linear mixed effects models, adjusted for baseline age, sex, and race-study center, were used to examine the association of distribution-based tertiles of the child nSES summary score with baseline and 20-year change in cognitive function. We further examined interactions by OCI tertiles. Results: Global cognitive z scores in adulthood were persistently higher at baseline among participants with high (Visit 2 β =0.545 (95% CI 0.514, 0.576) as compared to intermediate (Visit 2 β=0.348 (95% CI 0.317, 0.381)) and low (Visit 2 β = 0.007 (95% CI -0.030, 0.044) child nSES. Participants with high,as compared to low, OCI, had higher baseline cognitive function across all tertiles of child nSES (Figure, p&lt;0.01). Conclusion: The positive association of child nSES with adult cognitive function is modified by adulthood occupational complexity. Child nSES is not associated with a 20-year cognitive change.
Abstract P360: Dietary Saturated Fats From Different Food Sources Show Inconsistent Associations With Various Indices of Diet Quality in the Canadian Population
Authors: Stephanie Harrison, Didier Brassard, Simone Lemieux, Benoit Lamarche
Journal: Circulation (2020)

Background: Canadian dietary guidelines include a recommendation to limit the consumption of foods high in saturated fats (SFA), regardless of their dietary source. The same guidelines also recommend consumption of lean red meat and low-fat dairy products. Yet, the association between the consumption of SFA from different food sources and diet quality is currently unknown. The objective of this study was to examine associations between SFA from various food sources and different indices of diet quality. Methods: Analyses are based on a sample of 11 106 respondents representative of Canadian adults (19-70 y) from the 2015 Canadian Community Health Survey (CCHS 2015). Dietary intakes and diet quality indices were calculated using a single interview-administered 24-hour recall. Food sources of SFA were classified according to the 2019 Canada’s Food Guide categories: 1) vegetables and whole fruits, 2) whole grain foods and 3) protein foods (including dairy and meat, among others). Foods not included in these three categories were grouped as All other foods . The 2010 alternative Healthy eating index (aHEI), the 2015 Healthy eating index (HEI-2015) and the 2007 Canadian Healthy eating index (C-HEI) were calculated. Due to the unreliability of data for trans-fat consumption in the CCHS 2015 database, the trans-fat subscore of the aHEI was removed from the original score. Results: While total SFA intake and SFA from All other foods were inversely correlated with all indices of diet quality (-0.55&lt;r&lt;-0.10, all p&lt;0.001), associations with SFA from dairy and meat were inconsistent. SFA from dairy were inversely correlated (p&lt;0.001) with the aHEI (r=-0.14) and the HEI-2015 (r=-0.16) but showed a weak positive correlation with the C-HEI (r=0.05, p&lt;0.001). SFA from meat were negatively correlated with the aHEI (r=-0.21, p&lt;0.001) and positively correlated with the C-HEI (r=0.11, p&lt;0.001). Removing subscores directly related to SFA intake in diet quality indices yielded positive correlations between SFA from dairy and the HEI-2015 (r=0.13, p&lt;0.001) and the C-HEI (r=0.19, p&lt;0.001). Conclusion: Consumption of SFA from different food sources are inconsistently associated with different indices of overall diet quality. Unsurprisingly, SFA from All other foods , which include low nutritive value foods, showed the strongest negative correlation with all diet quality scores. These results provide further support to the notion that guidance on SFA in future health policies should focus on food sources rather than on total intake of SFA.