tbuckley/cabot-search huggingface dataset:
Trends in Poor Health Indicators Among Black and Hispanic Middle-aged and Older Adults in the United States, 1999-2018
Authors: Michelle Odlum, Nathalie Moise, Ian M. Kronish, Peter Broadwell, Carmela Alcántara, Nicole J. Davis, Ying Kuen K. Cheung, Adler Perotte, Sunmoo Yoon
Journal: JAMA Network Open (2020)

Adults who belong to racial/ethnic minority groups are more likely than White adults to receive a diagnosis of chronic disease in the United States.To evaluate which health indicators have improved or become worse among Black and Hispanic middle-aged and older adults since the Minority Health and Health Disparities Research and Education Act of 2000.In this repeated cross-sectional study, a total of 4 856 326 records were extracted from the Behavioral Risk Factor Surveillance System from January 1999 through December 2018 of persons who self-identified as Black (non-Hispanic), Hispanic (non-White), or White and who were 45 years or older.The 1999 legislation to reduce racial/ethnic health disparities.Poor health indicators and disparities including major chronic diseases, physical inactivity, uninsured status, and overall poor health.Among the 4 856 326 participants (2 958 041 [60.9%] women; mean [SD] age, 60.4 [11.8] years), Black adults showed an overall decrease indicating improvement in uninsured status (β = -0.40%; P < .001) and physical inactivity (β = -0.29%; P < .001), while they showed an overall increase indicating deterioration in hypertension (β = 0.88%; P < .001), diabetes (β = 0.52%; P < .001), asthma (β = 0.25%; P < .001), and stroke (β = 0.15%; P < .001) during the last 20 years. The Black-White gap (ie, the change in β between groups) showed improvement (2 trend lines converging) in uninsured status (-0.20%; P < .001) and physical inactivity (-0.29%; P < .001), while the Black-White gap worsened (2 trend lines diverging) in diabetes (0.14%; P < .001), hypertension (0.15%; P < .001), coronary heart disease (0.07%; P < .001), stroke (0.07%; P < .001), and asthma (0.11%; P < .001). Hispanic adults showed improvement in physical inactivity (β = -0.28%; P = .02) and perceived poor health (β = -0.22%; P = .001), while they showed overall deterioration in hypertension (β = 0.79%; P < .001) and diabetes (β = 0.50%; P < .001). The Hispanic-White gap showed improvement in coronary heart disease (-0.15%; P < .001), stroke (-0.04%; P < .001), kidney disease (-0.06%; P < .001), asthma (-0.06%; P = .02), arthritis (-0.26%; P < .001), depression (-0.23%; P < .001), and physical inactivity (-0.10%; P = .001), while the Hispanic-White gap worsened in diabetes (0.15%; P < .001), hypertension (0.05%; P = .03), and uninsured status (0.09%; P < .001).This study suggests that Black-White disparities increased in diabetes, hypertension, and asthma, while Hispanic-White disparities remained in diabetes, hypertension, and uninsured status.
Abstract PO-060: Gna13 delays disease progression in mouse models of pancreatitis and pancreatic cancer
Authors: Mario A. Shields, Christina Spaulding, Mahmoud G. Khalafalla, Thao D.N. Pham, Hidayatullah G. Munshi
Journal: Cancer Research (2020)

Abstract We previously reported that Gα13 (Gna13), a member of the G12 heterotrimeric G proteins, is upregulated in pancreatic cancer patients and contributes to invasion in cancer cells in vitro. While other reports have demonstrated a tumor promoting function of Gα13 in solid tumors, Gα13 functions as a tumor suppressor in mouse models of B cell lymphoma. In this study, we evaluated the role of Gα13 in mouse models of pancreatitis and pancreatic cancer. To examine the role of Gα13 in pancreatic cancer development and progression, we crossed mice with a floxed allele of Gna13 to mice expressing oncogenic KrasG12D (KrasG12D;Pdx1-Cre). In parallel, we measured transplanted tumors established from pancreatic cell lines, where Gna13 is silenced or deleted. Further, we determined how loss of Gα13 influences cerulein-induced pancreatitis and inflammation-driven tumor progression in mice. Tumors derived from Gα13-deficient cells grew significantly slower than control cells when transplanted in either the orthotopic or subcutaneous site. However, cancer development and overall survival were unaffected in mice with heterozygous loss of Gα13, when compared to mice with intact expression of Gα13. Interestingly, in an aggressive cancer model (KrasG12D;P53R172H;Pdx1-Cre) loss of Gα13 led to faster tumor development and decreased overall survival. Furthermore, we found that Gα13 loss leads to enhanced inflammation and more progressive acinar-ductal metaplasia in pancreatitis. Overall, our results demonstrate a context-dependent role of Gα13 in the pancreas. Similar to previous reports, we show that inhibiting Gα13 in cancer cell lines limits tumor growth in vivo. However, in a genetic mouse model, loss of Gα13 promotes pancreatitis-induced inflammation and promotes tumor development and progression. Citation Format: Mario A. Shields, Christina Spaulding, Mahmoud G. Khalafalla, Thao D.N. Pham, Hidayatullah G. Munshi. Gna13 delays disease progression in mouse models of pancreatitis and pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-060.
Abstract 152: Cerebral Oximetry During Pediatric In-hospital Cardiac Arrest
Authors: Ivie D Esangbedo, Prakadeshwari Rajapreyar, Matthew Kirschen, Richard Hanna, Dana E Niles, Xuemei Zhang, Heather M Griffis, Conall Francoeur, Martin K Wakeham, Tara Petersen, Alexis A Topjian, Vinay M Nadkarni, Tia T Raymond
Journal: Circulation (2020)

Introduction: Cerebral near-infrared spectroscopy (NIRS) measuring regional oxygen saturation (rSO 2 ) during cardiopulmonary resuscitation (CPR) is associated with return of spontaneous circulation (ROSC) and survival to hospital discharge (SHD) in adults, with limited data in children. We hypothesized mean cerebral rSO 2 during pediatric in-hospital cardiac arrest (IHCA) would be associated with return of spontaneous circulation (ROSC). Methods: Consecutive case series of pediatric IHCA events with rSO 2 data reported between 2016-2020 by 3 sites to the Pediatric Resuscitation Quality (pediRES-Q) collaborative. We excluded patients with CPR duration ≤2 minutes or who had return of circulation via extracorporeal membrane oxygenation. We calculated mean rSO 2 for duration of CPR and the primary outcome measure was ROSC. Exploratory sensitivity analyses were performed for cutoffs of mean rSO 2 &gt;25, &gt;30, &gt;35, &gt;40 and &gt;50%. Analysis was done using independent samples t test, Exact logistic regression and Fisher’s exact test. Results: Of 36 events (26 index), median age was 3 [IQR 1,7.8] months; 29 (80.5%) had congenital heart disease and 15 (41.7%) had single ventricle (SV) physiology. Median CPR duration was 7.5 [IQR 3.8, 32.2] minutes and 28/36 (77.8%) had ROSC. Mean intra-arrest cerebral rSO 2 was 44.2% (±19.5) for ROSC vs. 37.4% (±15) for non-ROSC group ( p =0.267). Using Exact logistic regression, there was no association found between rSO 2 and ROSC, even after controlling for age, presence of congenital heart disease, and SV physiology. Using mean rSO 2 cutoffs &gt;25, &gt;30, &gt;35, &gt;40, and &gt;50%, we found no significant association with ROSC. We found same result in the SV subgroup. Conclusion: In this small pediatric cohort of predominantly cardiac patients, there was no significant association between cerebral rSO 2 during pediatric cardiac arrest and ROSC, even after controlling for important confounders of age and SV physiology. More extensive studies using larger populations, and evaluating intra-arrest change in cerebral rSO 2 from baseline, are warranted to provide more insight into the possibilities of using rSO 2 to guide CPR.
Estimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and meta-analysis
Authors: Mingjuan Tan, Ajeet S Bhadoria, Fuqiang Cui, Alex Tan, Judith Van Holten, Philippa Easterbrook, Nathan Ford, Qin Han, Ying Lu, Marc Bulterys, Yvan Hutin
Journal: The Lancet. Gastroenterology & hepatology (2020)

In 2016, of the estimated 257 million people living with chronic hepatitis B virus (HBV) infection worldwide, only a small proportion was diagnosed and treated. The insufficiency of information on the proportion of people infected with HBV who are eligible for treatment limits the interpretation of global treatment coverage. We aimed to estimate the proportion of people with chronic HBV infection who were eligible for antiviral treatment worldwide, based on the WHO 2015 guidelines.In this systematic review and meta-analysis, we searched Medline, EMBASE, and the Cochrane databases from Jan 1, 2007, to Jan 31, 2018, for studies describing HBsAg-positive people in the population or health-care facilities. We extracted information from published studies using a standardised form to estimate the frequency of cirrhosis, abnormal alanine aminotransferase (ALT), HBV DNA exceeding 2000 IU/mL or 20 000 IU/mL, presence of HBeAg, and eligibility for treatment as per WHO and other guidelines as reported in the studies. We pooled proportions through meta-analysis with random effects. The study was registered with PROSPERO, CRD42020132345.Of the 13 497 studies, 162 were eligible and included in our analysis. These studies included 145 789 participants. The pooled estimate of the proportion of cirrhosis was 9% (95% CI 8-10), ranging from 6% (4-8) in community settings to 10% (9-11) in clinic settings. Examining the proportion of participants who had characteristics used to determine eligibility in the WHO guidelines, 1750 (10·1%) of 17 394 had HBV DNA exceeding 20 000 IU/mL, and 20 425 (30·8%) of 66 235 had ALT above the upper limit of normal. 32 studies reported eligibility for treatment according to WHO or any other guidelines, with a pooled estimate of eligibility at 19% (95% CI 18-20), ranging from 12% (6-18) for studies in community settings to 25% (19-30) in clinic settings.Many studies described people with HBV infection, but few reported information in a way that allowed assessment of eligibility for treatment. Although about one in ten of the 257 million people with HBV infection (26 million) might be in urgent need of treatment because of cirrhosis, a larger proportion (12-25%) is eligible for treatment in accordance with different guidelines. Future studies describing people with HBV infection should report on treatment eligibility, according to broadly agreed definitions.WHO and US Centers for Disease Control and Prevention.
Abstract 14227: Timing Since Last Hospitalization for Heart Failure and Risks of Cardiovascular Death and Hospitalization of Heart Failure
Authors: Anna Norhammar, Johan Bodegard, Marcus Thuresson, Jan W Eriksson
Journal: Circulation (2020)

Introduction: Hospitalization for heart failure (hHF) is a serious event where approximately 10% die in hospital, 30-40% are readmitted within 1-year and with very poor 5-year survival rates. However, little is known about CV death or hHF risks immediately one year post discharge in a modern real-world clinical setting with access to modern HF-therapies. Hypothesis: To examine the risks of CV death and hHF in relation to timing since last hHF prior to follow-up in a prevalent HF population. Methods: Linked hospital-, prescribed drug- and cause of death registry data from Sweden was used, and hHF patients were identified by main diagnosis at an in-hospital admission. Index date was 1 st June 2018 and patients were grouped according to timing of hHF prior to index; &lt;4, 4-8, 8-26, 26-52 and &gt;52 weeks. Event rates were calculated per 100 patient years. Cox regressions adjusted for age, sex, ischemic heart disease, diabetes and chronic kidney disease were used to estimate risks. Results: Of 62,809 patients with a hHF; 2226 (4%), 1832 (3%), 5131 (8%), 6890 (11%) and 49,730 (74%) patients were allocated to the &lt;4, 4-8, 8-26, 26-52 and &gt;52 weeks groups respectively. The patient groups were similar, age 78 years, 44% women, 35% myocardial infarction but differences in CKD. Patients with the most recent hHF, &lt;4 weeks, had the highest hHF or CV death and hHF event rates compared to the other groups, 105 and 84 events per 100 patient years, respectively. Compared with patients with the least recent hHF (&gt;52 weeks), the risks of hHF or CV death and hHF were the highest in the group with the most recent hHF (&lt;4 weeks); HR 5.46 (95% CI 5.07-5.89) and 7.22 (95% CI 6.60-7.89). Conclusions: In this large hHF cohort, patients with the most recent hHF timing prior to follow-up had by far the highest risks of hHF or CV death and hHF compared to patients with less recent hHF timing. This supports an urgent and prompt need for effective treatment early after hospitalization for HF, with limited acceptance for treatment inertia.
Psoriasis Flares Following Systemic Glucocorticoid Exposure in Patients With a History of Psoriasis
Authors: Anna R. F. Gregoire, Britt K. DeRuyter, Erik J. Stratman
Journal: JAMA Dermatology (2020)

To our knowledge, this study is the first to assess the rate of any type of psoriasis flare during or immediately following the administration of systemic corticosteroids in patients with a known history of psoriasis.To determine the rates and types of psoriasis flares during or within 3 months after concluding systemic corticosteroid administration in adult patients with a known history of psoriasis.This retrospective cohort study assessed adult patients (≥18 years at the time of psoriasis diagnosis) evaluated in the Marshfield Clinic Health System (Marshfield, Wisconsin) with an established diagnosis of psoriasis and exposure to at least 1 systemic corticosteroid from October 31, 2012, to July 1, 2018. Exclusion criteria were patients younger than 18 years, patients with a diagnosis of psoriatic arthritis, and patients receiving only topical, intraarticular, or intrabursal corticosteroids.The primary outcome was rate of psoriasis flares during or within 3 months of discontinuation of the patient's first course of systemic corticosteroids. Secondary measures included rates of specific types of psoriasis flares, including pustular, erythrodermic, and worsening plaque stage psoriasis.Of 516 cohort patients, 288 (55.8%) were women, and the mean (SD) age at first psoriasis diagnosis was 49.6 (17.0) years. Among 1970 patients with a diagnosis of psoriasis before receiving systemic corticosteroids, a 1.42% (95% CI, 0.72%-2.44%) psoriasis flare rate of any type was identified when prescribed their first course of systemic corticosteroids. Further stratification identified only 1 severe flare (erythroderma) among all flares reported, with no pustular psoriasis flares identified (0.07%; 95% CI, 0.00%-0.26%).In this study, the rates of psoriasis flares were low, especially for severe psoriasis flares. Our results suggest that systemic steroids may be much less likely to trigger severe flares in patients with psoriasis than what is traditionally taught in dermatology.
Abstract 13730: Electrical Axes of P and T but Not QRS Waves on ECG Are New Indicators of Successfulness of the Nuss Operation for Pectus Excavatum Considering Anatomical Severity as Indicated by the Haller Index Acquired by CT
Authors: Nobusada FUNABASHI, Yoshio Kobayashi
Journal: Circulation (2020)

Introduction: Pectus excavatum (PEX) is a depression of the sternum which can physically constrict the heart and cause abnormal ECGs. The Nuss operation is a minimally invasive technique for PEX repair. Hypothesis: As right (RA) and left atria (LA) are compressed in PEX, axes of P, QRS, and T waves are abnormal and the Nuss operation normalizes them. We also took the Haller index (HI) into to account. Methods: 17 PEX patients (14 male, 12±6 years) underwent CT and ECG before and after the Nuss operation. Results: All Nuss operations were successful, and HI was significantly improved from 5.62±2.29 to 3.29±0.65 (P=0.0002). There were no significant differences before and after surgery for electrical axes of P waves (46±20 vs 65±55, P=0.20), and QRS waves (75±33 vs 76±23, P=0.72), but T waves were greater thereafter (22±27 vs 40±19, P=0.001). Correlation coefficients (CC) between the degree of axes of P, QRS and T waves, and HI before operation were -0.23, -0.06, and 0.11, respectively. These values after operation were -0.25, -0.06, and 0.19, respectively. As HI is an indirect indicator of heart compression, we evaluated the degree of RA and LA compression qualitatively as none, mild, and moderate/more. Of 17 patients, 5 had moderate/more compression of RA and/or LA by PEX (group 1); the remaining 12 did not show compression (group 2). Only P wave values were significantly smaller in group 1 than 2 before surgery, but these differences disappeared after surgery. In both groups, degree of axes of T waves was significantly greater after the operation. Conclusion: In patients with PEX, axes of T waves after the Nuss operation became significant greater than before the operation in patients with moderate or more compression of RA and/or LA by PEX. For P waves, this was smaller before the operation in those with compression but this was improved by the Nuss operation. P and T wave axes but not QRS could be therefore non-invasive indicators of Nuss operation success in addition to gross PEX appearance.
Pre-clinical Gene Therapy with AAV9/AGA in Aspartylglucosaminuria Mice Provides Evidence for Clinical Translation
Authors: Xin Chen, Sarah Snanoudj-Verber, Laura Pollard, Yuhui Hu, Sara S. Cathey, Ritva Tikkanen, Steven J. Gray
Journal: Molecular Therapy (2020)

Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disease caused by loss of the enzyme aspartylglucosaminidase (AGA), resulting in AGA substrate accumulation. AGU patients have a slow but progressive neurodegenerative disease course, for which there is no approved disease-modifying treatment. In this study, AAV9/AGA was administered to Aga−/− mice intravenously (i.v.) or intrathecally (i.t.), at a range of doses, either before or after disease pathology begins. At either treatment age, AAV9/AGA administration led to (1) dose dependently increased and sustained AGA activity in body fluids and tissues; (2) rapid, sustained, and dose-dependent elimination of AGA substrate in body fluids; (3) significantly rescued locomotor activity; (4) dose-dependent preservation of Purkinje neurons in the cerebellum; and (5) significantly reduced gliosis in the brain. Treated mice had no abnormal neurological phenotype and maintained body weight throughout the whole experiment to 18 months old. In summary, these results demonstrate that treatment of Aga−/− mice with AAV9/AGA is effective and safe, providing strong evidence that AAV9/AGA gene therapy should be considered for human translation. Further, we provide a direct comparison of the efficacy of an i.v. versus i.t. approach using AAV9, which should greatly inform the development of similar treatments for other related lysosomal storage diseases. Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disease caused by loss of the enzyme aspartylglucosaminidase (AGA), resulting in AGA substrate accumulation. AGU patients have a slow but progressive neurodegenerative disease course, for which there is no approved disease-modifying treatment. In this study, AAV9/AGA was administered to Aga−/− mice intravenously (i.v.) or intrathecally (i.t.), at a range of doses, either before or after disease pathology begins. At either treatment age, AAV9/AGA administration led to (1) dose dependently increased and sustained AGA activity in body fluids and tissues; (2) rapid, sustained, and dose-dependent elimination of AGA substrate in body fluids; (3) significantly rescued locomotor activity; (4) dose-dependent preservation of Purkinje neurons in the cerebellum; and (5) significantly reduced gliosis in the brain. Treated mice had no abnormal neurological phenotype and maintained body weight throughout the whole experiment to 18 months old. In summary, these results demonstrate that treatment of Aga−/− mice with AAV9/AGA is effective and safe, providing strong evidence that AAV9/AGA gene therapy should be considered for human translation. Further, we provide a direct comparison of the efficacy of an i.v. versus i.t. approach using AAV9, which should greatly inform the development of similar treatments for other related lysosomal storage diseases.
The miR-5694/AF9/Snail Axis Provides Metastatic Advantages and a Therapeutic Target in Basal-like Breast Cancer
Authors: Xin Tian, Hua Yu, Dong Li, Guojiang Jin, Shundong Dai, Pengchao Gong, Cuicui Kong, Xiongjun Wang
Journal: Molecular Therapy (2020)

Epigenetic deregulation, especially mutagenesis or the abnormal expression of epigenetic regulatory factors (ERFs), plays an important role in malignant tumorigenesis. To screen natural inhibitors of breast cancer metastasis, we adopted small interfering RNAs (siRNAs) to transiently knock down 591 ERF-coding genes in luminal breast cancer MCF-7 cells and found that depletion of AF9 significantly promoted MCF-7 cell invasion and migration. A mouse model of metastasis further confirmed the suppressive role of AF9 in breast cancer metastasis. RNA profiling revealed enrichment of AF9 targets genes in the epithelial-mesenchymal transition (EMT). Mechanistically, tandem mass spectrometry showed that AF9 interacts with Snail, which hampers Snail transcriptional activity in basal-like breast cancer (BLBC) cells. AF9 reconstitutes an activated state on the promoter of Snail, which is a master regulator of EMT, and derepresses genes by recruiting CBP or GCN5. Additionally, microRNA-5694 (miR-5694) targeted and degraded AF9 messenger RNA (mRNA) in BLBC cells, further enhancing cell invasion and migration. Notably, AF9 and miR-5694 expression in BLBC clinical samples correlated inversely. Hence, miR-5694 mediates downregulation of AF9 and provides metastatic advantages in BLBC. Restoring expression of the metastasis suppressor AF9 is a possible therapeutic strategy against metastatic breast cancer. Epigenetic deregulation, especially mutagenesis or the abnormal expression of epigenetic regulatory factors (ERFs), plays an important role in malignant tumorigenesis. To screen natural inhibitors of breast cancer metastasis, we adopted small interfering RNAs (siRNAs) to transiently knock down 591 ERF-coding genes in luminal breast cancer MCF-7 cells and found that depletion of AF9 significantly promoted MCF-7 cell invasion and migration. A mouse model of metastasis further confirmed the suppressive role of AF9 in breast cancer metastasis. RNA profiling revealed enrichment of AF9 targets genes in the epithelial-mesenchymal transition (EMT). Mechanistically, tandem mass spectrometry showed that AF9 interacts with Snail, which hampers Snail transcriptional activity in basal-like breast cancer (BLBC) cells. AF9 reconstitutes an activated state on the promoter of Snail, which is a master regulator of EMT, and derepresses genes by recruiting CBP or GCN5. Additionally, microRNA-5694 (miR-5694) targeted and degraded AF9 messenger RNA (mRNA) in BLBC cells, further enhancing cell invasion and migration. Notably, AF9 and miR-5694 expression in BLBC clinical samples correlated inversely. Hence, miR-5694 mediates downregulation of AF9 and provides metastatic advantages in BLBC. Restoring expression of the metastasis suppressor AF9 is a possible therapeutic strategy against metastatic breast cancer.