tbuckley/cabot-search huggingface dataset:
COPD phenotypes by computed tomography and ventilatory response to exercise
Authors: S. Rodrigues Sousa, J. Nunes Caldeira, C. Rodrigues
Journal: Pulmonology (2022)

Computed tomographic (CT) phenotypic patterns of chronic obstructive pulmonary disease (COPD) identify different clinical features of disease. The impact of these variables on the physiological response to exercise has been the focus of a great deal of research as it allows more individualized clinical approaches. The aim of our study was to evaluate the relationships between CT phenotyping of subjects with COPD and the ventilatory response during cardiopulmonary exercise testing (CPET). Subjects with COPD were classified into four phenotypes based on CT metrics of emphysema (low attenuation area less than a threshold of -950 Hounsfield [%LAA-950]) and airwall thickness (bronchial wall area percentage [%WA]). Eighty COPD patients (78.8% males, median age 65±11.3 years) were enrolled in the study. Based on CT phenotype, 25 (31.3%) patients were classified as normal, 27 (33.8%) air dominant, 17 (21.3%) emphysema dominant and 11 (13.8%) mixed type. The emphysema and mixed phenotypes showed the highest ventilatory equivalent for carbon dioxide (VE/VCO2) and VE/VCO2 slope (p<0,05). In all phenotypes, %LAA was positive correlated with VE/VCO2 and VE/VCO2 slope (r = 0.437, p = 0.006 and r = 0.503, p<0.001, respectively). %WA also showed a positive correlation with VE/VCO2 and VE/VCO2 slope (r = 0.541, p<0.001 and r = 0.299, p = 0.033, respectively). In multivariate regression models, after adjustment for age, BMI, sex and FEV1, %LAA was the only independent predictor of VE/VCO2 and VE/VCO2 slope (β 0.343, SE 0.147, 95% CI 0.009/0.610, p = 0.044 and β 0.496, SE 0.081, 95% CI 0.130/0.455, p = 0.001, respectively). Emphysema (%LAA) and airways metrics (%WA) had strong relationships with the different characteristics of ventilatory response to exercise in subjects with mild to moderate COPD. In particular, %LAA seemed to play an important role as an independent predictor of VE/VCO2 and VE/VCO2 slope. These results suggested that CT phenotyping may help predicting ventilatory response to exercise in subjects with COPD.
Abstract 077: Association Between Key Family And Individual Factors And The Risk Of Obesity In Offspring: Findings From A Prospective Cohort Study
Authors: Liang Wang, Diana Morelen, Arsham Alamian
Journal: Circulation (2022)

Purpose: There remains a significant gap in our knowledge of the synergistic nature of family dynamics, child characteristics, and child-rearing features in the etiology of obesity from childhood through adolescence. We assessed the impact of family dynamics (poverty, family structure), child characteristics (child temperament), and child-rearing features (maternal depression, maternal sensitivity, and type of child care) on the development of childhood obesity. Methods: Children (n=1,240) whose weights and heights were measured at least once for ten time points (from 2 years through 15 years) from the NICHD Study of Early Child Care and Youth Development were included. Childhood obesity was based on standardized height and weight measures taken during the interviews and was defined according to appropriate 2000 CDC age and sex-specific body mass index percentiles. Maternal sensitivity was based on behavioral observations when children were 6 months of age, and all other measures were parental self-report. Generalized estimating equation (GEE) was used to examine the impact of family and individual factors on the childhood obesity after adjusting for covariates (child sex, race, birth weight). Results: Prevalence of obesity increased from 2 years (5.6%) to school ages (e.g., 19.5% at Grade 5 and 15.5% at age 15 years). Adjusted GEE models showed that living below poverty level was associated with an increased risk of obesity (odds ratio (OR)=1.62, 95% Confidence Interval (CI)=1.05, 2.53). Additionally, being nonwhite and higher birthweight were positively associated with an increased risk of obesity across time. Conclusion: Among these key family and individual factors, poverty status was observed to be the strongest predictor of obesity risk of offspring across time. Findings highlight the importance of systemic-level public health changes in obesity reduction efforts and suggest that poverty-reduction based prevention and intervention are likely more effective targets than more individual/family specific targets.
123P Clinical and environment factors impacting malignant pleural mesothelioma prognosis
Authors: N.O.T. Deboever, D. McGrail, N. Zhou, M. Altan, J. Olivia, E. Parra, J. Zhang, P. Lee, R. Rajaram, W. Hofstetter, A. Vaporciyan, R. Mehran, D. Rice, K. Tomczak, A. Weissferdt, A. Tsao, C. Haymaker, B. Sepesi
Journal: Annals of Oncology (2022)
Abstract P113: Increasing Fruit And Vegetable Intake Prevents Incident Cardiovascular Disease And Cardiovascular Deaths
Authors: Azuka Atum, Susan Hennessy, Joanne Penko, Pamela Coxson, Pengxiao Wei, Ross Boylan, Brandon K Bellows, Yiyi Zhang, Andrew E Moran, Dhruv S Kazi, Kirsten Bibbins-Domingo
Journal: Circulation (2022)

Background: Dietary intake of fruit and vegetables (FV) in the US falls well below recommended guidelines with only 12.2% of adults consuming at least 1.5-2 cup equivalents of fruit and 9.3% consuming at least 2-3 cup equivalents of vegetables each day. The Dietary Approaches to Stop Hypertension (DASH) trial demonstrated that consuming a “Mediterranean diet” with increased average daily FV intake resulted in reductions of systolic blood pressure of 0.8mmHg in those without hypertension and 7.2mmHg in those with hypertension. We used simulation modeling to estimate the impact of increasing FV intake in the population who currently are low FV consumers on subsequent incident cardiovascular disease (CVD) and death. Methods: We used the CVD Policy Model, a dynamic state-transition model of CVD risk factors, events, and outcomes to simulate the impact of increasing FV intake by one cup equivalent per day in US adults aged 35-94 years with no prior CVD who consume less than cup equivalent of FV per day; based on the National Health and Nutrition Examination Survey (NHANES) years 2015-2018. We used estimates of FV intake on blood pressure reductions based on DASH and ran 10 year simulations, focusing on the population with uncontrolled hypertension (baseline systolic BP ≥140mmHg). Results: Based on NHANES, 40.5M US adults age 35-94 years without a history of CVD consume less than 1 cup equivalent of FV per day. Increasing FV intake by cup equivalents per day in this population is estimated to prevent 98,000 incident CVD and 16,000 CVD deaths over 10 years, of which 82,000 (84%) and 13,000 (81%) respectively occur in 8.9M of this population with uncontrolled hypertension. Women would be expected to realize the greatest population improvements with increase in FV consumption. Conclusion: Increasing fruit and vegetable consumption among US adults could yield considerable population health benefits in prevention of cardiovascular disease and death, particularly for those with existing hypertension.
Changes in prevalence of violence and risk factors for violence and HIV among children and young people in Kenya: a comparison of the 2010 and 2019 Kenya Violence Against Children and Youth Surveys
Authors: Francis B Annor, Laura F Chiang, Patricia R Oluoch, Vivienne Mang'oli, Marygorret Mogaka, Mary Mwangi, Anne Ngunjiri, Francis Obare, Thomas Achia, Pragna Patel, Greta M Massetti, Linda L Dahlberg, Thomas R Simon, James A Mercy
Journal: The Lancet Global Health (2021)
Single low‐dose exposure to cow’s milk at diagnosis accelerates cow’s milk allergic infants’ progress on a milk ladder programme
Authors: Yvonne M. d’Art, Lisa Forristal, Aideen M. Byrne, John Fitzsimons, Ronald van Ree, Audrey DunnGalvin, Jonathan O'Brien Hourihane
Journal: Allergy (2022)

Abstract Background Cow's milk protein allergy (CMPA) is one of the most common food allergies in infancy. Most infants with CMPA tolerate baked milk from diagnosis and gradually acquire increased tolerance. Nevertheless, parents often display significant anxiety about this condition and a corresponding reluctance to progress with home introduction of dairy due to concerns about possible allergic reactions. Objective To evaluate the impact on gradual home introduction of foods containing cows’ milk after a supervised, single low‐dose exposure to whole milk at time of diagnosis. Methods Infants less than 12 months old referred with suspected IgE‐mediated cow's milk allergy were recruited to an open‐label randomized, controlled trial of intervention—a single dose of fresh cow's milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects—the ED 05 – vs routine care. Both groups implemented graded exposure to CM (using the 12 step MAP Milk Tolerance Induction Ladder), at home. Parents completed food allergy quality of life questionnaires and State and Trait Anxiety Inventories (STAI). Main outcome measures were milk ladder position at 6 months and 12 months post‐randomization. Results Sixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months, 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects ( p = .048). By 6 months, 11/37 (30%) intervention subjects had reached step 12 (i.e. drinking unheated cow's milk) compared to 2/20 (10%) of the controls ( p = .049). Twelve months post‐randomization, 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group ( p = .03). Maternal STAIs were significantly associated with their infants’ progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months. Conclusion This study demonstrates the safety and effectiveness of introduction of baked milk implemented immediately after diagnosis of cows’ milk allergy in a very young cohort. A supervised single dose of milk at the ED 05 significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants’ progress towards completion of the milk ladder, but pre‐existing high levels of maternal anxiety are associated with poorer progress.
The Role of 68Ga-DOTA-SSA PET/CT in the Management and Prediction of Peptide Receptor Radionuclide Therapy Response for Patients With Neuroendocrine Tumors
Authors: Osher Ngo Yung Lee, Kel Vin Tan, Vrijesh Tripathi, Hui Yuan, Wendy Wing-Lok Chan, Keith Wan Hang Chiu
Journal: Clinical Nuclear Medicine (2022)

Purpose The aim of this study was to identify and evaluate the role of 68 Ga-DOTA–somatostatin analog (SSA) PET/CT in guiding treatment for patients with neuroendocrine tumors (NETs) based on published literature, with specific focus on the ability of PET/CT to impact clinical management and predict peptide receptor radionuclide therapy (PRRT) response. Patients and Methods A systematic literature search of articles up to December 2021 was performed using PubMed and Scopus. Eligible studies included ≥10 patients with confirmed or suspected NETs who had undergone pretreatment staging 68 Ga-DOTA-SSA PET/CT. A meta-analysis using the random-effects model was conducted to determine the overall change in management after PET/CT, whereas PET/CT-derived parameters that correlated with PRRT outcome were summarized from studies that assessed its predictive capabilities. Results A total of 39 studies were included in this systemic review, of which 2266 patients from 24 studies were included for meta-analysis. We showed that PET/CT resulted in a change in clinical management in 36% (95% confidence interval, 31%–41%; range, 3%–66%) of patients. Fifteen studies consisting of 618 patients examined the prognostic ability of 68 Ga-DOTA-SSA PET/CT for PRRT. Of those, 8 studies identified a higher pretreatment SUV to favor PRRT, and 4 identified PET-based radiomic features for somatostatin receptor heterogeneity to be predictive of PRRT response. Conclusions Along with its diagnostic abilities, 68 Ga-DOTA-SSA PET/CT can impact treatment decision-making and may predict PRRT response in patients with NETs. More robust studies should be conducted to better elucidate the prognostic role of somatostatin receptor PET/CT in optimizing treatment for clinical outcome.
113P Proton-therapy and concurrent chemotherapy in stage III NSCLC: Effects on durvalumab eligibility and safety profile
Authors: F. Cortiula, D. De Ruysscher, S. Dursun, M. Steens, G. Bootsma, R. Canters, I. Rinaldi, V.T. Taasti, R. Houben, K. Reynders, S. Peeters, A. Angrisani, D. Hattu, L. Hendriks
Journal: Annals of Oncology (2022)
Chronic Pancreatitis
Authors: Santhi Swaroop Vege, Suresh T. Chari
Journal: New England Journal of Medicine (2022)

Chronic pancreatitis, often associated with alcohol use, smoking, or genetic risk factors, may be complicated by pseudocysts, biliary strictures, pancreatic insufficiency, bone loss, and pancreatic cancer. Aspects of management include structural and nonstructural interventions for pain and treatment with pancreatic-enzyme replacement.
Serial Assessment of High-Sensitivity Cardiac Troponin and the Effect of Dapagliflozin in Patients With Heart Failure With Reduced Ejection Fraction: An Analysis of the DAPA-HF Trial
Authors: David D. Berg, Kieran F. Docherty, Naveed Sattar, Petr Jarolim, Paul Welsh, Pardeep S. Jhund, Inder S. Anand, Vijay Chopra, Rudolf A. de Boer, Mikhail N. Kosiborod, Jose C. Nicolau, Eileen O’Meara, Morten Schou, Ann Hammarstedt, Anna-Maria Langkilde, Daniel Lindholm, Mikaela Sjöstrand, John J.V. McMurray, Marc S. Sabatine, David A. Morrow
Journal: Circulation (2021)

Circulating high-sensitivity cardiac troponin T (hsTnT) predominantly reflects myocardial injury, and higher levels are associated with a higher risk of worsening heart failure and death in patients with heart failure with reduced ejection fraction. Less is known about the prognostic significance of changes in hsTnT over time, the effects of dapagliflozin on clinical outcomes in relation to baseline hsTnT levels, and the effect of dapagliflozin on hsTnT levels.DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) was a randomized, double-blind, placebo-controlled trial of dapagliflozin (10 mg daily) in patients with New York Heart Association class II to IV symptoms and left ventricular ejection fraction ≤40% (median follow-up, 18.2 months). hsTnT (Roche Diagnostics) was measured at baseline in 3112 patients and at 1 year in 2506 patients. The primary end point was adjudicated worsening heart failure or cardiovascular death. Clinical end points were analyzed according to baseline hsTnT and change in hsTnT from baseline to 1 year. Comparative treatment effects on clinical end points with dapagliflozin versus placebo were assessed by baseline hsTnT. The effect of dapagliflozin on hsTnT was explored.Median baseline hsTnT concentration was 20.0 (25th-75th percentile, 13.7-30.2) ng/L. Over 1 year, 67.9% of patients had a ≥10% relative increase or decrease in hsTnT concentrations, and 43.5% had a ≥20% relative change. A stepwise gradient of higher risk for the primary end point was observed across increasing quartiles of baseline hsTnT concentration (adjusted hazard ratio Q4 versus Q1, 3.44 [95% CI, 2.46-4.82]). Relative and absolute increases in hsTnT over 1 year were associated with higher subsequent risk of the primary end point. The relative reduction in the primary end point with dapagliflozin was consistent across quartiles of baseline hsTnT (P-interaction=0.55), but patients in the top quartile tended to have the greatest absolute risk reduction (absolute risk difference, 7.5% [95% CI, 1.0%-14.0%]). Dapagliflozin tended to attenuate the increase in hsTnT over time compared with placebo (relative least squares mean reduction, -3% [-6% to 0%]; P=0.076).Higher baseline hsTnT and greater increase in hsTnT over 1 year are associated with worse clinical outcomes. Dapagliflozin consistently reduced the risk of the primary end point, irrespective of baseline hsTnT levels. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
Neuronal STAT3/HIF-1α/PTRF axis-mediated bioenergetic disturbance exacerbates cerebral ischemia-reperfusion injury via PLA2G4A
Authors: Weili Jin, Jixing Zhao, Eryan Yang, Yunfei Wang, Qixue Wang, Ye Wu, Fei Tong, Yanli Tan, Junhu Zhou, Chunsheng Kang
Journal: Theranostics (2022)

Ischemic stroke is an acute and severe neurological disease with high mortality and disability rates worldwide.Polymerase I and transcript release factor (PTRF) plays a pivotal role in regulating cellular senescence, glucose intolerance, lipid metabolism, and mitochondrial bioenergetics, but its mechanism, characteristics, and functions in neuronal cells following the cerebral ischemia-reperfusion (I/R) injury remain to be determined.Methods: Transcription factor motif analysis, chromatin immunoprecipitation (ChIP), luciferase and co-Immunoprecipitation (co-IP) assays were performed to investigate the mechanisms of PTRF in neuronal cells after I/R injury.Lentiviral-sgRNA against PTRF gene was introduced to HT22 cells, and adeno-associated virus (AAV) encoding a human synapsin (hSyn) promoter-driven construct was transduced a short hairpin RNA (shRNA) against PTRF mRNA in primary neuronal cells and the cortex of the cerebral I/R mice for investigating the role of PTRF in neuronal damage and PLA2G4A change induced by the cerebral I/R injury.Results: Here, we reported that neuronal PTRF was remarkably increased in the cerebral penumbra after I/R injury, and HIF-1α and STAT3 regulated the I/R-dependent expression of PTRF via binding to its promoter in neuronal cells.Moreover, overexpression of neuronal PTRF enhanced the activity and stability of PLA2G4A by decreasing its proteasome-mediated degradation pathway.Subsequently, PTRF promoted reprogramming of lipid metabolism and altered mitochondrial bioenergetics, which could lead to oxidative damage, involving autophagy, lipid peroxidation, and ferroptosis via PLA2G4A in neuronal cells.Furthermore, inhibition of neuronal PTRF/PLA2G4A-axis markedly reduced the neurological deficits, cerebral infarct volumes, and mortality rates in the mice following cerebral I/R injury.Conclusion: Our results thus identify that the STAT3/HIF-1α/PTRF-axis in neurons, aggravating cerebral I/R injury by regulating the activity and stability of PLA2G4A, might be a novel therapeutic target for ischemic stroke.
Abstract 11037: Procedural Success, Valve Hemodynamics and Outcomes in Patients with Moderate Aortic Stenosis Undergoing Supra-Annular Transcatheter Aortic Valve Replacement
Authors: Ravi Sharma, Roger J Laham, Paul Sorajja, Binita Shah, Santiago Garcia, Renuka Jain, Eric Fender, Femi Philip, Ruth Eisenberg, Stanley Chetcuti
Journal: Circulation (2021)

Introduction: Limited evidence supports the hypothesis that early treatment of symptomatic moderate aortic stenosis (AS) may be beneficial. We seek to study procedural success, valve hemodynamics and clinical outcomes in moderate AS patients who underwent transcatheter aortic valve replacement (TAVR) using a supra-annular self-expanding bioprosthesis. Methods: All patients in the STS/ACC/TVT Registry™ with Evolut R, PRO and PRO+ attempted procedures for indication of primary symptomatic (NYHA class II-IV) moderate AS were included. Moderate AS was defined as mean gradient ≥20 and &lt;40 mm Hg, valve area &gt;1.0 and &lt;1.5 cm 2 , and Vmax &gt;3 and &lt;4 m/s. 2.9% of patients had concurrent severe aortic regurgitation at baseline. Valve-in-valve procedures were excluded. Site reported 30-day event rates are reported using Kaplan-Meier analysis. As a quality-of-life metric, KCCQ scores at 30 days and 1 year are compared to baseline scores using paired t-tests. Results: A total of 811 patients (62.1% men, 77.7 ± 8.7 years of age, STS-PROM score 5.3 ± 3.6, baseline LVEF 56.7 ± 13.3 %) were analyzed. The majority of patients underwent elective procedure (n=762, 94.0%) under conscious sedation (n=439, 54.3%) via iliofemoral approach (n=775, 95.6%). Successful device implantation, defined as correct valve positioning, was achieved in 99.3% of patients with low rates of intraprocedural complications (0.4%). Clinical events at 30 days were: all-cause mortality 1.4%, neurological events 2.5%, major bleeding 4.7% and conduction disturbance requiring pacer/ICD 16.1%. Valve hemodynamics improved post procedure compared to baseline (mean gradient 29.8 ± 4.9 to 8.4 ± 4.9 mm Hg, Vmax 3.5 ± 0.2 to 1.9 ± 0.5 m/s), with mean gradient sustained at 1 year (8.6 ± 4.4 mm Hg). Moderate/severe paravalvular regurgitation was present at similar levels at post procedure and 1 year (1.6% and 3.0%). A significant improvement in quality of life was noted from baseline KCCQ score to 30 days (Δ27.5 ± 25.5, 95% CI 25.4 - 29.5, p&lt;0.001) and 1 year (Δ29.1 ± 26.1, 95% CI 26.2 - 32.1, p&lt;0.001). Conclusions: Patients undergoing TAVR with a self-expanding bioprosthesis for symptomatic moderate AS have high procedural success with sustained improvements in valve hemodynamics and quality of life at 30 days and 1 year.
Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer
Authors: Wan Xing Hong, Idit Sagiv-Barfi, Debra K. Czerwinski, Adrienne Sallets, Ronald Levy
Journal: Cancer Research (2022)

The combination of the synthetic TLR9 ligand CpG and agnostic OX40 antibody can trigger systemic antitumor immune responses upon co-injection into the tumor microenvironment, eradicating simultaneous untreated sites of metastatic disease. Here we explore the application of this in situ immunotherapy to the neoadjuvant setting. Current neoadjuvant checkpoint blockade therapy is delivered systemically, resulting in off-target adverse effects. In contrast, intratumoral immunotherapy minimizes the potential for toxicities and allows for greater development of combination therapies. In two metastatic solid tumor models, neoadjuvant intratumoral immunotherapy generated a local T-cell antitumor response that then acted systemically to attack cancer throughout the body. In addition, the importance of timing between neoadjuvant immunotherapy and surgical resection was established, as well as the increased therapeutic power of adding systemic anti-PD1 antibody. The combination of local and systemic immunotherapy generated an additional survival benefit due to synergistic inhibitory effect on tumor-associated macrophages. These results provide a strong rationale for translating this neoadjuvant intratumoral immunotherapy to the clinical setting, especially in conjunction with established checkpoint inhibitors.
Genetic Analysis of Lung Cancer and the Germline Impact on Somatic Mutation Burden
Authors: Aurélie A G Gabriel, Joshua R Atkins, Ricardo C C Penha, Karl Smith-Byrne, Valerie Gaborieau, Catherine Voegele, Behnoush Abedi-Ardekani, Maja Milojevic, Robert Olaso, Vincent Meyer, Anne Boland, Jean François Deleuze, David Zaridze, Anush Mukeriya, Beata Swiatkowska, Vladimir Janout, Miriam Schejbalová, Dana Mates, Jelena Stojšić, Miodrag Ognjanovic, John S Witte, Sara R Rashkin, Linda Kachuri, Rayjean J Hung, Siddhartha Kar, Paul Brennan, Anne-Sophie Sertier, Anthony Ferrari, Alain Viari, Mattias Johansson, Christopher I Amos, Matthieu Foll, James D McKay
Journal: JNCI Journal of the National Cancer Institute (2022)

Germline genetic variation contributes to lung cancer (LC) susceptibility. Previous genome-wide association studies (GWAS) have implicated susceptibility loci involved in smoking behaviors and DNA repair genes, but further work is required to identify susceptibility variants.