tbuckley/cabot-search huggingface dataset:
Abstract P106: Estimating The Difference In CVD Prevalence Among Patients With OUD Identified By NLP &amp; ICD-10-CM Codes Using EHR Data
Authors: Jade Singleton, Peter Akpunonu, Erin Abner, Anna Kucharska-newton
Journal: Circulation (2022)

Background: Diagnostic codes may underestimate the prevalence of opioid use disorder, especially among complex patients. We estimated the prevalence of cardiovascular disease (CVD) among patients with OUD identified from electronic health records (EHR) from ICD-10-CM diagnostic codes and by natural language processing (NLP) of clinical notes. Methods: We conducted a cross-sectional study using anonymized EHR from one academic medical center, representing inpatient and emergency department visits for 2019. Patients with OUD were identified by ICD-10-CM (ICD) codes and by a rule-based NLP algorithm applied to unstructured EHR clinical notes. CVD was identified using ICD codes for acute myocardial infarction, cardiac arrhythmia, stroke, heart failure, ischemic heart disease (IHD), and infective endocarditis (IE). We estimated crude prevalence of CVD diagnoses (overall and by type) for patients with OUD identified by ICD codes and NLP. Results: Among 22,701 patients, 1,878 were identified as having OUD, of which 1,483 (79%) were identifiable by ICD codes and 395 were only identifiable from clinical notes using NLP (Table 1). Patients identified only by NLP tended to be older, more likely African American and more likely Hispanic relative to patients identified by ICD. The prevalence of any CVD among all patients with OUD was 44.7% (841/1878). Prevalence of IE was very low in both groups. For the other CVD types, between 17-29% of diagnoses were among OUD patients found only by NLP. Conclusion: NLP can recover OUD cases from unstructured notes that cannot be identified by ICD codes alone. If relying on ICD codes alone to identify OUD from EHR, researchers may underestimate prevalence of both OUD and CVD among patients with OUD (e.g. heart failure, IHD), or overestimate the prevalence of conditions, such as IE. * CVD was ascertained via ICD codes. Results are n, row %, for ‘ICD-10-CM’ and ‘NLP only’ columns. For the Total column, results are n, column %.
Posterior left pericardiotomy for the prevention of atrial fibrillation after cardiac surgery: an adaptive, single-centre, single-blind, randomised, controlled trial
Authors: Mario Gaudino, Tommaso Sanna, Karla V Ballman, N Bryce Robinson, Irbaz Hameed, Katia Audisio, Mohamed Rahouma, Antonino Di Franco, Giovanni J Soletti, Christopher Lau, Lisa Q Rong, Massimo Massetti, Marc Gillinov, Niv Ad, Pierre Voisine, J Michael DiMaio, Joanna Chikwe, Stephen E Fremes, Filippo Crea, John D Puskas, Leonard Girardi
Journal: The Lancet (2021)
Phase I/IIa Trial of BMS-986148, an Anti-mesothelin Antibody–drug Conjugate, Alone or in Combination with Nivolumab in Patients with Advanced Solid Tumors
Authors: Sylvie Rottey, Jeffrey Clarke, Kyaw Aung, Jean-Pascal Machiels, Ben Markman, Kimberley M. Heinhuis, Michael Millward, Martijn Lolkema, Sandip Pravin Patel, Paul de Souza, Matteo Duca, Giuseppe Curigliano, Armando Santoro, Takafumi Koyama, Michelle Brown, Heather Vezina, Chunsheng He, Quincy Siu-Chung Chu
Journal: Clinical Cancer Research (2021)

Abstract Purpose: To assess the safety and tolerability of BMS-986148, a mesothelin-directed antibody–drug conjugate (ADC) ± nivolumab, in patients with selected tumors. Patients and Methods: In an international phase I/IIa study [NCT02341625 (CA008-002)], patients received BMS-986148 monotherapy (0.1–1.6 mg/kg intravenously (i.v.) every 3 weeks or 0.4 or 0.6 mg/kg i.v. once weekly; n = 96) or BMS-986148 0.8 mg/kg + nivolumab 360 mg i.v. every 3 weeks (n = 30). The primary endpoint was safety and tolerability. Results: In CA008-002, the most common (≥ 10%) treatment-related adverse events (TRAEs) included increased aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Grade 3/4 TRAEs occurred in 42 patients (49%) receiving BMS-986148 every 3 weeks monotherapy, three (25%) receiving BMS-986148 once-weekly monotherapy, and 10 (33%) receiving BMS-986148 + nivolumab every 3 weeks. Overall, 17 of 126 patients (13%) discontinued because of a TRAE. The MTD of BMS-986148 was 1.2 mg/kg i.v. every 3 weeks. The safety profile of BMS-986148 + nivolumab was similar to that of BMS-986148 monotherapy (0.8 mg/kg). Active ADC exposures increased in a dose-proportional manner with both dosing regimens (every 3 weeks and once weekly). Preliminary clinical activity was observed with BMS-986148 ± nivolumab. No association between mesothelin expression and response was detected. Conclusions: BMS-986148 ± nivolumab demonstrated a clinically manageable safety profile and preliminary evidence of clinical activity, supporting additional studies combining directed cytotoxic therapies with checkpoint inhibitors as potential multimodal therapeutic strategies in patients with advanced solid tumors.
166P Integrated analysis reveals TP53 mutation as a biomarker of anti-PD-1/PD-L1 treatment for epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients
Authors: S. Wang, T. Xie, Y. Wang, X. Hao, P. Yuan, Q. Cao, H. Wang, L. Lin, J. Ying, J. Li, P. Xing
Journal: Annals of Oncology (2022)
Abstract 10712: Observational Findings of PULS Cardiac Test Findings for Inflammatory Markers in Patients Receiving mRNA Vaccines
Authors: Steven R Gundry
Journal: Circulation (2021)

This clinic has been using the PULS Cardiac Test (Predictive Health Diagnostics Co., Irvine, CA) a clinically utilized measurement of multiple protein biomarkers, which generates a score predicting the 5 yr risk (percentage chance) of a new Acute Coronary Syndrome (ACS) called the PULS Score. The score is based on changes from the norm of multiple protein inflammatory biomarkers including IL-16, a proinflammatory cytokine, soluble Fas, an inducer of apoptosis, and Hepatocyte Growth Factor (HGF) which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue, among other markers. Elevation above the norm increases the PULS score, while decreases below the norm lowers the PULS score. The PULS score has been measured every 3-6 months in our patient population for 8 years. Recently, with the advent of the mRNA COVID 19 vaccines (vac) by Moderna and Pfizer, we tracked the changes of the PULS score and three of the inflammatory markers it measures in all of our patients consecutively receiving these vaccines. This report summarizes those results. A total of 566 pts, aged 28 to 97, M:F ratio 1:1 seen in a preventive cardiology practice had a previously scheduled PULS test drawn from 2 to 10 weeks following the 2 nd mRNA COVID shot and was compared to the pt’s PULS test drawn 3 to 5 months previously pre-shot. Each vac pt’s PULS score and inflammatory marker changes were compared to their pre-vac PULS score, thus serving as their own control. There was no comparison made with unvaccinated patients or pts treated with other vaccines. Baseline IL-16 increased from 35+/-20 above the norm to 82 +/- 75 above the norm post-vac; sFas increased from 22+/- 15 above the norm to 46+/-24 above the norm post vac; HGF increased from 42+/-12 above the norm to 86+/-31 above the norm post vac. These changes resulted in an increase of the pre vac PULS score of predicted 11% 5 yr ACS risk to a post vac PULS score of a predicted 25% 5 yr ACS risk, based on data which has not been validated in this population. No statistical comparison was done in this observational study. In conclusion, the mRNA vacs numerically increase (but not statistically tested) the markers IL-16, Fas, and HGF, all markers previously described by others for denoting inflammation on the endothelium and T cell infiltration of cardiac muscle, in a consecutive series of a single clinic patient population receiving mRNA vaccines without a control group.
Unusual Radiotracer Deposition to the Forearm After Intrahepatic Injection of 99mTc-Macroaggregated Albumin Using a Transradial Approach
Authors: Jon Mugweru, Shana Elman, William J. Rieter, Christopher Gutjahr, Saeed Elojeimy
Journal: Clinical Nuclear Medicine (2022)

Abstract Arterial mapping and 99m Tc-macroaggregated albumin ( 99m Tc-MAA) hepatic perfusion imaging are routinely performed before 90 Y radioembolization of hepatic tumors. These procedures serve multiple purposes, including an anatomical survey of hepatic arterial anatomy, interrogating expected microsphere distribution to avoid nontargeted embolization during therapy, and evaluating for possible hepatopulmonary shunting. We present a case where 99m Tc-MAA planar images revealed unexpected soft tissue uptake within the left forearm, an unexpected complication that may result from residual 99m Tc-MAA in the catheter being expelled as the catheter is removed, which is particularly important to avoid during the 90 Y radioembolization procedure given the risk for associated radionecrosis.
Quantification of Neoantigen-Mediated Immunoediting in Cancer Evolution
Authors: Tao Wu, Guangshuai Wang, Xuan Wang, Shixiang Wang, Xiangyu Zhao, Chenxu Wu, Wei Ning, Ziyu Tao, Fuxiang Chen, Xue-Song Liu
Journal: Cancer Research (2022)

Abstract Immunoediting includes three temporally distinct stages, termed elimination, equilibrium, and escape, and has been proposed to explain the interactions between cancer cells and the immune system during the evolution of cancer. However, the status of immunoediting in cancer remains unclear, and the existence of neoantigen depletion in untreated cancer has been debated. Here we developed a distribution pattern-based method for quantifying neoantigen-mediated negative selection in cancer evolution. The method can provide a robust and reliable quantification for immunoediting signal in individual patients with cancer. Moreover, this method demonstrated the prevalence of immunoediting in the immunotherapy-naive cancer genome. The elimination and escape stages of immunoediting can be quantified separately, where tumor types with strong immunoediting-elimination exhibit a weak immunoediting-escape signal, and vice versa. The quantified immunoediting-elimination signal was predictive of clinical response to cancer immunotherapy. Collectively, immunoediting quantification provides an evolutionary perspective for evaluating the antigenicity of neoantigens and reveals a potential biomarker for precision immunotherapy in cancer. Significance: Quantification of neoantigen-mediated negative selection in cancer progression reveals distinct features of cancer immunoediting and can serve as a potential biomarker to predict immunotherapy response.
168P Characterization of the lung tumor microenvironment upon anti-PD-L1 therapy reveals an ambiguous role for TNF-α
Authors: K. De Ridder, H. Locy, E. Piccioni, M. Ibarra Zuazo, R.M. Awad, S. Verhulst, M. van Bulck, Y. De Vlaeminck, Q. Lecocq, E. Reijmen, W. De Mey, L. De Beck, T. Ertveldt, I. Pintelon, J-P. Timmermans, D. Escors, M. Keyaerts, K. Breckpot, C. Goyvaerts
Journal: Annals of Oncology (2022)
Abstract MP59: Association Between Time-varying Sleep Quality Status And Hypertriglyceridemia Onset In Middle-aged Population
Authors: Ga Bin Lee, Sun Jae Jung, Eun Lee, Song Vogue Ahn, Kyoung Min Kim, Hyeon Chang Kim
Journal: Circulation (2022)

Introduction: Deteriorated sleep quality adversely affects insulin sensitivity and inflammation markers, and these factors are commonly associated with triglyceride levels. However, the long-term effects of sleep quality on fasting triglyceride levels have not been investigated in previous studies. Hypothesis: We assessed the hypothesis that whether time-varying sleep quality affects the risk of hypertriglyceridemia among healthy middle-aged Koreans. Methods: Participants in the Korean Genome and Epidemiology Study were biennially followed up from the baseline. Sleep quality was assessed five times measured over 14 years by the Pittsburgh Sleep Quality Index (PSQI). We utilized data on 1,773 participants (mean age: 49.8) with at least three measures of sleep quality data and without dyslipidemia at baseline. Poor sleep was determined as PSQI &gt;7. Blood samples were collected from every survey and the first visit of triglyceride≥200 mg/dL was defined as hypertriglyceridemia. Cox proportional hazard models with time-varying sleep quality were employed to estimate the effects of time-varying sleep quality on the risk of hypertriglyceridemia. Adjusted covariates included age, socioeconomic factors, body mass index, baseline blood lipids, insulin sensitivity, menopausal status, psychological stress, comorbidities, frequency of night-snack, smoking, drinking, and physical activity. All analyses were conducted separately in men and women. Results: During a median follow-up of 11.8 years, 233 men (28.2%) and 192 women (20.1%) developed hypertriglyceridemia. Sleep quality as a time-varying element was significantly associated with the risk of developing hypertriglyceridemia in women after full adjustments; poor sleep increased 53% of hazards for developing hypertriglyceridemia in women (hazard ratio 1.53; 95% confidence interval 1.07-2.17), but not in men (hazard ratio 1.03; 95% confidence interval 0.68-1.55). A sensitivity analysis, which was adjusted for a time-varying status of alcohol drinking and physical activity, showed similar findings. Another sensitivity results with the complete case of sleep quality data were similar to the main results. Conclusions: In conclusion, maintaining good sleep quality may have cardiovascular prevention effects, through preventing hypertriglyceridemia, in middle-aged women.
Correction: Genetic Dissociation of Glycolysis and the TCA Cycle Affects Neither Normal nor Neoplastic Proliferation
Authors: Laura E. Jackson, Sucheta Kulkarni, Huabo Wang, Jie Lu, James M. Dolezal, Sivakama S. Bharathi, Sarangarajan Ranganathan, Mulchand S. Patel, Rahul Deshpande, Frances Alencastro, Stacy G. Wendell, Eric S. Goetzman, Andrew W. Duncan, Edward V. Prochownik
Journal: Cancer Research (2022)

In the original version of this article (1), there was an error in Fig. 3H. Specifically, the panel showing pPDH staining in crowded fetal (lower rightmost) was an inadvertent duplication of the panel showing PDH staining in crowded fetal directly above it. The correct images have been provided, and the errors have been corrected in the latest HTML and PDF versions of the article. The authors regret this error.
Waning Immunity after the BNT162b2 Vaccine in Israel
Authors: Yair Goldberg, Micha Mandel, Yinon M. Bar-On, Omri Bodenheimer, Laurence Freedman, Eric J. Haas, Ron Milo, Sharon Alroy-Preis, Nachman Ash, Amit Huppert
Journal: New England Journal of Medicine (2021)

In December 2020, Israel began a mass vaccination campaign against coronavirus disease 2019 (Covid-19) by administering the BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a resurgent Covid-19 outbreak began in mid-June 2021. Possible reasons for the resurgence were reduced vaccine effectiveness against the delta (B.1.617.2) variant and waning immunity. The extent of waning immunity of the vaccine against the delta variant in Israel is unclear.We used data on confirmed infection and severe disease collected from an Israeli national database for the period of July 11 to 31, 2021, for all Israeli residents who had been fully vaccinated before June 2021. We used a Poisson regression model to compare rates of confirmed SARS-CoV-2 infection and severe Covid-19 among persons vaccinated during different time periods, with stratification according to age group and with adjustment for possible confounding factors.Among persons 60 years of age or older, the rate of infection in the July 11-31 period was higher among persons who became fully vaccinated in January 2021 (when they were first eligible) than among those fully vaccinated 2 months later, in March (rate ratio, 1.6; 95% confidence interval [CI], 1.3 to 2.0). Among persons 40 to 59 years of age, the rate ratio for infection among those fully vaccinated in February (when they were first eligible), as compared with 2 months later, in April, was 1.7 (95% CI, 1.4 to 2.1). Among persons 16 to 39 years of age, the rate ratio for infection among those fully vaccinated in March (when they were first eligible), as compared with 2 months later, in May, was 1.6 (95% CI, 1.3 to 2.0). The rate ratio for severe disease among persons fully vaccinated in the month when they were first eligible, as compared with those fully vaccinated in March, was 1.8 (95% CI, 1.1 to 2.9) among persons 60 years of age or older and 2.2 (95% CI, 0.6 to 7.7) among those 40 to 59 years of age; owing to small numbers, the rate ratio could not be calculated among persons 16 to 39 years of age.These findings indicate that immunity against the delta variant of SARS-CoV-2 waned in all age groups a few months after receipt of the second dose of vaccine.
ADOPTING PERMANENT HIS BUNDLE PACING: LEARNING CURVES AND MEDIUM-TERM OUTCOMES
Authors: Pipin Kojodjojo, Jhobeleen De Leon, Elaine Boey, Rodney Soh, Eugene Tan, Colin Yeo, Vern Hsen Tan, Swee Chong Seow
Journal: Journal of the American College of Cardiology (2022)
HDACs and the epigenetic plasticity of cancer cells: Target the complexity
Authors: Claudio Brancolini, Teresa Gagliano, Martina Minisini
Journal: Pharmacology & Therapeutics (2022)

Cancer cells must adapt to the hostile conditions of the microenvironment in terms of nutrition, space, and immune system attack. Mutations of DNA are the drivers of the tumorigenic process, but mutations must be able to hijack cellular functions to sustain the spread of mutant genomes. Transcriptional control is a key function in this context and is controlled by the rearrangement of the epigenome. Unlike genomic mutations, the epigenome of cancer cells can in principle be reversed. The discovery of the first epigenetic drugs triggered a contaminating enthusiasm. Unfortunately, the complexity of the epigenetic machinery has frustrated this enthusiasm. To develop efficient patient-oriented epigenetic therapies, we need to better understand the nature of this complexity. In this review, we will discuss recent advances in understanding the contribution of HDACs to the maintenance of the transformed state and the rational for their selective targeting.
Recurrence of Anti-Semaphorin 3B–Mediated Membranous Nephropathy after Kidney Transplantation
Authors: Marc Fila, Hanna Debiec, Hélène Perrochia, Nabila Djouadi, Marie-Christine Verpont, David Buob, Pierre Ronco
Journal: Journal of the American Society of Nephrology (2022)

Membranous nephropathy (MN) is rare in pediatric patients, although its diagnosis may be underestimated in children who are responsive to corticosteroid therapy prescribed for a suspicion of minimal change disease. It is most often associated with an autoimmune disease, predominantly lupus. We previously reported the occurrence of early-onset MN associated with semaphorin 3B in nine children and two adults.Biopsies were performed on native kidney and at 1 and 5 months after transplantation. Semaphorin 3B antigen was detected in immune deposits by immunohistochemistry and confocal microscopy on paraffin-embedded biopsies. Anti-semaphorin antibodies were detected by Western blot and analyzed sequentially.We report the first case of early recurrence after transplantation in a 7-year-old boy who presented with severe nephrotic syndrome and advanced kidney failure. There was no evidence of hereditary or associated autoimmune disease. Abundant, almost coalescent deposits were seen by electron microscopy and bright granular, subepithelial staining was observed for semaphorin 3B antigen. Western blot analysis of serum revealed anti-semaphorin 3B antibodies. Recurrence of MN occurred 25 days after transplantation and manifested as nephrotic range proteinuria despite conventional immunosuppressive therapy. Kidney biopsies confirmed histologic MN recurrence with colocalization of semaphorin 3B antigen and IgG. The patient was treated with rituximab. Anti-semaphorin 3B antibodies, which were detected at transplantation, were not detected 40 days after rituximab.This case provides evidence that anti-semaphorin 3B antibodies are pathogenic and should be monitored in patients with MN.
Rare and Common Variants in <i>KIF15</i> Contribute to Genetic Risk of Idiopathic Pulmonary Fibrosis
Authors: David Zhang, Gundula Povysil, Philippe H. Kobeissy, Qi Li, Binhan Wang, Mason Amelotte, Hager Jaouadi, Chad A. Newton, Toby M. Maher, Philip L. Molyneaux, Imre Noth, Fernando J. Martinez, Ganesh Raghu, Jamie L. Todd, Scott M. Palmer, Carolina Haefliger, Adam Platt, Slavé Petrovski, Joseph A. Garcia, David B. Goldstein, Christine Kim Garcia
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Genetic studies of idiopathic pulmonary fibrosis (IPF) have improved our understanding of this disease, but not all causal loci have been identified. Objectives: To identify genes enriched with rare deleterious variants in IPF and familial pulmonary fibrosis. Methods: We performed gene burden analysis of whole-exome data, tested single variants for disease association, conducted KIF15 (kinesin family member 15) functional studies, and examined human lung single-cell RNA sequencing data. Measurements and Main Results: Gene burden analysis of 1,725 cases and 23,509 control subjects identified heterozygous rare deleterious variants in KIF15, a kinesin involved in spindle separation during mitosis, and three telomere-related genes (TERT [telomerase reverse transcriptase], RTEL1 [regulator of telomere elongation helicase 1], and PARN [poly(A)-specific ribonuclease]). KIF15 was implicated in autosomal-dominant models of rare deleterious variants (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.7-8.8; P = 2.55 × 10-7) and rare protein-truncating variants (OR, 7.6; 95% CI, 3.3-17.1; P = 8.12 × 10-7). Meta-analyses of the discovery and replication cohorts, including 2,966 cases and 29,817 control subjects, confirm the involvement of KIF15 plus the three telomere-related genes. A common variant within a KIF15 intron (rs74341405; OR, 1.6; 95% CI, 1.4-1.9; P = 5.63 × 10-10) is associated with IPF risk, confirming a prior report. Lymphoblastoid cells from individuals heterozygous for the common variant have decreased KIF15 and reduced rates of cell growth. Cell proliferation is dependent on KIF15 in the presence of an inhibitor of Eg5/KIF11, which has partially redundant function. KIF15 is expressed specifically in replicating human lung cells and shows diminished expression in replicating epithelial cells of patients with IPF. Conclusions: Both rare deleterious variants and common variants in KIF15 link a nontelomerase pathway of cell proliferation with IPF susceptibility.
68Ga-FAPI and 18F-FDG PET/CT Findings in a Patient With Pancreatic Tuberculosis Mimicking Malignant Tumor
Authors: Rui Sun, Zhanwen Huang, Jing Wei, Chengrun Zeng, XiaoLiang Chen
Journal: Clinical Nuclear Medicine (2022)

Abstract We report the case of a 24-year-old man who presented with abdominal pain and jaundice. 18 F-FDG and 68 Ga-FAPI PET/CT showed increased radioactivity in the region of the pancreatic head, which suggested malignant tumor. However, postoperative pathological finding demonstrated the presence of tuberculosis. This case documents that the pancreatic tuberculosis may cause FAPI uptake, and nuclear medicine physician evaluating 68 Ga-FAPI imaging should be aware of this potential pitfall.