tbuckley/cabot-search huggingface dataset:
Progress Toward Poliomyelitis Eradication — Pakistan, January 2019−September 2020
Authors: Christopher H. Hsu, Muhammad Shafiq-ur Rehman, Kelley Bullard, Jaume Jorba, Milhia Kader, Hamish Young, Muhammad Safdar, Hamid S. Jafari, Derek Ehrhardt
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Pakistan and Afghanistan are the only countries where wild poliovirus type 1 (WPV1) is endemic (1,2). In 2019, Pakistan reported 147 WPV1 cases, approximately 12 times the number reported in 2018. As of September 15, 72 cases had been reported in 2020. Since 2019, WPV1 transmission has also spread from Pakistan's core poliovirus reservoirs (Karachi, Peshawar, and Quetta block) to southern districts of Khyber Pakhtunkhwa (KP), Punjab, and Sindh provinces. Further, an outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2), first detected in July 2019, has caused 22 paralytic cases in 2019 and 59 as of September 15, 2020, throughout the country. The coronavirus disease 2019 (COVID-19) pandemic has substantially reduced delivery of polio vaccines through essential immunization (formerly routine immunization) and prevented implementation of polio supplementary immunization activities (SIAs)* during March-July 2020. This report describes Pakistan's progress in polio eradication during January 2019-September 2020 and updates previous reports (1,3,4). The Pakistan polio program has reinitiated SIAs and will need large, intensive, high-quality campaigns with strategic use of available oral poliovirus vaccines (OPVs)† to control the surge and widespread transmission of WPV1 and cVDPV2.
Abstract 13887: Cardiac Troponin I and Bnp for Predicting Zero Agatston Score in Patients With Diabetes Mellitus
Authors: Theo Pezel, Jean Guillaume DILLINGER, Guillaume Bonnet, Tiphaine Vidal Trecan, Anouk Asselin, Georgios Sideris, Damien Logeart, Stéphane Manzo-Silberman, Jean François Gautier, Jean Pierre Riveline, Patrick Henry
Journal: Circulation (2020)

Introduction: Coronary artery calcifications (CAC) Agatston score has shown an excellent prognostic value and particularly in diabetic patients, with a very low rate of cardiovascular (CV) events in patients with zero CAC score. Recent studies have suggested that high-sensitive cardiac troponin I (hs-cTnI) and brain natriuretic peptide (BNP) may be useful to detect subclinical atherosclerosis. Hypothesis: To assess the predictive value of hs-cTnI and BNP to predict zero CAC score in diabetic patients. Methods: Between 2015 and 2019, CAC score was performed in consecutive patients with diabetes mellitus. Patients with symptoms, coronary artery disease or atrial fibrillation were excluded. Within 24h from CT examination, blood samples were taken to measure hs-cTnI and BNP. The relationship between hs-cTnI/BNP concentrations and zero CAC score was evaluated using univariate and multivariate binomial models, and nested models associated with Chi-squared test of independence. Results: Among 844 diabetic patients (61±7 years, 57% men, duration of diabetes 18 years), 35% had zero CAC score, 30% a score from 1-100, 19% from 101-400, and 16% &gt;400. Hs-cTnI/BNP were associated with zero CAC score (OR 2.63, 95%CI[1.51-5.01]; p&lt;0.001; OR 1.09, 95%CI[1.01-1.22]; p=0.03 respectively). In multivariate analysis, hs-cTnI/BNP were associated with zero CAC score (OR 2.38, 95%CI[1.51-4.76]; p=0.009; OR 1.18, 95%CI[1.07-1.32]; p=0.001 respectively). Among 77 variables, the multivariate model including age, gender, smoking, dyslipidaemia, duration of the diabetes, hypertension, diabetic neuropathy, hs-cTnI and BNP significantly discriminated the zero CAC score (AUC=0.81; p&lt;0.001). In nested models, both hs-cTnI and BNP brought information to this multivariate model to predict zero CAC score (p&lt;0.001). Conclusions: Biomarkers hs-cTnI and BNP are associated with zero CAC score in diabetic patients.
A review of machine learning methods for retinal blood vessel segmentation and artery/vein classification
Authors: Muthu Rama Krishnan Mookiah, Stephen Hogg, Tom J MacGillivray, Vijayaraghavan Prathiba, Rajendra Pradeepa, Viswanathan Mohan, Ranjit Mohan Anjana, Alexander S. Doney, Colin N.A. Palmer, Emanuele Trucco
Journal: Medical Image Analysis (2020)
HIGHLY EFFICIENT SINGLE-DOMAIN ANTIBODY NEUTRALIZATION OF INTERLEUKIN-6, THE FACTOR AT THE EPICENTER OF CYTOKINE STORM IN ACUTELY ILL COVID-19 PATIENTS
Authors: S. Ko, S. Hu, J. M. Tremblay, J. Erasmus, C. B. Shoemaker, J. C. Lopez-Talavera, V. Kansra, S. S. Monga
Journal: Hepatology (2020)

Background: COVID-19 is a worldwide medical emergency with a high mortality rate Cytokine storm (CS) has been attributed as the major cause of morbidity, multi-organ failure & mortality in COVID-19 patients In CS, the uncontrolled increase in pro-inflammatory cytokines especially IL6 results in an influx of immune cells leading to progressive tissue destruction Use of IL6 receptor (IL6R) inhibitors have shown only modest benefit in acutely ill COVID-19 cases due to need for high doses and associated side effects  More efficacious and safer agents to targets IL6 are thus urgently needed We report generation of a potent camelid single domain antibody (sdAb) that robustly neutralizes human IL6 (hIL6) Methods: Two alpacas were immunized with purified hIL6 & a sdAb display phage library was prepared The library was enriched by panning for sdAbs recognizing hIL6 One group of closely related sdAbs was identified, expressed as soluble proteins, that displayed sub-nM affinity for hIL6  These sdAbs were found to neutralize hIL6 with low pM potencies in cell-based assays The most potent sdAb was expressed in CHO cells as a homodimer separated by a short amino acid spacer The homodimer was also encoded in an alphavirus-based replicon RNA (repRNA) & formulated with a Lipid InOrganic Nanoparticle (LION) The homodimer protein & repRNA were tested in vitro & in vivo Results: HEK293 cells transfected with Stat3-luciferase were treated for 6h with 50ng of hIL6 alone or hIL6 co-incubated 1h with 100ng of sdAb A complete abrogation of reporter activity was observed in the sdAb group To mimic CS, adult mice were challenged intraperitoneally (IP) for 30 min with 1mg of hIL6 alone or with sdAb, ranging from 0 25-4mg hIL6-induced Y705-STAT3 induction in liver was completely abolished by sdAb dimer at concentration ≥0 5mg, an effect not seen even with 500mg of IL6R Ab  Mice were injected 5 days with an intramuscular injection of PBS or 40mg LION-formulated hIL6 sdAb dimer repRNA and then given 100ng of hIL6 IP for 30m LION-injected group showed complete absence of hepatic Y705-STAT3 in response to hIL6 Conclusion: The novel humanized IL6 sdAB efficiently inhibited hIL6-induced hepatic STAT3 activation and may have potential as a therapeutic for acutely ill COVID-19 patients exhibiting CS & other IL6-driven pathologies Additionally, using a similar pipeline, we are developing inhibitors of ACE2 and IL-1b, which can be combined for efficacious COVID-19 treatment
Open resource of clinical data from patients with pneumonia for the prediction of COVID-19 outcomes via deep learning
Authors: Wanshan Ning, Shijun Lei, Jingjing Yang, Yukun Cao, Peiran Jiang, Qianqian Yang, Jiao Zhang, Xiaobei Wang, Fenghua Chen, Zhi Geng, Liang Xiong, Hongmei Zhou, Yaping Guo, Yulan Zeng, Heshui Shi, Lin Wang, Yu Xue, Zheng Wang
Journal: Nature Biomedical Engineering (2020)

Abstract Data from patients with coronavirus disease 2019 (COVID-19) are essential for guiding clinical decision making, for furthering the understanding of this viral disease, and for diagnostic modelling. Here, we describe an open resource containing data from 1,521 patients with pneumonia (including COVID-19 pneumonia) consisting of chest computed tomography (CT) images, 130 clinical features (from a range of biochemical and cellular analyses of blood and urine samples) and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical status. We show the utility of the database for prediction of COVID-19 morbidity and mortality outcomes using a deep learning algorithm trained with data from 1,170 patients and 19,685 manually labelled CT slices. In an independent validation cohort of 351 patients, the algorithm discriminated between negative, mild and severe cases with areas under the receiver operating characteristic curve of 0.944, 0.860 and 0.884, respectively. The open database may have further uses in the diagnosis and management of patients with COVID-19.
Abstract 14156: Automated Electronic Medical Record Mapping to Identify Acute Precipitants of Atrial Fibrillation and Oral Anticoagulation Use
Authors: Mayank Sardana, Qiming Shi, Connor Saleeba, Tenes Paul, Alok Kapoor, Ziyue Wang, Steven A Lubitz, David McManus
Journal: Circulation (2020)

Introduction: Atrial fibrillation (AF) that is associated with acute precipitants frequently recurs and is associated with long-term morbidity and mortality. Leveraging a large electronic medical record (EMR) database, we previously reported the performance of an automated EMR-based algorithm to identify the acute precipitants of newly detected-AF, but its validation in other databases has not been performed. Hypothesis: Modified EMR-based algorithm would accurately identify acute precipitants of AF and oral anticoagulation (OAC) use after AF diagnosis Methods: Among all records (inpatient/outpatient/ER) in a single-institution EMR (10/1/17 - 12/31/19), we first identified 4493 records documenting newly-diagnosed AF (ICD 10: I48). We then applied the modified EMR-based algorithm to identify 13 acute AF precipitants (within 30 days of AF diagnosis, Figure 1) and determine OAC use after an AF diagnosis. We manually adjudicated a random subset of identified records (892 of 4493) to derive performance metrics of the EMR algorithm. Results: Of 4493 records with newly-diagnosed AF, the algorithm identified ≥1 acute precipitant in 831 records and ≥2 precipitants in 206 records. The most common precipitants were respiratory failure (38%) and pneumonia (35%). Among patients with CHADS2Vasc ≥2, 44% with an acute precipitant were prescribed an OAC vs. 63% free from a precipitant after initial AF diagnosis. EMR algorithm accurately identified the precipitants and OAC use after AF diagnosis (PPV 89% for both, Figure 1). Conclusions: In this validation study, our novel EMR-based automated algorithm was highly accurate at identifying acute precipitants of AF and OAC use after AF diagnosis. We also observed differential rates of OAC use between those with and without an acute precipitant. Application of the algorithm to multi-institutional datasets could help map the gaps in care (e.g., OAC use) AF patients with acute precipitants often experience.
A valve-in-valve transcatheter aortic valve implantation with commissural alignment using advanced imaging reconstruction: a case report
Authors: Marco Angelillis
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Transcatheter valve in valve (ViV) implantation actually represents a valid alternative to surgical reinterventions in patients with previous surgical aortic valve replacement (AVR). In patients less than 80 years old, it is crucial to correctly position the new valve leaving a feasible and easy access to coronary ostia, both for future percutaneous coronary intervention (PCI) than for a future possible TAVinTAV procedure. We report a 71 year old man with prior AVR presented with structural valve deterioration (SVD) leading to severe aortic stenosis. In order to guarantee comfortable coronary access we aligned, the commissures of the new percutaneous valve with the ones of the surgical bioprothesis by reconstructing the headframes of the surgical bioprosthesis with computer tomography (CT) and fluoro-CT.
Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma
Authors: Georgia M Beasley, Smita K Nair, Norma E Farrow, Karenia Landa, Maria Angelica Selim, Carol Ann Wiggs, Sin-Ho Jung, Darell D Bigner, Andrea True Kelly, Matthias Gromeier, April KS Salama
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background While programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) antagonists have improved the prognosis for many patients with melanoma, around 60% fail therapy. PVSRIPO is a non-neurovirulent rhinovirus:poliovirus chimera that facilitates an antitumor immune response following cell entry via the poliovirus receptor CD155, which is expressed on tumor and antigen-presenting cells. Preclinical studies show that oncolytic virus plus anti-PD-1 therapy leads to a greater antitumor response than either agent alone, warranting clinical investigation. Methods An open-label phase I trial of intratumoral PVSRIPO in patients with unresectable melanoma (American Joint Committee on Cancer V.7 stage IIIB, IIIC, or IV) was performed. Eligible patients had disease progression on anti-PD-1 and V-raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen activated protein kinase kinase (MEK) inhibitors (if BRAF mutant). The primary objective was to characterize the safety and tolerability of PVSRIPO. Twelve patients in four cohorts received a total of 1, 2 or 3 injections of PVSRIPO monotherapy, with 21 days between injections. Results PVSRIPO injections were well tolerated with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) reported. All adverse events (AEs) were grade (G) 1 or G2 (G1 pruritus most common at 58%); all but two PVSRIPO-treatment related AEs were localized to the injected or adjacent lesions (n=1 G1 hot flash, n=1 G1 fatigue). Four out of 12 patients (33%) achieved an objective response per immune-related response criteria (two observations, 4 weeks apart), including 4/6 (67%) who received three injections. In the four patients with in-transit disease, a pathological complete response (pCR) was observed in two (50%) patients. Following study completion, 11/12 patients (92%) reinitiated immune checkpoint inhibitor-based therapy, and 6/12 patients (50%) remained without progression at a median follow-up time of 18 months. Conclusion Intratumoral PVSRIPO was well tolerated. Despite the limited number of PVSRIPO treatments relative to the overall lesion burden (67% patients&gt;5 lesions), intratumoral PVSRIPO showed promising antitumor activity, with pCR in injected as well as non-injected lesions in select patients. Trial registration number NCT03712358
Worsening renal function after diuresis among heart failure patients with preserved ejection fraction: a dilemma to heart failure management. Letter regarding the article ‘Association of left ventricular ejection fraction with worsening renal function in patients with acute heart failure: insights from the RELAX‐AHF‐2 study’
Authors: John L. Starwalt, Amy F. Ho, Hao Wang
Journal: European Journal of Heart Failure (2020)
Abstract 161: African Ancestry and Blood Pressure Response Among African Americans in the Systolic Blood Pressure Reduction Intervention Trial
Authors: Shreya Rao, Matthew W Segar, Kershaw Patel, Ambarish Pandey
Journal: Circulation (2020)

Introduction: African ancestry (AA) is associated with higher BP prevalence, however the association of AA with response to intensive BP therapy, kidney function changes, and CV outcomes has not previously been explored. Methods: The study included participants from the SPRINT trial with available AA proportion. AA proportion was estimated using 106 biallelic genotype markers. Participants were stratified into tertiles from lowest (T1) to highest (T3) AA percentage. Time-dependent changes in SBP and eGFR were assessed by linear mixed-effect modeling after adjustment for potential confounders. Multivariable Cox models were constructed to evaluate the association of AA with risk of composite CV events (non-fatal MI, CV death, and HF event). Results: Among 2479 participants (median AA 78% [IQR: 73-87%], age 62 y, 46% female), baseline BP was similar across tertiles. At baseline, the prevalence of average Framingham CV risk (T1 vs. T2 vs. T3: mean 18.2% vs. 17.3% vs. 16.7%, p=0.01) and eGFR decreased (78 vs. 77 vs. 74, p=0.003) across increasing tertiles of AA. In contrast, the burden of DM (1.4% vs. 1.2% vs. 2.7%, p=0.05) and LV hypertrophy by EKG increased across increasing AA tertiles (11.1% vs. 12.0% vs. 15.7%, p=0.02). On follow up, the decline in BP over time was consistent across AA tertiles (mean reduction in SBP: 10 vs. 7 vs. 11 mm Hg, p=0.19) with no treatment interaction by genetic ancestry (p-int=0.60, Fig. A ). However, there was a greater decline in kidney function over time from T3 vs. T1 (mean eGFR decline = 3.8, 3.3, and 5.0 in T1-3) ( Fig. B ). The risk of adverse CV event was not different across AA tertiles [adjusted HR (95% CI): T3 vs. T1 = 0.93 (0.61-1.44); T2 vs T1 = 0.69 (0.42-1.11)]. Conclusions: Genetic AA was not significantly associated with baseline BP level or response to therapy in the SPRINT trial. Higher genetic African ancestry was associated with favorable CV risk profiles with no difference in adverse CV event risk, but greater decline in renal function over time.
Abstract 14618: Bicuspid Aortic Valve Morphology and Risk Factors of Abnormal Hemodynamics: An Experimental Investigation of Velocity, Vorticity and Eccentricity of Systolic Jet Stream, Using a Magnetic Resonance Imaging Compatible Pulsatile Flow Circulation System
Authors: Kaoru Hattori, Natsuki Nakama, Jumpei Takada, Gohki Nishimura, Ryo Moriwaki, Eita Kawasaki, Michinobu Nagao, Yasuhiro Goto, Hiroshi Niinami, Kiyotaka Iwasaki
Journal: Circulation (2020)

Introduction: Abnormal hemodynamics with bicuspid aortic valve (BAV) is influenced by the BAV morphology. However, due to the morphological variety, the relationship between BAV morphology and hemodynamics has not been well clarified. We experimentally investigated influences of BAV morphology on hemodynamics. Methods: An MRI compatible pulsatile flow circulation system incorporating an aortic valve model and morphologically relevant aortic arch model was developed. Two types of BAV models with cusp angles of 240-120 (asymmetric BAV) and 180-180 (symmetric BAV) were prepared using bovine aorta and pericardium. The vorticity and eccentricity of jet in the aortic arch model in systolic phase were assessed using 4D-flow MRI. Streamlines at peak systole were compared among 5 BAV morphologies defined based on the symmetry and the position of leaflets (Fig). Results: Eccentric supra-valvular jets directed to the aortic wall faced to the smaller leaflet were present in the 3 asymmetric BAVs. In the ABAV-1, a markedly eccentric jet impinging on the aortic outer curvature was present. In the ABAV-2, a left-posterior directed jet shifting to the outer curvature of proximal arch was present. The asymmetric BAVs induced larger flow vorticity in the ascending aorta than the symmetric BAVs (ABAV-1 vs -2 vs -3 vs SBAV-1 vs -2, 0.018 vs 0.019 vs 0.014 vs 0.010 vs 0.011 m 2 /s). The ABAV-2 had a larger vortex in the middle arch than the ABAV-1 (ABAV-2 vs -1, 0.010 vs 0.005 m 2 /s). Conclusion: Our study indicated that the angles and orientations of the BAV impacted on the locations of jets impinging on the aortic wall and magnitudes of vorticities in systole. In the asymmetric BAVs, the direction of jet was influenced by the position of smaller leaflet. Our data suggests that the ABAV-1 morphology may be a risk factor inducing asymmetric aneurysm bulged toward the aortic outer curvature, while the ABAV-2 morphology may be a risk factor of an aortic aneurysm involving the transvers arch.
Abstract 13135: Starting Beta-blockers in Hypertension is Followed by Excess Loop Diuretic Use: Beta-blocker Induced Heart Failure?
Authors: Daniel N Silverman, Jeanne d de Lavallaz, Timothy B Plante, Margaret M Infeld, Markus Meyer
Journal: Circulation (2020)

Introduction: Recent investigation has identified that discontinuation of beta-blockers in subjects with normal left ventricular ejection fraction (LVEF) leads to a reduction in natriuretic peptide levels. We investigated whether a similar trend would be seen in a hypertension clinical trial cohort. Methods: In 9,012 subjects hypertensive subjects without a history of symptomatic heart failure, known LVEF &lt;35% or recent heart failure hospitalization enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT), we compared incidence of loop diuretic initiation and time to initiation following start of a new anti-hypertensive medication. The categorical relationship (new antihypertensive class followed by loop-diuretic use) and temporal relationship (time to loop diuretic initiation) were each analyzed. The categorical relationship was assessed using a Pearson’s chi-squared test and the temporal relationship using a Wilcoxon rank sum test. Bonferroni-corrected p-values were utilized for all comparisons. Results: Among the 9,012 subjects analyzed, the incidence of anti-hypertensive initiation and loop diuretic initiation was greatest following start of a beta-blocker (16.6%) compared with other antihypertensive medication classes (calcium channel blocker 13.8%, angiotensin converting enzyme-inhibitor/angiotensin receptor blocker 12.9% and thiazide diuretic 10.2%; p&lt;0.001). In addition, the median time between starting a new antihypertensive medication and loop diuretic was the shortest for beta-blockers and longest for thiazides (both p &lt;0.01). No significant differences in renal function were identified between groups. Conclusion: Compared to other major classes of hypertensive agents, starting beta-blockers was associated with more common and earlier initiation of a loop diuretics in a population without heart failure at baseline. This finding may suggest beta-blocker induced heart failure in a population with a predominantly normal ejection fraction.
Abstract 16768: Improving Detection and Diagnosis of Rheumatic Fever in Low Resource Settings
Authors: Emma Ndagire, Pulle Jafesi, Linda Oyella, JENIFER ATALA, Rachel Sarnacki, Emmy Okello, Nicholas Ollberding, Laurie Smith, Craig A SABLE, Andrea Z Beaton
Journal: Circulation (2020)

Introduction: Acute rheumatic fever (ARF) remains under diagnosed in low resource settings yet it is associated with dire consequences. Application of Jones criteria, the standard criteria used for diagnosis of ARF in these settings is challenging as many of its features are not readily available. Objective: To determine the performance of readily available information at each level of the healthcare system in Uganda, to determine the sensitivity and specificity of ARF diagnosis in resource limited settings. Methods: Variables that might positively or negatively predict ARF based on typical diagnostic capacity at 3 tiers of Uganda’s health system (community health center, district hospital, and national referral) were selected from a large epidemiological study conducted in northern and central Uganda. These variables were put into three statistical models to determine those that were associated with the disease. Model 1 included those variables commonly found at community health centers (features from history and clinical exam), the second model included all variables from the first model plus laboratory tests that are sometimes available (malaria antigen test, complete blood count and EKG) while the 3 rd model comprised of all variables from the 2 nd model and advanced tests that are not commonly available (ASO titers, acute phase reactants and echocardiography).Youden’s index was used to calculate sensitivity and specificity of the models and ROC curves plotted. Results: Presence of visible joint swelling and heart murmur were associated with ARF in the first and second models while carditis on echocardiogram had the highest odds ratios in the 3 rd model. Sensitivity and specificity for ARF were (51.3%, 81.0%), (60.5%, 84%) and (79.8%, 92.5%) for model 1, 2 and 3 respectively. Conclusions: Our data supports the importance of including echocardiography for the diagnosis of carditis in Jones criteria for ARF. At the same time, Jones criteria are not practical in endemic settings that not have access to definitive diagnostic testing. A new approach that is appropriate for endemic regions is therefore needed.