tbuckley/cabot-search huggingface dataset:
Hope Shattered, Hope Restored
Authors: Andrea M. Watson
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Abstract 14710: Cardiovascular Interventions in Face of Covid-19 Pandemic in a Low to Middle Income Country of South Asia Region - <i>A Pre and Post Covid Era Comparison!</i>
Authors: Pirbhat Shams, Osman Faheem, ghufran adnan, Jamshed Ali, Maria Khan
Journal: Circulation (2020)

Introduction: Worldwide, cardiologists have reported decline in cardiac catheterization lab (CCL) activation. In this study, we analysed the impact of COVID19 outbreak on cardiology intervention in a tertiary care centre of epicentre of Pakistan. Methods: A retrospective study was conducted on patients admitted via emergency department (ED) and undergoing cardiovascular intervention. Data for CCL procedures was obtained from electronic register for March-April 2019 (pre-COVID era - pCE) and March-April 2020 (COVID era - CE). Comparison was made between the two era for number of times CCL was activated with regard to left heart catheterization (LHC), percutaneous coronary intervention (PCI) or cardiac implantable electronic devices (CIED). This study also compared numbers for coronary artery bypass grafting (CABG) and cardiac imaging. Results: A total of 239 and 106 patients were admitted via ED in pCE and CE respectively (Reduction =R=55.6%). Total procedures performed dropped from 183 to 73 (R = 60.11%). Numbers for primary PCI were 34 (pCE) and 16 (CE) with R = 52.94%. 41 patients underwent LHC in pCE in comparison to 13 patients in CE (R = 68.29%). PCI other than primary was performed in 30 (pCE) and 24 patients (CE) with R = 20%. CABG numbered to 26 (pCE) and 12 (CE) with R = 53.85%. CIED was implanted in 12 and 2 patients in pCE and CE respectively (R = 83.33%). Additionally cardiac imaging modality was used in 38 (pCE) and 6 patients (CE) with R = 84.21 %. Conclusion: There is significant reduction in rate of primary PCI, LHC, CABG, CIED and non-invasive imaging procedures during CE. South-asia region carries huge burden of undiagnosed cardiovascular disease. Significant drop in cardiovascular procedure in CE is alarming and warns us for need of preparedness for times of increased late presentations or cardiovascular morbidity or mortality. This highlights the importance of urging public to report for their cardiac symptoms in face of COVID-19 pandemic.
The Early Evolution of Oral Poliovirus Vaccine Is Shaped by Strong Positive Selection and Tight Transmission Bottlenecks
Authors: Andrew L. Valesano, Mami Taniuchi, William J. Fitzsimmons, Md Ohedul Islam, Tahmina Ahmed, Khalequ Zaman, Rashidul Haque, Wesley Wong, Michael Famulare, Adam S. Lauring
Journal: Cell Host & Microbe (2020)

The emergence of circulating vaccine-derived polioviruses through evolution of the oral polio vaccine (OPV) poses a significant obstacle to polio eradication. Understanding the early genetic changes that occur as OPV evolves and transmits is important for preventing future outbreaks. Here, we use deep sequencing to define the evolutionary trajectories of type 2 OPV in a vaccine trial. By sequencing 497 longitudinal stool samples from 271 OPV2 recipients and household contacts, we were able to examine the extent of convergent evolution in vaccinated individuals and the amount of viral diversity that is transmitted. In addition to rapid reversion of key attenuating mutations, we identify strong selection at 19 sites across the genome. We find that a tight transmission bottleneck limits the onward transmission of these early adaptive mutations. Our results highlight the distinct evolutionary dynamics of live attenuated virus vaccines and have important implications for the success of next-generation OPV.
Abstract 14304: Assessing the Association of Adherence to Fractional Flow Reserve Treatment Thresholds and Outcomes of Patients With Coronary Artery Disease
Authors: Maneesh Sud, Lu Han, Maria Koh, Peter Austin, Michael E Farkouh, Hung Ly, Mina Madan, Madhu K Natarajan, Derek Y So, Harindra C Wijeysundera, Dennis T Ko
Journal: Circulation (2020)

Background: Although fractional flow reserve (FFR) thresholds have been established to guide the use of percutaneous coronary intervention (PCI) or medical therapy, little is known about the adherence to FFR thresholds for PCI in clinical practice and their association with clinical outcomes. Methods: Adults undergoing FFR assessment in a single vessel (excluding ST-segment elevation myocardial infarction [MI]) from April 1, 2013 to March 31, 2018 in Ontario, Canada were included. Patients were divided into two cohorts based on FFR ≤ 0.80 (ischemic) and &gt; 0.80 (non-ischemic). Inverse probability of treatment weighting was used to balance confounders between patients treated with PCI vs. no PCI in each cohort. The primary outcome was major adverse cardiac events (MACE) defined by death, MI, unstable angina, or urgent revascularization. Results: We identified 9,106 patients who underwent single-vessel FFR measurement. Among the 2,693 patients with an ischemic FFR (mean age 65, 27.0% female), 75.3% of patients received PCI and 24.7% were treated only with medical therapy. Over a median follow-up of 2.6 years in the ischemic cohort, PCI was associated with a 20% lower rate of MACE compared to no PCI (24.0% vs. 31.6%; hazard ratio [HR]: 0.80, 95% CI: 0.66-0.96). However, among 6,413 patients with a non-ischemic FFR (mean age 66, 38.9% female), 12.6% received PCI and 87.4% were treated only with medical therapy. Over a median follow-up of 2.8 years in the non-ischemic cohort, PCI was associated with a 42% higher rate of MACE compared to no PCI (25.6% vs. 17.6%; HR: 1.42, 95% CI: 1.18-1.70). The increased rate of MACE was driven mainly by MI (HR 1.67, 95% CI: 1.20-2.31) but not death (HR 0.99, 95% CI: 0.72-1.35). Conclusions: In routine practice, we found 1 in 4 patients did not receive PCI for ischemic lesions while 1 in 8 received PCI for non-ischemic lesions. Performing PCI procedures according to recommended FFR cutoffs was associated with lower rates of clinical events.
Association of Prenatal Exposure to Valproate and Other Antiepileptic Drugs With Intellectual Disability and Delayed Childhood Milestones
Authors: Christine Aarenstrup Daugaard, Lars Pedersen, Yuelian Sun, Julie Werenberg Dreier, Jakob Christensen
Journal: JAMA Network Open (2020)

There is concern about neurodevelopmental outcomes associated with prenatal exposure to valproate and other antiepileptic drugs (AEDs) among children of mothers with or without epilepsy.To study the risk of intellectual disability and delayed development in childhood milestones among children of women who used valproate or other AEDs during pregnancy.This population-based cohort study analyzed information on use of AEDs from the Danish National Prescription Registry and register diagnoses from the Danish Psychiatric Central Research Register and Danish National Patient Registry. The study included all live-born singletons in Denmark from January 1, 1997, to December 31, 2011. Data were analyzed in April 2020.Prenatal exposure to maternal valproate and other AEDs.The main measures were adjusted Cox regression estimates of hazard ratios (aHRs) for intellectual disability and a combined outcome of intellectual disability with delayed childhood milestones.A total of 913 302 children (468 708 [51.3%] boys; mean [SD] age, 10.3 [4.4] years and median [interquartile range] age, 10.1 [6.5-14.0] years at final follow-up) were identified and contributed more than 10.2 million person-years of observation, including 580 children exposed to valproate (302 [51.3%] boys). At end of follow-up, 6958 children (0.8%) were identified as having intellectual disability and 14 967 children (1.6%) were identified as having intellectual disability with delayed childhood milestones. Compared with offspring not exposed to valproate prenatally, offspring of women who used valproate during pregnancy had increased risk of intellectual disability (aHR, 4.48; 95% CI, 2.97-6.76) and intellectual disability with delayed childhood milestones (aHR, 6.07; 95% CI, 4.67-7.89). Among mothers with epilepsy, offspring exposed prenatally to valproate had increased risk of intellectual disability (aHR, 1.95; 95% CI, 1.21-3.14) and intellectual disability with delayed childhood milestones (aHR, 3.07; 95% CI, 2.24-4.20) compared with offspring without prenatal exposure. Compared with offspring without prenatal exposure to AEDs, increased risk of intellectual disability was identified in children with prenatal exposure to maternal monotherapy use of carbamazepine (aHR, 3.84; 95% CI, 2.32-6.38), clonazepam (aHR, 2.41; 95% CI, 1.09-5.35), and oxcarbazepine (aHR, 3.70; 95% CI, 2.11-6.51) but not lamotrigine (aHR, 1.33; 95% CI, 0.71-2.48).These findings suggest that prenatal exposure to valproate was associated with increased risk of intellectual disability and delayed childhood milestones. Statistically significant associations were also found for prenatal exposure to other AEDs. These findings suggest that women of childbearing potential may need to be counseled on use of AEDs.
Abstract 13832: Cardiac Mesenchymal Cells (CMCs) Cultured at Physiologic Oxygen Tension Have Superior Therapeutic Efficacy in Mice With Heart Failure Caused by Myocardial Infarction
Authors: Robi Bolli, Chandrashekhar Dasari, Amr Alkasir, Asma Arshia, Yibing Nong, Yiru Guo, Usman Ashraf, Qianhong Li
Journal: Circulation (2020)

Stem/progenitor cells are usually cultured at atmospheric O 2 tension (21%); however, since physiologic O 2 tension in the heart is ~5%, using 21% O 2 may cause oxidative stress and toxicity. CMCs, a newly-discovered and promising type of progenitor cells, are effective in improving LV function after myocardial infarction (MI). To determine if 5% O 2 enhances therapeutic efficacy of CMCs, murine CMCs were cultured at 21% or 5% O 2 . Compared with 21% O 2 , culture at 5% O 2 significantly ( P &lt;0.001) increased cell proliferation, telomerase activity, telomere length, and resistance to severe hypoxia (1% O 2 for 24 h) in vitro . Then, LV dysfunction was produced in 48 mice by a 60 min MI; 30 days later, mice received vehicle or CMCs cultured at 21% O 2 or 5% O 2 . After 35 days, the improvement in LV ejection fraction effected by 5% O 2 CMCs was &gt;3 times greater than by 21% O 2 CMCs (5.2 vs. 1.5 units, P &lt;0.01) (Figs. A-B). Hemodynamic studies (Millar catheter) yielded similar results both for load-dependent (LV dP/dt) and load-independent (end-systolic elastance) indices (Figs. C-D). Thus, 2 independent methods (echo and hemodynamics) demonstrated that compared with 21% O 2 , using 5% O 2 to culture CMCs results in greater functional improvement in the failing heart. Further, 5% O 2 CMCs produced greater reduction in myocardial fibrosis and exhibited much longer survival after transplantation ( P &lt;0.01 for both). In conclusion, culturing CMCs at physiologic (5%) O 2 tension results in more rapid proliferation (reducing time and cost to achieve target cell numbers), less senescence, greater resistance to severe hypoxia (making cells better able to survive in scarred regions where O 2 is very low [1-2%]), and superior therapeutic efficacy in promoting cardiac repair after MI. Thus far, almost all preclinical and clinical studies of cell therapy have used 21% O 2 to culture cells. Our data challenge this paradigm and support the need to change the methods used to culture CMCs and possibly other progenitor cells.
NHS should vary price it pays for cancer drugs to improve access, say experts
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The NHS should vary the price it pays for cancer drugs depending on the disease they are used to treat, a group of experts has concluded.

New pricing models could widen patient access to new cancer treatments, the panel of academic and industry experts advised. The government should also consider tying prices of cancer drugs to the benefits they deliver for patients, they said.

The recommendations were drawn up after a summit held by the Institute of Cancer Research, London. The panel consisted of 16 academic institutions, charities, stakeholder groups, and drug companies (see box).

The group recommends that …
Association of Skilled Nursing Facility Participation in a Bundled Payment Model With Institutional Spending for Joint Replacement Surgery
Authors: Michael L. Barnett, Karen E. Joynt Maddox, E. John Orav, David C. Grabowski, Arnold M. Epstein
Journal: JAMA (2020)

Medicare recently concluded a national voluntary payment demonstration, Bundled Payments for Care Improvement (BPCI) model 3, in which skilled nursing facilities (SNFs) assumed accountability for patients' Medicare spending for 90 days from initial SNF admission. There is little evidence on outcomes associated with this novel payment model.
Abstract 133: Association of End Tidal Carbon Dioxide &gt;20mmhg with Pediatric In-hospital Cardiac Arrest Quality of Cpr and Survival
Authors: Priscilla Yu, Robert M Sutton, Richard Hanna, Xuemei Zhang, Heather M Griffis, Dana E Niles, Robert A Berg, Andrea Christoff, Jimena del Castillo, Takanari Ikeyama, Jonathan Gilleland, Kamal Abulebda, Tia T Raymond, Vinay M Nadkarni
Journal: Circulation (2020)

Introduction: AHA recommends titrating chest compressions (CC) to achieve end-tidal carbon dioxide (ETCO2)&gt;20mmHg, based on laboratory, adult, and very limited pediatric IHCA data. Hypothesis: ETCO2&gt;20mmHg averaged during the first 10 min of recorded CPR is associated with 1) compliance with AHA CC depth quality targets, and 2) survival to hospital discharge. Methods: All pediatric 2015-2019 IHCA events reported by 4 pediRES-Q sites with simultaneous ETCO2 and CC metrics (ZOLL R-Series defibrillator) measured. Analysis included the first 10 min of CPR with CC data recorded using dual sensor accelerometers that compensate for mattress deflection. Compliance with 2015 AHA guidelines CC depth quality target defined as ∼1/3 estimated AP diameter: ≥3.4 cm for infants &lt;1yr, ≥4.4cm for 1 to &lt; 8yrs, and 4.5-6.6cm for 8 to ≤ 18yrs. Primary analysis for ETCO2&gt;20mmHg cutoff association with CC depth and survival by modified Poisson regression models, accounting for age. Secondary analysis for mean ETCO2 (no a priori cutoff) association with CC depth and survival, adjusting for age. Results: Of 44 events (24 index): median 10-min averaged ETCO2 was 23 [IQR 13, 37] mmHg, CPR duration was 23 [IQR 10, 53] min, return of spontaneous circulation (ROSC) was 70% (31/44), and survival to hospital discharge was 33% (8/24). ETCO2&gt;20 mmHg cutoff was associated with CC depth [RR 1.55 (95%CI: 1.20,2.00) p=0.0007], and age-specific AHA depth quality target compliance [RR 1.01 (95%CI: 1.00,1.02) p=0.02. However, ETCO2 &gt; 20mmHg cutoff was not significantly associated with survival: ROSC [RR 1.08 (95%CI: 0.71, 1.65), p=0.72)] nor survival to hospital discharge [RR 1.10 (95%CI: 0.33, 3.65), p=0.87]. Mean 10-min averaged ETCO2 (no cutoff) was not significantly associated with CC depth (p=0.09), age-specific AHA depth quality target compliance (p=0.07), ROSC (p=0.57) , nor survival to hospital discharge (26 [IQR 14, 43] mmHg vs. 16 [IQR 13,34] mmHg non-survival to hospital discharge, p=0.28). Conclusions: In this multicenter pediatric In-hospital CPR cohort, ETCO2&gt;20mmHg cutoff averaged during the first 10-min of recorded CPR was significantly associated with CC depth and age-specific AHA depth quality target compliance, but not with ROSC or survival to hospital discharge.
Abstract 13656: Outcomes of Pre-existing Cardiovascular Disease Amongst COVID-19 Patients
Authors: Chail Shah, Harmandeep Singh, Mehwish Martin, Salma Yousuf, Payu Raval, Nirmaljot Kaur, Chika Nwodika, Angelina Yogarajah, Rashmi Subhedar, Jigisha Rakholiya, Urvish K Patel
Journal: Circulation (2020)

Introduction: COVID-19 has multiorgan involvement and it is believed that outcomes are poor amongst patients with hypertension (HTN) and pre-existing cardiovascular disorders (CVD). Hypothesis: The objective of this meta-analysis is to evaluate outcomes [mortality and invasive mechanical ventilation (IMV) utilization] of COVID-19 in patients with pre-existing HTN and CVD. Methods: English full-text-observational studies having data on epidemiological characteristics of patients with COVID-19 were identified searching PubMed using MeSH-terms from December 1, 2019, to April 30, 2020. Studies having CVD or HTN as one of the pre-existing comorbidities and described outcomes including IMV and mortality were selected with a consensus of three reviewers. 29 studies met these criteria. Following MOOSE protocol, data on patients’ characteristics especially age and history of CVD, HTN, IMV, and mortality were pooled using a random-effects model. The pooled prevalence of CVD and HTN were calculated. Meta-regression was performed and correlation coefficient (r) and odds ratio (OR) were estimated to evaluate the effects of pre-existing CVD and HTN on outcomes of COVID-19 patients. Results: Out of 29 studies with COVID-19 epidemiology data, 21, 17, 18 and 19 studies have details on mortality, IMV, HTN, and pre-existing CVD, respectively. Pooled prevalence of HTN was 28.2% [95%CI:22.1%-35.1%; p&lt;0.001; 4858/11626 patients; Heterogeneity (I 2 ):97.8%] and pre-existing CVD was 12.2% [8.9%-16.6%; p&lt;0.001; 2044/11664 patients; I 2 :96.8%]. In age-adjusted meta-regression analysis, IMV was significantly higher among COVID-19 patients with pre-existing CVD [r:0.28; OR:1.3 (1.1-1.6); I 2 :89.7%; p=0.0028] without significant association with HTN [r:0.01; OR:1.0 (0.9-1.1); I 2 :95.9%; p=0.8161]. HTN [r:0.001; OR:1.0 (0.9-1.1); I 2 :96%; p=0.9685] and pre-existing CVD [r:-0.01; OR:0.9 (0.9-1.1); I 2 :96.3%; p=0.8772] had no significant association with mortality amongst COVID-19 patients. Conclusion: In the age-adjusted analysis, though we identified pre-existing CVD as a risk factor for higher utilization of IMV, pre-existing CVD and HTN had no independent role in increasing mortality.
Association of Genetic West African Ancestry, Blood Pressure Response to Therapy, and Cardiovascular Risk Among Self-reported Black Individuals in the Systolic Blood Pressure Reduction Intervention Trial (SPRINT)
Authors: Shreya Rao, Matthew W. Segar, Adam P. Bress, Pankaj Arora, Wanpen Vongpatanasin, Vijay Agusala, Utibe R. Essien, Adolfo Correa, Alanna A. Morris, James A. de Lemos, Ambarish Pandey
Journal: JAMA Cardiology (2020)

Self-identified Black race is associated with higher hypertension prevalence and worse blood pressure (BP) control compared with other race/ethnic groups. The contribution of genetic West African ancestry to these racial disparities appears not to have been completely determined.
The Assessment of Different Diets and Mortality Fails to Address Unmeasured Confounding—Reply
Authors: Zhilei Shan, Frank B. Hu, Qibin Qi
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Vaccination with early ferroptotic cancer cells induces efficient antitumor immunity
Authors: Iuliia Efimova, Elena Catanzaro, Louis Van der Meeren, Victoria D Turubanova, Hamida Hammad, Tatiana A Mishchenko, Maria V Vedunova, Carmela Fimognari, Claus Bachert, Frauke Coppieters, Steve Lefever, Andre G Skirtach, Olga Krysko, Dmitri V Krysko
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immunotherapy represents the future of clinical cancer treatment. The type of cancer cell death determines the antitumor immune response and thereby contributes to the efficacy of anticancer therapy and long-term survival of patients. Induction of immunogenic apoptosis or necroptosis in cancer cells does activate antitumor immunity, but resistance to these cell death modalities is common. Therefore, it is of great importance to find other ways to kill tumor cells. Recently, ferroptosis has been identified as a novel, iron-dependent form of regulated cell death but whether ferroptotic cancer cells are immunogenic is unknown. Methods Ferroptotic cell death in murine fibrosarcoma MCA205 or glioma GL261 cells was induced by RAS-selective lethal 3 and ferroptosis was analyzed by flow cytometry, atomic force and confocal microscopy. ATP and high-mobility group box 1 (HMGB1) release were detected by luminescence and ELISA assays, respectively. Immunogenicity in vitro was analyzed by coculturing of ferroptotic cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of phagocytosis and activation/maturation of BMDCs (CD11c + CD86 + , CD11c + CD40 + , CD11c + MHCII + , IL-6, RNAseq analysis). The tumor prophylactic vaccination model in immune-competent and immune compromised (Rag-2 −/− ) mice was used to analyze ferroptosis immunogenicity. Results Ferroptosis can be induced in cancer cells by inhibition of glutathione peroxidase 4, as evidenced by confocal and atomic force microscopy and inhibitors’ analysis. We demonstrate for the first time that ferroptosis is immunogenic in vitro and in vivo. Early, but not late, ferroptotic cells promote the phenotypic maturation of BMDCs and elicit a vaccination-like effect in immune-competent mice but not in Rag-2 −/− mice, suggesting that the mechanism of immunogenicity is very tightly regulated by the adaptive immune system and is time dependent. Also, ATP and HMGB1, the best-characterized damage-associated molecular patterns involved in immunogenic cell death, have proven to be passively released along the timeline of ferroptosis and act as immunogenic signal associated with the immunogenicity of early ferroptotic cancer cells. Conclusions These results pave the way for the development of new therapeutic strategies for cancers based on induction of ferroptosis, and thus broadens the current concept of immunogenic cell death and opens the door for the development of new strategies in cancer immunotherapy.