tbuckley/cabot-search huggingface dataset:
Abstract P353: Paradoxical Secular Trends in Stroke and Hypertension Incidences among Men and Women in Rural Areas of China: Results from Two Population-based Cohorts
Authors: Liqiang Zheng, Yingxian Sun
Journal: Circulation (2018)

Background: Stroke has been the leading cause of death in China and hypertension accounts for about one-third of deaths due to stroke in Chinese adults. The current study aimed to examine the secular trends of stroke and hypertension in two population-based samples. Methods: The study included three cohorts (2004-2008, n=38,949; 2008-2010, n=38,264; and 2013-2016, n=8,880) from two population-based studies: Fuxin Cardiovascular Cohort Study (FCCS) and Northeast China Rural Cardiovascular Health Study (NCRCHS). Results: There was a significant increasing trend for incidence of stroke in both men and women ( P for trend &lt;0.001). The age-adjusted incidence of stroke (per 100,000 person-years) among the 3 Cohorts was 575.3, 893.0, and 1382.7 in men and 358.9, 456.5, and 1046.2 in women, respectively. With the 2004 Cohort as the reference group, we observed a 52.9% increase in 2008-2010 and a 169.9% increase in 2013-2016 among men. However, hypertension incidence decreased steeply in both sexes from 2004-2008 (15.2 in men and 12.6 in women per 100 person-years) to 2013-2016 (9.6 in men and 7.1 in women per 100 person-years) ( P for trend &lt;0.0001). Conclusions: Incidence of stroke has increased and incidence of hypertension decreased since 2004, which has implications for prevention of both diseases in China.
Inherited human IFN-γ deficiency underlies mycobacterial disease
Authors: Gaspard Kerner, Jérémie Rosain, Antoine Guérin, Ahmad Al-Khabaz, Carmen Oleaga-Quintas, Franck Rapaport, Michel J. Massaad, Jing-Ya Ding, Taushif Khan, Fatima Al Ali, Mahbuba Rahman, Caroline Deswarte, Rubén Martinez-Barricarte, Raif S. Geha, Valentine Jeanne-Julien, Diane Garcia, Chih-Yu Chi, Rui Yang, Manon Roynard, Bernhard Fleckenstein, Flore Rozenberg, Stéphanie Boisson-Dupuis, Cheng-Lung Ku, Yoann Seeleuthner, Vivien Béziat, Nico Marr, Laurent Abel, Waleed Al-Herz, Jean-Laurent Casanova, Jacinta Bustamante
Journal: Journal of Clinical Investigation (2020)

Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by a selective predisposition to clinical disease caused by the Bacille Calmette-Guérin (BCG) vaccine and environmental mycobacteria. The known genetic etiologies of MSMD are inborn errors of IFN-γ immunity due to mutations of 15 genes controlling the production of or response to IFN-γ. Since the first MSMD-causing mutations were reported in 1996, biallelic mutations in the genes encoding IFN-γ receptor 1 (IFN-γR1) and IFN-γR2 have been reported in many patients of diverse ancestries. Surprisingly, mutations of the gene encoding the IFN-γ cytokine itself have not been reported, raising the remote possibility that there might be other agonists of the IFN-γ receptor. We describe 2 Lebanese cousins with MSMD, living in Kuwait, who are both homozygous for a small deletion within the IFNG gene (c.354_357del), causing a frameshift that generates a premature stop codon (p.T119Ifs4*). The mutant allele is loss of expression and loss of function. We also show that the patients' herpesvirus Saimiri-immortalized T lymphocytes did not produce IFN-γ, a phenotype that can be rescued by retrotransduction with WT IFNG cDNA. The blood T and NK lymphocytes from these patients also failed to produce and secrete detectable amounts of IFN-γ. Finally, we show that human IFNG has evolved under stronger negative selection than IFNGR1 or IFNGR2, suggesting that it is less tolerant to heterozygous deleterious mutations than IFNGR1 or IFNGR2. This may account for the rarity of patients with autosomal-recessive, complete IFN-γ deficiency relative to patients with complete IFN-γR1 and IFN-γR2 deficiencies.
Covid-19: Doctors warn of humanitarian catastrophe at Europe’s largest refugee camp
Authors: Gareth Iacobucci
Journal: BMJ (2020)

A UK based charity that provides healthcare to residents at Europe’s largest refugee camp has warned that overcrowding could prompt a humanitarian catastrophe in the wake of the covid-19 pandemic.

Siyana Marhroof Shaffi, director of the UK based charity Kitrinos Healthcare, which runs a medical clinic on the island of Lesvos, Greece, warned of an “alarming” risk to thousands of vulnerable refugees in the Moria camp.

The island’s first case of covid-19 was confirmed last week. Shaffi said that mitigation …
Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance
Authors: Chaochu Cui, Jianbo Yang, Xiao Li, Dongling Liu, Liwu Fu, Xianwei Wang
Journal: Molecular Cancer (2020)

Abstract Circular RNAs (circRNAs), one type of non-coding RNA, were initially misinterpreted as nonfunctional products of pre-mRNA mis-splicing. Currently, circRNAs have been proven to manipulate the functions of diverse molecules, including non-coding RNAs, mRNAs, DNAs and proteins, to regulate cell activities in physiology and pathology. Accumulating evidence indicates that circRNAs play critical roles in tumor genesis, development, and sensitivity to radiation and chemotherapy. Radiotherapy and chemotherapy are two primary types of intervention for most cancers, but their therapeutic efficacies are usually retarded by intrinsic and acquired resistance. Thus, it is urgent to develop new strategies to improve therapeutic responses. To achieve this, clarification of the underlying mechanisms affecting therapeutic responses in cancer is needed. This review summarizes recent progress and mechanisms of circRNAs in cancer resistance to radiation and chemotherapy, and it discusses the limitations of available knowledge and potential future directions.
Temporal Changes in Secondary Prevention and Cardiovascular Outcomes After Revascularization for Peripheral Arterial Disease in Denmark
Authors: Mette Søgaard, Peter Brønnum Nielsen, Flemming Skjøth, Nikolaj Eldrup, Torben Bjerregaard Larsen
Journal: Circulation (2020)

Background: Patients with peripheral arterial disease (PAD) are at increased risk of cardiovascular morbidity and mortality. Medical prevention with antithrombotic and statin therapies is a mainstay of treatment to prevent adverse outcomes; nevertheless, patients with PAD are often undertreated. This study describes the temporal changes in medical prevention and adverse outcomes in a national cohort of patients with symptomatic PAD after revascularization. Methods: We identified all patients with a first open surgical or endovascular revascularization procedure in the lower extremities or abdomen in Denmark, from 2000 to 2016. We examined temporal changes in the use of aspirin, clopidogrel, and statins and 1-year cause-specific hazard ratios for adverse clinical outcomes, after adjusting for procedure type, treatment indication, age, sex, and cardiovascular risk factors. The analyses were performed overall and within strata of index procedure (endovascular versus surgical), treatment indication, age, sex, and high-risk comorbidities. Results: Between 2000 and 2016, we identified 32 911 patients who underwent revascularization for symptomatic PAD. The mean age was 69 years and increased over time, as did the burden of comorbidity. The cumulative incidence of medication use increased between 2000 to 2004 and 2013 to 2016, respectively, from 57.3% to 64.3% for aspirin, 3.6% to 24.8% for clopidogrel, and 36.2% to 77.1% for statins. Concurrently, the 1-year outcome rates declined. Compared with 2000 to 2004, the adjusted hazard ratios in 2013 to 2016 were 0.73 (95% CI, 0.62–0.84) for major adverse cardiovascular events, 0.92 (95% CI, 0.85–1.00) for major adverse limb events, 0.60 (95% CI, 0.48–0.74) for myocardial infarction, 0.94 (95% CI, 0.75–1.18) for ischemic stroke, 0.92 (95% CI, 0.75–1.12) for major bleeding, 0.54 (95% CI, 0.39–0.76) for cardiovascular death, and 0.80 (95% CI, 0.72–0.88) for all-cause death. These improvements in prognosis were most prominent from 2000 to 2004 to 2005 to 2008 and occurred in all strata of index procedure, treatment indication, sex, age, and comorbidity. In contrast, the adjusted hazard ratio for major amputations was 1.00 (95% CI, 0.90–1.11) when comparing 2013 to 2016 to 2000 to 2004. Conclusions: Medical prevention of adverse events has increased considerably over time in patients who underwent revascularization for symptomatic PAD. This increase was accompanied by reductions in all adverse outcomes, except major amputations.
EGFR variant III expression in Chinese patients with non-small cell lung cancer.
Authors: Jie Wang, Jianchun Duan, Hua Bai, Lu Yang, Tongtong An, Zhijie Wang, Minglei Zhuo
Journal: Journal of Clinical Oncology (2012)

e18022 Background: Patients with advanced squamous cell lung carcinoma (SCC), even though harboring the EGFR mutation, showed an inferior response to EGFR-TKI. The aim of this retrospective study was to determine the clinicopathologic characteristics and distribution profiles of EGFRv III in Chinese NSCLC patients, and to explore the likely relationship between EGFRv III mRNA levels and the response to EGFR-TKI. Methods: Frozen tissues were retrospectively obtained from 114 NSCLC patients who received surgery resection and 13 advanced NSCLC patients who received EGFR-TKI treatment in Peking Universuty Cancer Hospital. EGFRv III expression was detected by RT-PCR and EGFR mutation was detected by denaturing high-performance liquid chromatography (DHPLC). The association between EGFRv III and clinicopathologic features was investigated by statistical analysis. Results: frequency of EGFRv III in 114 post-surgery NSCLC patients was 7.02% (8/114), including 11.11% (6/54) in SCC and 3.64% (2/55) in adenocarcinomas (ADC). The frequency of EGFRv III expression was higher in SCC than in ADC, but the difference didn’t reach statistical significance (p = 0.269). In the subgroup of 8 EGFRv III-positive patients, 7 (87.5%) were male, 6 patients (75.0%) were smokers or former smokers,. No EGFR mutation was detected. In 13 advanced SCC patients who received treatment with EGFR-TKI, no patient harboring EGFRv III was found, and 3 patients (23.08%) were tested for EGFR mutation. Conclusions: The frequency of EGFRv III in Chinese NSCLC was low and squamous histology, smokers or former- smokers, and male gender might be related to EGFRv III and have effects exclusive of EGFR mutation.
ASSOCIATION OF NT-PROBNP, PULSE PRESSURE WITH HEART FAILURE AND CARDIOVASCULAR EVENTS: ATHEROSCLEROSIS RISK IN COMMUNNITIES (ARIC) STUDY
Authors: Aliza Hussain, Wensheng Sun, Anita Deswal, James de Lemos, John Mcevoy, Ron Hoogeveen, Kunihiro Matsushita, David Aguilar, Biykem Bozkurt, Salim S. Virani, Amil M. Shah, Elizabeth Selvin, Chiadi Ndumele, Christie M. Ballantyne, Vijay Nambi
Journal: Journal of the American College of Cardiology (2020)
CLINICAL CHARACTERISTICS AND OUTCOMES OF ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION PATIENTS WITH CARDIOGENIC SHOCK AND CARDIAC ARREST
Authors: Mohamed Omer, Ross Garberich, Scott W. Sharkey, Emmanouil Brilakis, Paul Sorajja, Timothy D. Henry, Mario Gossl, Christian Schmidt, Ivan Chavez, Michael Mooney, M. Nicholas Burke, Michael Megaly, Katarzyna Hryniewicz, Yale Wang, Jay Traverse, Santiago Garcia
Journal: Journal of the American College of Cardiology (2020)
GDC-0449 in patients with advanced chondrosarcomas: A French Sarcoma Group (FSG)/French and U.S. National Cancer Institutes phase II collaborative study.
Authors: Antoine Italiano, Axel Le Cesne, Philippe A Cassier, Isabelle Ray-Coquard, Julien Domont, Sophie Piperno-Neumann, Florence Duffaud, Nicolas Penel, Naoko Takebe, Jean-Yves Blay, Binh Bui Nguyen
Journal: Journal of Clinical Oncology (2012)

10005 Background: Chondrosarcomas (CS) exhibit a strong activation of hedgehog (Hh) signaling which plays a crucial role in cartilage tumorigenesis. Preclinical data show that hedgehog blockade reduces strongly chondrosarcoma cell proliferation and tumour size. GDC-0449 is a small-molecule antagonist of the Hh pathway. Methods: This is a multicentric single-arm phase 2 clinical trial based on two-stage Simon’s design which assesses safety and efficacy of GDC-0449 in patients (pts) with advanced CS. All pts had to have documented progressive disease (PD) as per RECIST 1.1 before study entry. Pts receive GDC-0449 150mg (oral route), daily until PD or unacceptable toxicity. The primary endpoint is the 6-month non-PD rate according to RECIST. Based on the following hypotheses: 20% 6-month non-PD rate (H0), 40% acceptable 6-month non-PD rate (H1), 10% type I error rate, 90% power, a total of 37 assessable pts are necessary (17 for the first stage + 20 for the second stage). Following the inclusion of the first 17 pts, if ≥ four pts are progression-free at 6 months, the accrual will continue. In order to account for not assessable pts (+/- 10%), 41 pts will be recruited. Accrual started in February 2011 in six centers of the FSG. Results: As of January 24 2012, 40 pts (28 males, 12 females) have been included in the study. Median age is 59 years (30-86). The most frequent histological subtype is conventional CS (n=32). Twenty eight pts (70%) had grade 1 or 2 adverse events (AE) possibly related to the drug whereas 3 pts (7.5%) had grade 3 or 4 AE. The planned interim statistical analysis performed after central histological and radiological review showed that four patients out of the first 17 evaluable patients had stable disease indicating that GDC-0449 had reached the primary endpoint to justify continuing accrual after the 1 st step of the study. 15 pts are still on treatment. Molecular analyses are available for 21 pts. No mutation of SMO was detected. qRT-PCR experiments and PTCH sequencing are ongoing. Conclusions: GDC-0449 is well tolerated and shows some activity in a subset of pts with advanced CS. Final clinical and molecular data will be presented at the meeting.
Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients With Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma
Authors: Daniel V.T. Catenacci, Drew Rasco, Jeeyun Lee, Sun Young Rha, Keun-Wook Lee, Yung Jue Bang, Johanna Bendell, Peter Enzinger, Neyssa Marina, Hong Xiang, Wei Deng, Janine Powers, Zev A. Wainberg
Journal: Journal of Clinical Oncology (2020)

PURPOSE To evaluate the safety, pharmacokinetics, and preliminary activity of bemarituzumab in patients with FGFR2b-overexpressing gastric and gastroesophageal junction adenocarcinoma (GEA). PATIENTS AND METHODS FPA144-001 was a phase I, open-label, multicenter trial consisting of the following 3 parts: part 1a involved dose escalation in patients with recurrent solid tumors at doses ranging from 0.3 to 15 mg/kg; part 1b involved dose escalation in patients with advanced-stage GEA; and part 2 involved dose expansion in patients with advanced-stage GEA that overexpressed FGFR2b at various levels (4 cohorts; high, medium, low, and no FGFR2b overexpression) and 1 cohort of patients with FGFR2b-overexpressing advanced-stage bladder cancer. RESULTS Seventy-nine patients were enrolled; 19 were enrolled in part 1a, 8 in part 1b, and 52 in part 2. No dose-limiting toxicities were reported, and the recommended dose was identified as 15 mg/kg every 2 weeks based on safety, tolerability, pharmacokinetic parameters, and clinical activity. The most frequent treatment-related adverse events (TRAEs) were fatigue (17.7%), nausea (11.4%), and dry eye (10.1%). Grade 3 TRAEs included nausea (2 patients) and anemia, neutropenia, increased AST, increased alkaline phosphatase, vomiting, and an infusion reaction (1 patient each). Three (10.7%) of 28 patients assigned to a cohort receiving a dose of ≥ 10 mg/kg every 2 weeks for ≥ 70 days reported reversible grade 2 corneal TRAEs. No TRAEs of grade ≥ 4 were reported. Five (17.9%; 95% CI, 6.1% to 36.9%) of 28 patients with high FGFR2b-overexpressing GEA had a confirmed partial response. CONCLUSION Overall, bemarituzumab seems to be well tolerated and demonstrated single-agent activity as late-line therapy in patients with advanced-stage GEA. Bemarituzumab is currently being evaluated in combination with chemotherapy in a phase III trial as front-line therapy for patients with high FGFR2b-overexpressing advanced-stage GEA.
CANAGLIFLOZIN (CANA) REDUCES CARDIOVASCULAR (CV) AND RENAL EVENTS INDEPENDENT OF BASELINE HEART FAILURE (HF): A CREDENCE SECONDARY ANALYSIS
Authors: Ashish Sarraju, JingWei Li, Christopher P. Cannon, Tara I. Chang, Rajiv Agarwal, George L. Bakris, David M. Charytan, Dick de Zeeuw, Tom Greene, Hiddo J.L. Heerspink, Adeera Levin, Bruce Neal, Carol Pollock, David C. Wheeler, Yshai Yavin, Hong Zhang, Bernard Zinman, Vlado Perkovic, Meg Jardine, Kenneth W. Mahaffey
Journal: Journal of the American College of Cardiology (2020)
APOLIPOPROTEIN B, PCSK9 INHIBITION WITH ALIROCUMAB, AND ISCHEMIC CARDIOVASCULAR EVENTS AFTER ACUTE CORONARY SYNDROME: INSIGHTS FROM THE ODYSSEY OUTCOMES TRIAL
Authors: Emil Hagstrom, Philippe Gabriel Steg, Michael Szarek, Deepak Bhatt, Vera Bittner, Nicolas Danchin, Rafael Diaz, Shaun Goodman, Robert A. Harrington, Johan Wouter Jukema, Yong-Un Kim, Evangelos Liberopoulos, Nikolaus Marx, Jennifer McGinniss, Matthew Roe, Michael Louie, Harvey White, Andreas Zeiher, Gregory G. Schwartz
Journal: Journal of the American College of Cardiology (2020)
RISK OF ARRHYTHMIC EVENTS FOLLOWING ALCOHOL SEPTAL ABLATION FOR HYPERTROPHIC CARDIOMYOPATHY USING CONTINUOUS IMPLANTABLE LOOP RECORDING
Authors: Peter Bleszynski, Ilan Goldenberg, Genaro Fernandez, Erik Howell, Anita Chen, Scott McNitt, Jeffrey Bruckel, Christopher Cove, Mehmet Aktas
Journal: Journal of the American College of Cardiology (2020)
QIM20-119: The Efficacy of Cost-Effective Fixed Dose of Rasburicase Compared to Weight-Based Dose in Treatment and Prevention of Tumor Lysis Syndrome (TLS)
Authors: Ahmad M. Abu-Hashyeh, Mena Shenouda, Mohamed Al-Sharedi
Journal: Journal of the National Comprehensive Cancer Network (2020)

"QIM20-119: The Efficacy of Cost-Effective Fixed Dose of Rasburicase Compared to Weight-Based Dose in Treatment and Prevention of Tumor Lysis Syndrome (TLS)" published on 20 Mar 2020 by National Comprehensive Cancer Network.
POST-TRANSPLANT OUTCOMES FOR PATIENTS BASED ON DURATION OF SMOKING CESSATION AT TIME OF HEART TRANSPLANT (HT) LISTING
Authors: Grace Liu, Eugene Christopher DePasquale, Joseph Rahman, Kruti Pandya, Darko Vucicevic, Aaron Wolfson, Robin Chand, Jonathan Nattiv, Pooya Banankhah, Percy Genyk, Jason Li, Philip Kingsford, Ajay Vaidya
Journal: Journal of the American College of Cardiology (2020)
Horizon Scan of the Belt and Road Initiative
Authors: Alice C. Hughes, Alex M. Lechner, Alexander Chitov, Alexander Horstmann, Amy Hinsley, Angela Tritto, Anthony Chariton, Binbin V. Li, Delfin Ganapin, Eugene Simonov, Katherine Morton, Kemel Toktomushev, Marc Foggin, May Tan-Mullins, Michael C. Orr, Richard Griffiths, Richard Nash, Scott Perkin, Raphaël Glémet, Minsun Kim, Douglas W. Yu
Journal: Trends in Ecology & Evolution (2020)
GENETIC ASSOCIATION OF VANIN 1 GENE POLYMORPHISM WITH MYOCARDIAL INFARCTION
Authors: Muhammad Siddique Pir, Sidra Bokhari, Ummara Bilal, Waqas Ahmad, Najam Saqib, Abdul Mannan Khan Minhas, Muhammad Ajmal, Maleeha Azam, Raheel Qamar
Journal: Journal of the American College of Cardiology (2020)
Outcomes of extra-skeletal versus skeletal Ewing sarcoma patients treated with standard chemotherapy protocol.
Authors: Samer Salah, Fawzi Jamil Abuhijla, Taleb Ismaeel, Sameer Yaser, Iyad Yasin Sultan, Ahmad Shehadeh, Samer Abelal, Abdelatif Al-Mousa, Ramiz Abuhijlih
Journal: Journal of Clinical Oncology (2019)

11027 Background: Extra-skeletal ewing sarcomas (ES) are rare, and data on outcomes following standard ES chemotherapy protocols are very limited. Methods: We retrospectively collected data on skeletal and extra-skeletal ES patients who presented with localized disease from January, 2006 to June, 2018. Disease and treatment characteristics were compared between the two groups by the chi-square test. Overall survival (OS) and local recurrence free survival (LRFS) were estimated by the Kaplan-Meier method and compared by the Log-rank test. Results: A total of 120 patients were included. Twenty-nine (24%) had extra-skeletal and 91 (76%) had skeletal ES. Location was in the extremity in 51 (43%) and non-extremity in 69 (57%). For extra-skeletal ES, tumors originated from soft tissue in 23 (79%), and viscera in 6 (21%). All patients received standard vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE), with a plan for local control at week 12 of the protocol. Local control was by surgery in 76 (63%) and radiotherapy in 44 (37%). At a median follow up of 38 months, there was no difference in 5-year OS between extra-skeletal and skeletal ES patients (67% and 70% respectively, p = 0.96). Patients with visceral ES had inferior 5-year OS compared to all others (soft-tissue extra-skeletal and skeletal ES); 33% vs. 72%; p = 0.013. Resectability rate was not different between extra-skeletal and skeletal ES patients (54% and 69% respectively, p= 0.11). Furthermore, among patients who underwent surgery, there was no difference between extra-skeletal and skeletal ES patients in R0 resection rate (86% and 89% respectively, p= 0.52) and poor ( &lt; 90%) tumor necrosis rate (62% and 46% respectively, p= 0.31). However, more local recurrences (28% vs. 10%, p= 0.034) and inferior 5-year LRFS (74% vs. 83%; p = 0.042) were observed in the extra-skeletal group, although more extra-skeletal patients received adjuvant radiotherapy; 11 (73%) vs. 21 (36%), p = 0.01. Conclusions: Patients with localized extra-skeletal ES have OS outcomes that are comparable to skeletal ES treated with standard VDC-IE chemotherapy. However, extra-skeletal ES patients are at significantly higher risk of local recurrence.