tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of Drug-Eluting Stents Optimized for Biocompatibility vs Bare-Metal Stents With a Single Month of Dual Antiplatelet Therapy
Authors: Rahman Shah, Sunil V. Rao, Samuel B. Latham, David E. Kandzari
Journal: JAMA Cardiology (2018)

A significant number of patients receive bare-metal stents (BMSs) instead of drug-eluting stents (DESs) to shorten the duration of dual antiplatelet therapy (DAPT). Emerging evidence suggests that new-generation DESs, particularly those optimized for biocompatibility, may be more efficacious and safer than BMSs, even with a single month of DAPT after stent implantation.To evaluate the efficacy and safety of DESs compared with BMSs for coronary intervention with a single month of DAPT.Human studies found in PubMed, the Cochrane databases through April 2018, and reference lists of selected articles.Randomized clinical trials were included if they enrolled patients undergoing percutaneous coronary intervention and randomly assigned each patient to treatment with either DESs or BMSs. The additional inclusion criterion was use of only 1 month of DAPT poststent implantation.Two reviewers independently extracted the data. Odds ratios (ORs) were calculated using random-effects models.The efficacy end points were major adverse cardiac events, myocardial infarction, target vessel revascularization, ischemia-driven target lesion revascularization, cardiac mortality, and all-cause mortality at 1 year. The safety outcomes were stent thrombosis and bleeding complications.Data from 3 randomized clinical trials involving 3943 patients were included (2457 men [62.3%]; mean [SD] age ranging from 75.7 [9.3] years to 81.4 [4.3] years per trial subgroup). Coronary intervention with DESs reduced the rates for major adverse cardiac events (OR, 0.68 [95% CI, 0.57-0.82]; P < .001), target lesion revascularization (OR, 0.38 [95% CI, 0.22-0.67]; P = .001), target vessel revascularization (OR, 0.50 [95% CI, 0.38-0.65]; P < .001), and myocardial infarction (OR, 0.51 [95% CI, 0.31-0.83]; P = .01) compared with BMSs at 1 year. The incidence of stent thrombosis was also lower with DESs compared with BMSs (1.8% vs 2.8%), but this difference was not statistically significant in the random-effects model. Additionally, the 2 stent types did not differ in the risks of all-cause mortality, cardiac mortality, and bleeding.In the limited number of randomized clinical trials comparing DESs with BMSs with shortened DAPT durations in patients who have high bleeding risk or are uncertain candidates for prolonged DAPT, coronary intervention with specific DESs optimized for biocompatibility is not only safe but also efficacious, even with only 1 month of DAPT.
Antisense oligonucleotides targeting mutant Ataxin-7 restore visual function in a mouse model of spinocerebellar ataxia type 7
Authors: Chenchen Niu, Thazah P. Prakash, Aneeza Kim, John L. Quach, Laryssa A. Huryn, Yuechen Yang, Edith Lopez, Ali Jazayeri, Gene Hung, Bryce L. Sopher, Brian P. Brooks, Eric E. Swayze, C. Frank Bennett, Albert R. La Spada
Journal: Science Translational Medicine (2018)

Intravitreal injection of antisense oligonucleotides targeting mutated Ataxin-7 improves visual function in a mouse model of spinocerebellar ataxia type 7.
Postpartum Care in the United States — New Policies for a New Paradigm
Authors: Mara E. Murray Horwitz, Rose L. Molina, Jonathan M. Snowden
Journal: New England Journal of Medicine (2018)

Interview with Dr. Susan Mann on steps that hospitals can take to keep women safe during and after childbirth. (08:46)Download New recommendations from the American College of Obstetricians and Gynecologists could support a much-needed shift toward improved postpartum care in the United States. But current insurance-reimbursement and parental leave policies may limit their impact.
Loss of the GPI-anchor in B-lymphoblastic leukemia by epigenetic downregulation of<i>PIGH</i>expression
Authors: Floris C. Loeff, Kevin Rijs, Esther H. M. van Egmond, Willem H. Zoutman, Xiaohang Qiao, Wilhelmina G. M. Kroes, Sabrina A. J. Veld, Marieke Griffioen, Maarten H. Vermeer, Jacques Neefjes, J. H. Frederik Falkenburg, Constantijn J. M. Halkes, Inge Jedema
Journal: American Journal of Hematology (2018)

Abstract Adult B‐lymphoblastic leukemia (B‐ALL) is a hematological malignancy characterized by genetic heterogeneity. Despite successful remission induction with classical chemotherapeutics and novel targeted agents, enduring remission is often hampered by disease relapse due to outgrowth of a pre‐existing subclone resistant against the treatment. In this study, we show that small glycophosphatidylinositol (GPI)‐anchor deficient CD52‐negative B‐cell populations are frequently present already at diagnosis in B‐ALL patients, but not in patients suffering from other B‐cell malignancies. We demonstrate that the GPI‐anchor negative phenotype results from loss of mRNA expression of the PIGH gene, which is involved in the first step of GPI‐anchor synthesis. Loss of PIGH mRNA expression within these B‐ALL cells follows epigenetic silencing rather than gene mutation or deletion. The coinciding loss of CD52 membrane expression may contribute to the development of resistance to alemtuzumab (ALM) treatment in B‐ALL patients resulting in the outgrowth of CD52‐negative escape variants. Additional treatment with 5‐aza‐2′‐deoxycytidine may restore expression of CD52 and revert ALM resistance.
Simultaneous 18F-FDG PET/MRI Assists Diagnosis of a Rare Disease, MELAS
Authors: Fang Liu, Weiwei Ruan, Yichun Wang, Xiaoli Lan
Journal: Clinical Nuclear Medicine (2018)

Abstract MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a rare congenital mitochondrial DNA mutation disease. Here, we report a 4-year-old girl, who presented with short stature, mental retardation, and recurrent seizures, underwent simultaneous 18 F-FDG PET/MRI examination. An interesting contradiction images were found on bilateral frontal, left temporal, occipital, and parietal lobes, which were with high blood flow shown on 3D-ASL perfusion images, but low uptake of 18 F-FDG on PET images. The contradiction of high blood flow and low glucose metabolism gave us a clue to make the diagnosis of MELAS. The final diagnosis was MELAS confirmed by genetic testing.
Evaluation of Bisphenol A (BPA) Exposures on Prostate Stem Cell Homeostasis and Prostate Cancer Risk in the NCTR-Sprague-Dawley Rat: An NIEHS/FDA CLARITY-BPA Consortium Study
Authors: Gail S. Prins, Wen-Yang Hu, Lishi Xie, Guang-Bin Shi, Dan-Ping Hu, Lynn Birch, Maarten C. Bosland
Journal: Environmental Health Perspectives (2018)

Background: Previous work determined that early life exposure to low-dose Bisphenol A (BPA) increased rat prostate cancer risk with aging. Herein, we report on prostate-specific results from CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity), which aims to resolve uncertainties regarding BPA toxicity. Objectives: We sought to a) reassess whether a range of BPA exposures drives prostate pathology and/or alters prostatic susceptibility to hormonal carcinogenesis, and b) test whether chronic low-dose BPA targets prostate epithelial stem and progenitor cells. Methods: Sprague-Dawley rats were gavaged daily with vehicle, ethinyl estradiol (EE) or 2.5–25,000μg BPA/kg-BW during development or chronically, and prostate pathology was assessed at one year. One developmentally exposed cohort was given testosterone plus estradiol (T+E) implants at day 90 to promote carcinogenesis with aging. Epithelial stem and progenitor cells were isolated by prostasphere (PS) culture from dorsolateral prostates (DLP) of rats continuously exposed for six months to 2.5–250μg BPA/kg-BW. Gene expression was analyzed by quantitative real time reverse transcription polymerase chain reaction (qRT-PCR). Results: Exposure to BPA alone at any dose did not drive prostate pathology. However, rats treated with EE, 2.5, 250, or 25,000μg BPA/kg-BW plus T+E showed greater severity of lateral prostate intraepithelial neoplasia (PIN), and DLP ductal adenocarcinoma multiplicity was markedly elevated in tumor-bearing rats exposed to 2.5μg BPA/kg-BW. DLP stem cells, assessed by PS number, doubled with chronic EE and 2.5μg BPA/kg-BW exposures. PS size, reflecting progenitor cell proliferation, was greater at 25 and 250μg BPA doses, which also shifted lineage commitment toward basal progenitors while reducing luminal progenitor cells. Conclusions: Together, these results confirm and extend previous evidence using a rat model and human prostate epithelial cells that low-dose BPA augments prostate cancer susceptibility and alters adult prostate stem cell homeostasis. Therefore, we propose that BPA exposures may contribute to the increased carcinogenic risk in humans that occurs with aging. https://doi.org/10.1289/EHP3953
Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer
Authors: Alicia Latham, Preethi Srinivasan, Yelena Kemel, Jinru Shia, Chaitanya Bandlamudi, Diana Mandelker, Sumit Middha, Jaclyn Hechtman, Ahmet Zehir, Marianne Dubard-Gault, Christina Tran, Carolyn Stewart, Margaret Sheehan, Alexander Penson, Deborah DeLair, Rona Yaeger, Joseph Vijai, Semanti Mukherjee, Jesse Galle, Mark A. Dickson, Yelena Janjigian, Eileen M. O’Reilly, Neil Segal, Leonard B. Saltz, Diane Reidy-Lagunes, Anna M. Varghese, Dean Bajorin, Maria I. Carlo, Karen Cadoo, Michael F. Walsh, Martin Weiser, Julio Garcia Aguilar, David S. Klimstra, Luis A. Diaz, Jose Baselga, Liying Zhang, Marc Ladanyi, David M. Hyman, David B. Solit, Mark E. Robson, Barry S. Taylor, Kenneth Offit, Michael F. Berger, Zsofia K. Stadler
Journal: Journal of Clinical Oncology (2018)

Microsatellite instability (MSI) and/or mismatch repair deficiency (MMR-D) testing has traditionally been performed in patients with colorectal (CRC) and endometrial cancer (EC) to screen for Lynch syndrome (LS)-associated cancer predisposition. The recent success of immunotherapy in high-frequency MSI (MSI-H) and/or MMR-D tumors now supports testing for MSI in all advanced solid tumors. The extent to which LS accounts for MSI-H across heterogeneous tumor types is unknown. Here, we establish the prevalence of LS across solid tumors according to MSI status.MSI status was determined using targeted next-generation sequencing, with tumors classified as MSI-H, MSI-indeterminate, or microsatellite-stable. Matched germline DNA was analyzed for mutations in LS-associated mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, EPCAM). In patients with LS with MSI-H/I tumors, immunohistochemical staining for MMR-D was assessed.Among 15,045 unique patients (more than 50 cancer types), LS was identified in 16.3% (53 of 326), 1.9% (13 of 699), and 0.3% (37 of 14,020) of patients with MSI-H, MSI-indeterminate, and microsatellite-stable tumors, respectively ( P < .001). Among patients with LS with MSI-H/I tumors, 50% (33 of 66) had tumors other than CRC/EC, including urothelial, prostate, pancreas, adrenocortical, small bowel, sarcoma, mesothelioma, melanoma, gastric, and germ cell tumors. In these patients with non-CRC/EC tumors, 45% (15 of 33) did not meet LS genetic testing criteria on the basis of personal/family history. Immunohistochemical staining of LS-positive MSI-H/I tumors demonstrated MMR-D in 98.2% (56 of 57) of available cases.MSI-H/MMR-D is predictive of LS across a much broader tumor spectrum than currently appreciated. Given implications for cancer surveillance and prevention measures in affected families, these data support germline genetic assessment for LS for patients with an MSI-H/MMR-D tumor, regardless of cancer type or family cancer history.
Cardiovascular screening in Olympic athletes: time to achieve a uniform standard
Authors: Antonio Pelliccia, Jonathan A Drezner
Journal: British Journal of Sports Medicine (2018)

In British Journal of Sports Medicine , Toresdahl  et al  describe the preparticipation cardiovascular (CV) screening practices implemented for athletes participating in the 2016 Rio Olympic Games.1 This study is of particular importance because it highlights the range of CV screening in the world’s most elite athletes.

The chief medical officers (CMOs) present in Rio completed an online survey about the CV screening conducted in their countries for athletes selected to participate in the 2016 Olympic Games. Over 80% of the CMOs replied to the survey, providing a reliable picture of current CV screening practices in Olympic athletes. Most countries (70%) perform annual CV screening, with 85% implementing a personal and family history and 75% also using a screening ECG. Expense and lack of a cardiology consultant were cited as the most common reasons not to include ECG.

The issue of preparticipation CV screening with or without ECG has been vigorously debated within the scientific community since 2006 when Corrado et al 2 demonstrated a substantial decrease in sudden cardiac death (SCD) in Italian athletes following implementation of an ECG-based national screening programme. The Italian experience has generated considerable criticism over time, with numerous papers supporting or …
Abstract 15575: Can Rhythm Control by Catheter Ablation Improve Exercise Capacity in Asymptomatic Patients With Chronic Atrial Fibrillation?
Authors: Jong-Ho Nam, Chan-Hee Lee, Kyu-Hwan Park, Jang-Won Son, Ung Kim, Jong-Seon Park, Dong-Gu Shin, Young-Jo Kim
Journal: Circulation (2015)

Introduction: Radiofrequency catheter ablation (RFCA) for asymptomatic atrial fibrillation (AF) is not indicated due to limited data on it’s clinical efficacy. This study evaluated the change in oxygen kinetics and cardiopulmonary performance parameters after RFCA for asymptomatic (Canadian Cardiovascular Society-Severity of AF scores = 0) Chronic AF patients. Methods: A total of 57 patients with asymptomatic chronic AF (age 60 ± 9 year-old, 89.5% male, AF duration 51 ± 49 months) divided into 2 groups according to sinus rhythm conversion via RFCA: Group 1 (Rate control, n=32); Group 2 (Rhythm control, n=25). The patients who achieved sinus rhythm by antiarrhythmics (n=20) and cardioversion (n=4) were excluded. All underwent two times of treadmill cardiopulmonary exercise tests (modified Bruce protocol, Quark CPET®, COSMED, Italy) before and after each treatment (follow-up periods, 250 ± 181 days). Peak oxygen uptake (Peak VO2, ml/min/Kg) as aerobic capacity, O2-pulse at peak (ml/beat) for cardiovascular response, and the slope of the increase in ventilation to the increase in CO2 output (VE-VCO2 slope) for gas exchange were compared. Results: The Group 1 patients were older (62 ± 7 vs. 57 ± 10 year-old) and had longer duration of AF (63 ± 52 vs. 36 ± 39 months) than the Group 2 patients. The O2-pulse at peak were much increased in Group 2 during follow-up periods (Group 1, from 10.0 ± 3.1 to 10.6 ± 3.1, P=0.137; Group 2, 12.1 ± 3.8 to 15.4 ± 3.8, P=0.003). During exercise, maximal exercise heart rate was significantly lower in Group 2 after treatment (Group 1, 162±25 vs. Group 2, 128±29 bpm, P&lt;0.001). However, the value of Peak VO2 and VE-VCO2 slope were not different between before and after treatment, and between 2 groups. Conclusion: The results from the present study indicate that improvement of maximal aerobic capacity and exercise tolerance are negligible in asymptomatic patients with chronic AF following successful catheter ablation.
Predicting Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer
Authors: Hyunjong Lee, Dong-eun Lee, Sohyun Park, Tae Sung Kim, So-Youn Jung, Seeyoun Lee, Han Sung Kang, Eun Sook Lee, Sung Hoon Sim, In Hae Park, Keun Seok Lee, Young Mi Kwon, Sun Young Kong, Jungnam Joo, Hae Jeong Jeong, Seok-ki Kim
Journal: Clinical Nuclear Medicine (2018)

Purpose The aim of this study was to develop a combined statistical model using both clinicopathological factors and texture parameters from 18 F-FDG PET/CT to predict responses to neoadjuvant chemotherapy in patients with breast cancer. Materials and Methods A total of 435 patients with breast cancer were retrospectively enrolled. Clinical and pathological data were obtained from electronic medical records. Texture parameters were extracted from pretreatment FDG PET/CT images. The end point was pathological complete response, defined as the absence of residual disease or the presence of residual ductal carcinoma in situ without residual lymph node metastasis. Multivariable logistic regression modeling was performed using clinicopathological factors and texture parameters as covariates. Results In the multivariable logistic regression model, various factors and parameters, including HER2, histological grade or Ki-67, gradient skewness, gradient kurtosis, contrast, difference variance, angular second moment, and inverse difference moment, were selected as significant prognostic variables. The predictive power of the multivariable logistic regression model incorporating both clinicopathological factors and texture parameters was significantly higher than that of a model with only clinicopathological factors ( P = 0.0067). In subgroup analysis, texture parameters, including gradient skewness and gradient kurtosis, were selected as independent prognostic factors in the HER2-negative group. Conclusions A combined statistical model was successfully generated using both clinicopathological factors and texture parameters to predict the response to neoadjuvant chemotherapy. Results suggest that addition of texture parameters from FDG PET/CT can provide more information regarding treatment response prediction compared with clinicopathological factors alone.
LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating P21 signaling
Authors: Liangsong Zhu, Jianfeng Wang, Wen Kong, Jiwei Huang, Baijun Dong, Yiran Huang, Wei Xue, Jin Zhang
Journal: Acta Pharmaceutica Sinica B (2018)

Histone lysine-specific demethylase 1 (LSD1) has been implicated in the disease progression of several types of solid tumors. This study provides the first evidence showing that LSD1 overexpression occurred in 62.6% (224/358) of clear cell renal cell carcinomas (ccRCC). LSD1 expression was associated with the progression of ccRCC, as indicated by TNM stage (P=0.006), especially tumor stage (P=0.017) and lymph node metastasis (P=0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival (P<0.001) and recurrence-free survival (P<0.001) of ccRCC patients. We further show that LSD1 inhibition by siRNA knockdown or using the small molecule inhibitor SP2509 suppressed the growth of ccRCC in vitro and in vivo. Mechanistically, inhibition of LSD1 decreased the H3K4 demethylation at the CDKN1A gene promoter, which was associated with P21 upregulation and cell cycle arrest at G1/S in ccRCC cells. Our findings provide new mechanistic insights into the role of LSD1 in ccRCC and suggest the therapeutic potential of LSD1 inhibitors in ccRCC treatment.
First-in-Human CLL1-CD33 Compound CAR T Cell Therapy Induces Complete Remission in Patients with Refractory Acute Myeloid Leukemia: Update on Phase 1 Clinical Trial
Authors: Fang Liu, Yuanzhen Cao, Kevin Pinz, Yu Ma, Masayuki Wada, Kevin Chen, Gina Ma, Jiaqi Shen, Charlotte Olivia Tse, Yi Su, Yisong Xiong, Guangcui He, Yecheng Li, Yupo Ma
Journal: Blood (2018)
Lung Ultrasound for Critically Ill Patients
Authors: Francesco Mojoli, Bélaid Bouhemad, Silvia Mongodi, Daniel Lichtenstein
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Section:ChooseTop of pageAbstract <<The Technique and Basic S...A Diagnostic Tool for the...A Monitoring Tool: Lung A...Lung Ultrasound–guided Me...Detection and Management ...Limitations of Lung Ultra...Future Perspectives for L...ConclusionsReferencesCITING ARTICLES
Discovery of New Fusion Transcripts in a Cohort of Pediatric Solid Cancers at Relapse and Relevance for Personalized Medicine
Authors: Célia Dupain, Anne C. Harttrampf, Yannick Boursin, Manuel Lebeurrier, Windy Rondof, Guillaume Robert-Siegwald, Pierre Khoueiry, Birgit Geoerger, Liliane Massaad-Massade
Journal: Molecular Therapy (2018)

We hypothetized that pediatric cancers would more likely harbor fusion transcripts. To dissect the complexity of the fusions landscape in recurrent solid pediatric cancers, we conducted a study on 48 patients with different relapsing or resistant malignancies. By analyzing RNA sequencing data with a new in-house pipeline for fusions detection named ChimComp, followed by verification by real-time PCR, we identified and classified the most confident fusion transcripts (FTs) according to their potential biological function and druggability. The majority of FTs were predicted to affect key cancer pathways and described to be involved in oncogenesis. Contrary to previous descriptions, we found no significant correlation between the number of fusions and mutations, emphasizing the particularity to study pre-treated pediatric patients. A considerable proportion of FTs containing tumor suppressor genes was detected, reflecting their importance in pediatric cancers. FTs containing non-receptor tyrosine kinases occurred at low incidence and predominantly in brain tumors. Remarkably, more than 30% of patients presented a potentially druggable high-confidence fusion. In conclusion, we detected new oncogenic FTs in relapsing pediatric cancer patients by establishing a robust pipeline that can be applied to other malignancies, to detect and prioritize experimental validation studies leading to the development of new therapeutic options.
Short interpregnancy interval is associated with increased risks to the mother and fetus
Authors: Jacqui Wise
Journal: BMJ (2018)

A gap of less than a year between giving birth and conceiving another child is associated with increased risks for women of all ages, according to a large cohort study.1

A short interpregnancy interval was associated with risks to the fetus and infant, although to a greater extent for younger women (aged 20 to 34 years) than for women 35 years or older. For older women, an interpregnancy interval under 12 months was associated with a significant increased risk of maternal death or severe morbidity …
Atezolizumab in Combination with Daratumumab with or without Lenalidomide or Pomalidomide: A Phase Ib Study in Patients with Multiple Myeloma
Authors: Hearn Jay Cho, Luciano J Costa, Faith E. Davies, Natalia Neparidze, Ravi Vij, Yuning Feng, Anastasia Teterina, Elisabeth Wassner Fritsch, Michael Wenger, Jonathan L Kaufman
Journal: Blood (2018)
Paraneoplastic hyperleucocytosis in a melanoma patient after initiation of ipilimumab and nivolumab combination therapy
Authors: Thilo Gambichler, E. Stockfleth, L. Susok
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Paraneoplastic hyperleucocytosis (PH) is sporadically seen in patients with advanced solid tumors. <h3>Case presentation</h3> We report a female patient with disseminated melanoma metastases. Two days after the first dosage of combined immunotherapy using the cytotoxic T lymphocyte antigen-4 (CTLA-4) blocker ipilimumab and the programmed death receptor-1 (PD-1) blocker nivolumab the patient developed asymptomatic hyperleucocytosis (over 120.000 leucocytes per μl) associated with elevated granulocyte colony-stimulating factor blood levels. Hematological and infectious disorders could be ruled out. Although paraneoplastic hyperleucocytosis spontaneously resolved she died from progressive disease about 60&nbsp;days after start of treatment. <h3>Conclusions</h3> PH is extremely rare in malignant melanoma, however, most patients who developed this complication had preceding immunotherapies such as interleukin-2. The latter observation and the fact that our patient developed PH rapidly after initiation of ipilimumab and nivolumab immunotherapy indicate an immune-mediated mechanism which may trigger PH under unknown circumstances. The development of paraneoplastic hyperleucocytosis indicates a very poor prognosis.