tbuckley/cabot-search huggingface dataset:
Letter by Jogia and Liang Regarding Article, “Evaluating the Atrial Myopathy Underlying Atrial Fibrillation: Identifying the Arrhythmogenic and Thrombogenic Substrate”
Authors: Dilesh Jogia, Michael Liang
Journal: Circulation (2016)

Goldberger et al. 1 The authors discussed potential substrates for the development of atrial fibrillation (AF), however, we were surprised that they did not emphasize the crucial role that hypertension plays in the development of AF.A report published more than 10 years ago found that hypertension was the leading cause of death and disease in the world. 2 Arterial hypertension is found in 65% to 70% of patients with AF but in only 40% of the population, and it is the most common comorbidity found in AF registries in Germany and Europe. [3]][5] Although these statistics suggest a causal link between hypertension and AF, the mechanism by which it predisposes to AF is not well understood and requires more research.The strong association between hypertension and AF behooves us to redouble our collective efforts to identify and treat hypertension in an attempt to reduce the burden of this disease, which will no doubt favorably affect the ever-increasing prevalence of AF in most communities.The role of hypertension should not be understated in any contemporary review relating possible substrates for this condition.
Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study
Authors: Barbara B Warner, Elena Deych, Yanjiao Zhou, Carla Hall-Moore, George M Weinstock, Erica Sodergren, Nurmohammad Shaikh, Julie A Hoffmann, Laura A Linneman, Aaron Hamvas, Geetika Khanna, Lucina C Rouggly-Nickless, I Malick Ndao, Berkley A Shands, Marilyn Escobedo, Janice E Sullivan, Paula G Radmacher, William D Shannon, Phillip I Tarr
Journal: The Lancet (2016)
Central nervous system involvement by multiple myeloma: A multi‐institutional retrospective study of 172 patients in daily clinical practice
Authors: Artur Jurczyszyn, Norbert Grzasko, Alessandro Gozzetti, Jacek Czepiel, Alfonso Cerase, Vania Hungria, Edvan Crusoe, Ana Luiza Miranda Silva Dias, Ravi Vij, Mark A. Fiala, Jo Caers, Leo Rasche, Ajay K. Nooka, Sagar Lonial, David H. Vesole, Sandhya Philip, Shane Gangatharan, Agnieszka Druzd‐Sitek, Jan Walewski, Alessandro Corso, Federica Cocito, Marie‐Christine M. Vekemans, Erden Atilla, Meral Beksac, Xavier Leleu, Julio Davila, Ashraf Badros, Ekta Aneja, Niels Abildgaard, Efstathios Kastritis, Dorotea Fantl, Natalia Schutz, Tomas Pika, Aleksandra Butrym, Magdalena Olszewska‐Szopa, Lidia Usnarska‐Zubkiewicz, Saad Z. Usmani, Hareth Nahi, Chor S Chim, Chaim Shustik, Krzysztof Madry, Suzanne Lentzsch, Alina Swiderska, Grzegorz Helbig, Renata Guzicka‐Kazimierczak, Nikoletta Lendvai, Anders Waage, Kristian T. Andersen, Hirokazu Murakami, Sonja Zweegman, Jorge J. Castillo
Journal: American Journal of Hematology (2016)

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty‐eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow‐up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively ( P &lt; 0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and &gt;1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively ( P &lt; 0.001). Neurological manifestations, not considered chemotherapy‐related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. Am. J. Hematol. 91:575–580, 2016. © 2016 Wiley Periodicals, Inc.
Vitamin D Status During Pregnancy and Risk of Multiple Sclerosis in Offspring of Women in the Finnish Maternity Cohort
Authors: Kassandra L. Munger, Julia Åivo, Kira Hongell, Merja Soilu-Hänninen, Heljä-Marja Surcel, Alberto Ascherio
Journal: JAMA Neurology (2016)

Vitamin D has been associated with a decreased risk of multiple sclerosis (MS) in adulthood; however, some, but not all, previous studies have suggested that in utero vitamin D exposure may be a risk factor for MS later in life.To examine whether serum 25-hydroxyvitamin D (25[OH]D) levels in early pregnancy are associated with risk of MS in offspring.Prospective, nested case-control study in the Finnish Maternity Cohort conducted in May 2011. We identified 193 individuals with a diagnosis of MS before December 31, 2009, whose mothers are in the Finnish Maternity Cohort and had an available serum sample from the pregnancy with the affected child. We matched 176 cases with 326 controls on region of birth in Finland, date of maternal serum sample collection, date of mother's birth, and date of child's birth.Maternal serum 25(OH)D levels were measured using a chemiluminescence assay. The risk of MS among offspring and association with maternal 25(OH)D levels were the main outcomes. Conditional logistic regression was used and further adjusted for sex of the child, gestational age at the time of sample collection, and season of sample collection to estimate the relative risks and 95% CIs.Of the 193 cases in the study, 163 were female. Of the 331 controls in the study, 218 were female. Seventy percent of serum samples were collected during the first trimester of pregnancy. The mean (SD) maternal vitamin D levels were in the insufficient vitamin D range, but higher in maternal control than case samples (15.02 [6.41] ng/mL vs 13.86 [5.49] ng/mL [to convert to nanomoles per liter, multiply by 2.496]). Maternal vitamin D deficiency (25[OH]D levels <12.02 ng/mL) during early pregnancy was associated with a nearly 2-fold increased risk of MS in the offspring (relative risk, 1.90; 95% CI, 1.20-3.01; P = .006) compared with women who did not have deficient 25(OH)D levels. There was no statistically significant association between the risk of MS and increasing serum 25(OH)D levels (P = .12).Insufficient maternal 25(OH)D during pregnancy may increase the risk of MS in offspring.
Myotomie œsophagienne par voie endoscopique (POEM) répétée: une alternative en cas de symptômes persistants ou récidivants
Journal: Endoscopy (2016)

La myotomie oesophagienne par voie endoscopique, ou POEM, est une technique récente mise au point pour le traitement de l’achalasie du sphincter inférieur de l’œsophage (SIO). Les résultats publiés dans la littérature concernant la faisabilité et la tolérance sont très encourageants. Cette technique pourrait donc être une alternative efficace au traitement chirurgical ou à la dilatation pneumatique endoscopique.
Maurice Anthony Cowan
Authors: Celia Moss, Elizabeth Margaret Cowan
Journal: BMJ (2015)

Maurice Anthony Cowan (“Tony”) was born in Sheffield, attended High Storrs Grammar School, and studied medicine at Sheffield University. He was awarded the Bronze medal and Kaye prize as a second year undergraduate, and the Begley prize in the MRCS(Eng).

His interest in dermatology developed during national service in the Royal Army Medical Corps, where …
Sudden Cardiac Death in the Young
Authors: Michael Ackerman, Dianne L. Atkins, John K. Triedman
Journal: Circulation (2016)

Although the occurrence of sudden cardiac death (SCD) in a young person is a rare event, it is traumatic and often widely publicized. In recent years, SCD in this population has been increasingly seen as a public health and safety issue. This review presents current knowledge relevant to the epidemiology of SCD and to strategies for prevention, resuscitation, and identification of those at greatest risk. Areas of active research and controversy include the development of best practices in screening, risk stratification approaches and postmortem evaluation, and identification of modifiable barriers to providing better outcomes after resuscitation of young SCD patients. Institution of a national registry of SCD in the young will provide data that will help to answer these questions.
Abstract 13388: Accelerated Senescence of Cord Blood Endothelial Progenitor Cells From Premature Neonates is Driven by Sirt1 Decreased Expression
Authors: Paula Frizera Vassallo, Stephanie Simoncini, Isabelle Ligi, Florence Sabatier, Richard Bachelier, Stephane Robert, Julia Morere, Edwige Tellier, Maxime Marcelli, Alain Pascal, Umberto Simeoni, Frederique Magdinier, Francoise Dignat-George, Francine Anfosso
Journal: Circulation (2013)

Epidemiological and experimental studies indicate that low birth weight, in particular preterm birth, is considered a major independent risk factor for cardiovascular diseases. Early vascular dysfu...
BRAF Inhibition in<i>BRAF</i><sup>V600E</sup>-Positive Anaplastic Thyroid Carcinoma
Authors: Annette M. Lim, Graham R. Taylor, Andrew Fellowes, Laird Cameron, Belinda Lee, Rodney J. Hicks, Grant A. McArthur, Christopher Angel, Benjamin Solomon, Danny Rischin
Journal: Journal of the National Comprehensive Cancer Network (2016)

The efficacy of targeted monotherapy for BRAFV600E-positive anaplastic thyroid carcinomas (ATC) is not established. We report 2 cases of BRAFV600E-positive ATC treated with a BRAF inhibitor. A 49-year-old woman with a T4bN1bM0 ATC manifested symptomatic metastatic disease 8 weeks after radical chemoradiotherapy. Within 1 month of BRAF inhibitor monotherapy, a complete symptomatic response was observed, with FDG-PET scan confirming metabolic and radiologic response. Treatment was terminated after 3 months because of disease progression. The patient died 11 months after primary diagnosis. A 67-year-old man received first-line BRAF inhibitor for a T4aN1bM0 ATC. Within 10 days of treatment his pain had stabilized and his tumor had clinically halved in size. Stable disease was achieved for 11 weeks but the patient died 11 months after diagnosis because of disease progression. BRAF inhibitor monotherapy in ATC may obtain clinical benefit of short duration. Upfront combination therapy should be investigated in this patient subgroup.
Clinical trial accrual rates in prostate cancer: Prospective experience from a single institution
Authors: N. J. Vogelzang, B. Wong, D. Pomerantz, K. L. Power, C. W. Adams, R. B. McBeath, A. Dincer, J. T. Symanowski, S. Sharma
Journal: Journal of Clinical Oncology (2007)

15611 Background: Clinical trial (CT) participation is a key to better cancer therapy. The Nevada Cancer Institute (NVCI), the official cancer center of NV, is committed to CT participation. We hypothesized that CT accrual at the NVCI should exceed the national average of 3–5%. Methods: Patient (pt) visits began in 3/05 and by 12/31/07 1363 pts had been seen. Prostate cancer (PC) was the largest group (N=270; 50 with 1 visit only). All records are electronic and entered into a cancer registry. A relatively robust portfolio of PC CTs has been available, thus the cancer registry data base was compared to the CT data base for the 16 PC CTs (8 phase III, 1 phase II, 7 phase I) that accrued pts. The data base records all accruals, screen failures, consent withdrawals, and subsequent treatments (on or off CT). Results: 101 consents were signed by 68 PC pts (25 consented to 2 or more CTs). 31 consents lead to screen failures/consent withdrawal (5 pts were screen failures for 2 CTs while 1 pt was a screen failure for 3 CTs). Screen failure was less common in phase II/III CTs (18/74 =24%) than in phase I CTs (10/27=37%). Most of the phase I screen failures were due to rapid decreases in performance status or organ function dysfunction. Among the 68 unique pts who consented, 35 pts were treated on 1 CT and 16 pts were treated on 2 or more CTs resulting in a total of 51 PC pts being treated on at least 1 CT. Conclusions: CT accrual at the NVCI of PC pts (51/270=19%) exceeds the national average. Reports of CT activity should specify the denominator and include both consent and accrual rates. Screen failure/consent withdrawal was common in this older male population with advanced disease. This analysis has limitations; Phase I CTs were activated only after 10/05, only 1 phase II CT was open during this period and CTs for radiation and surgery alone for PC pts were not open. Thus, the percent of pts on CT should rise as more CTs are activated. No significant financial relationships to disclose.
Molecular selection for colorectal cancer (CRC) patients receiving cetuximab: Final results of a prospective study.
Authors: Mario Scartozzi, Riccardo Giampieri, Michela Del Prete, Alessandra Mandolesi, Luca Faloppi, Khaled Mahmoud Abouelkhair, Maristella Bianconi, Cristian Loretelli, Alessandro Bittoni, Ezzeldin M. Ibrahim, Marina Scarpelli, Rodolfo Montironi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2015)

596 Background: Many markers for a “beyond-RAS” selection of CRC patients receiving cetuximab have been suggested, but none entered clinical practice mainly because prospective validation was lacking. Aim of our study was to evaluate if a molecular profile prospectively analysed was able to predict patients’ clinical outcome more accurately than RAS status alone. Methods: K-RAS (exons 2, 3, 4) wild-type CRC patients, candidates to second/third-line cetuximab with chemotherapy were prospectively allocated, after informed consent, into 2 groups on the basis of their molecular profile: favourable (BRAF and PIK3CA exon 20 wild type, EGFR GCN &gt;2.6, HER-3 Rajkumar score &lt;8, IGF-1 immunostaining &lt;2) and unfavourable (any of the previous markers altered or mutated). After the introduction of N-RAS status (exons 2, 3, 4) only RAS wild type patients were considered eligible for the study. Primary aim was response rate (RR). To detect a difference in terms of RR among patients with an unfavourable profile (estimated around 25%) and patients with a favourable profile (estimated around 60%) required sample size was 46 patients. Secondary endpoints were PFS and OS. Results: 46 patients were enrolled. 17 patients (37%) were allocated to the favourable and 29 patients (63%) to the unfavourable profile. Patients resulted comparable for clinical characteristics (age, sex, ECOG PS, previous treatments, number of metastatic sites). Patients with the unfavourable profile showed 2 BRAF mutations, 3 PIK3CA exon 20 mutations, 18 cases of EGFR GCN &lt;2.6, 20 cases of HER-3 and 16 cases of IGF-1 overexpression respectively. RAS analysis of patients enrolled before the introduction of all RAS status (35 patients) revealed 1 N-RAS mutation (3%) in a patient already allocated to the unfavourable group for HER-3 overexpression. RR in the favourable and unfavourable group was 11/17 (65%) and 2/29 (7%) (p= 0.007) respectively. The favourable group also showed an improved median PFS (8 months vs. 3 months, p &lt;0.0001) and OS (15 months vs. 6 months, p &lt;0.0001). Conclusions: A beyond RAS selection may further improve clinical outcome. This approach may also allow an early switch to alternative treatment for unfavourable profile patients.
Age and ethnicity predict overall survival in patients with metastatic gastric cancer
Authors: D. Yang, C. Lenz, K. Togawa, G. Lurje, A. Pohl, P. C. Manegold, Y. Ning, S. G. Groshen, H. J. Lenz
Journal: Journal of Clinical Oncology (2008)

15500 Background: Patients diagnosed with metastatic gastric cancer have dismal outcome. There was a lack of established regimens to improve their survival. The prognostic role of gender, age and ethnicity on survival for patients with metastatic gastric cancer has not been determined in the U.S. It has been shown that Asians treated in Asia have overall a significant better outcome than Caucasians treated in Western world. The etiology of gastric cancer may differ among the different ethnic groups. These different etiologies include environmental factors, H.pylori infection and dietary factors which may lead to different genetic profiles of gastric cancer associated with different clinical outcome. Methods: Extracting data from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries, we compared overall survival for patients with metastatic gastric cancer by gender, age and ethnicity using multivariate Cox proportional hazards models. 15,228 patients (≥ 18 years) were identified from the years 1988- 2003. The ages of the males and females were categorized with <45, 45- 54, 55- 64, 65–74, and ≥75 years. Patients who were Native Americans, African Americans, Asians, Caucasians, and Hispanics were included. The models were adjusted for potential confouders including marital status at diagnosis, tumor site, treatment with radiation and/or surgery, and histology, and stratified by SEER registry sites and years of diagnosis. Results: Overall survival was decreased with age (p<0.001, Cox model). The median overall survival was 6 months in patients of ≤ 44 years compared to 2 months in patients who were ≥75 years. The difference of overall survival by ethnicity significantly was varied by sex (P for interaction = 0.01). Among males, Asian patients had longer overall survival, and African American patients had shorter overall survival compared to Caucasian patients (p=0.023). No significant difference in overall survival across ethnicity was found among females. Conclusions: This is the largest study of metastatic gastric cancer from SEER registries to show that age was a significant prognostic factor for overall survival in patients with metastatic gastric cancer. The influence of ethnicity on overall survival was dependent on sex. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Genentech™ BioOncology, ImClone Systems Incorporated, Merck, Pfizer Oncology, Response Genetics Genentech™ BioOncology, Merck, Pfizer Oncology, Roche, sanofi-aventis Dhont Family Foundation, NCI, NIH
NOTCH signaling in skeletal progenitors is critical for fracture repair
Authors: Cuicui Wang, Jason A. Inzana, Anthony J. Mirando, Yinshi Ren, Zhaoyang Liu, Jie Shen, Regis J. O’Keefe, Hani A. Awad, Matthew J. Hilton
Journal: Journal of Clinical Investigation (2016)

Fracture nonunions develop in 10%–20% of patients with fractures, resulting in prolonged disability. Current data suggest that bone union during fracture repair is achieved via proliferation and differentiation of skeletal progenitors within periosteal and soft tissues surrounding bone, while bone marrow stromal/stem cells (BMSCs) and other skeletal progenitors may also contribute. The NOTCH signaling pathway is a critical maintenance factor for BMSCs during skeletal development, although the precise role for NOTCH and the requisite nature of BMSCs following fracture is unknown. Here, we evaluated whether NOTCH and/or BMSCs are required for fracture repair by performing nonstabilized and stabilized fractures on NOTCH-deficient mice with targeted deletion of RBPjk in skeletal progenitors, maturing osteoblasts, and committed chondrocytes. We determined that removal of NOTCH signaling in BMSCs and subsequent depletion of this population result in fracture nonunion, as the fracture repair process was normal in animals harboring either osteoblast- or chondrocyte-specific deletion of RBPjk. Together, this work provides a genetic model of a fracture nonunion and demonstrates the requirement for NOTCH and BMSCs in fracture repair, irrespective of fracture stability and vascularity.
Inaccurate Reporting of Insulin Reimbursement—Reply
Authors: Jing Luo, Jerry Avorn, Aaron S. Kesselheim
Journal: JAMA Internal Medicine (2016)

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Membrane Immunofluorescence Reactions of Burkitt Lymphoma Cells From Biopsy Specimens and Tissue Cultures&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: G Klein, P Clifford, E Klein, R T Smith, J Minowada, F M Kourilsky, J H Burchenal
Journal: JNCI Journal of the National Cancer Institute (1967)

Five selected sera of patients with Burkitt's lymphoma, giving highly positive membrane immunofluorescence reactions against biopsy specimens of Burkitt cells, were negative when tested against normal bone marrow cells from donors of the same Burkitt lymphoma cells. One highly positive serum donor (Mutua) is now in chemotherapeutically induced regression and free of all signs of disease 30 months after therapy began. Mutua was selected for particular study. His sera gave highly positive reactions against biopsy specimens of Burkitt cells from 13 different donors, while the cells of 3 donors reacted more weakly. Leukoagglutination, lymphocytotoxicity, and membrane fluorescence tests against selected leukocytes and bone marrow cells of French donors with previously determined leukocyte groups gave negative results. These data indicate that the reactivity against the Burkitt target cells is probably not due to iso-antibody. Sera of 3 patients were highly positive against biopsy specimens of Burkitt cells during the first year after chemotherapeutically induced tumor regression, but had conspicuous decrease or even complete disappearance of reactivity during the second year. Tests on cells of established Burkitt tissue-culture lines Jijoye, B35M, EB3, and SL1 gave strong reactions with Mutua's serum. The reactivity of Mutua's serum against cells of these tissue culture lines was found to reside, at least in part, in the IgG fraction, as demonstrated by the use of a fluorescein-conjugated goat antiserum, directed against purified human IgG heavy chain. Three other lines of Burkitt origin, Kudi, Ogun, and Raji, were negative with Mutua's serum. Other established tissue culture lines, 7 derived from various acute leukemias arising in the United States, and 1 from the buffy coat of peripheral blood in a normal individual (Daniels), were all negative. Biopsy specimens from 2 African lymphosarcomas of non-Burkitt type, and bone marrow aspirates from 3 patients with acute leukemia arising in the United States were also negative with Mutua's serum.