tbuckley/cabot-search huggingface dataset:
Neuraminidase inhibitors during pregnancy and risk of adverse neonatal outcomes and congenital malformations: population based European register study
Authors: Sophie Graner, Tobias Svensson, Anna-Belle Beau, Christine Damase-Michel, Anders Engeland, Kari Furu, Anders Hviid, Siri Eldevik Håberg, Ditte Mølgaard-Nielsen, Björn Pasternak, Helle Kieler
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To evaluate the possible effects of exposure to neuraminidase inhibitors during embryo-fetal life with respect to adverse neonatal outcomes and congenital malformations. <b>Design</b>&nbsp;Population based multinational observational cohort study and meta-analysis. <b>Setting</b>&nbsp;National registers covering information on maternal healthcare, births, and prescriptions in Denmark, Norway, and Sweden and the EFEMERIS database from the Haute-Garonne district in France. <b>Participants</b>&nbsp;All women together with their singleton infants born between 1 January 2008 and 31 December 2010. Only infants born at 154 days of gestation or later were included. Infants were defined as exposed if the women filled a prescription during pregnancy for either of the two neuraminidase inhibitors oseltamivir or zanamivir. <b>Main outcomes</b>&nbsp;Low birth weight, low Apgar score, preterm birth, small for gestational age birth, stillbirth, neonatal mortality, neonatal morbidity, and congenital malformations. Crude and adjusted hazard ratios of preterm birth were estimated using Cox regression models. Crude and adjusted odds ratios for other outcomes were estimated by logistic regression models. <b>Results</b>&nbsp;The study included 5824 (0.8%) exposed women and their infants and 692 232 who were not exposed. Exposure to neuraminidase inhibitors in utero was not associated with increased risks of any of the investigated neonatal outcomes, including low birth weight (adjusted odds ratio 0.77, 95% confidence interval 0.65 to 0.91), low Apgar score (adjusted odds ratio 0.87, 0.67 to 1.14), preterm birth (adjusted hazard ratio 0.97, 0.86 to 1.10), small for gestational age birth (adjusted odds ratio 0.72, 0.59 to 0.87), stillbirth (adjusted odds ratio 0.81, 0.51 to 1.30), neonatal mortality (adjusted odds ratio 1.13, 0.56 to 2.28), and neonatal morbidity (adjusted odds ratio 0.92, 0.86 to 1.00). No increased risk of congenital malformations overall associated with maternal exposure was observed during the first trimester (adjusted odds ratio 1.06, 0.77 to 1.48). Similarly, no significantly increased risks of any of the outcomes were observed in an analysis restricted to oseltamivir alone. <b>Conclusions</b>&nbsp;This large multinational register study found no increased risks of adverse neonatal outcomes or congenital malformations associated with exposure to neuraminidase inhibitors during embryo-fetal life. The results support previously reported findings that the use of neuraminidase inhibitors is not associated with increased risks of adverse fetal or neonatal outcomes.
Dovitinib in first-line metastatic renal cell carcinoma and correlation of efficacy with tumor gene status: A phase II clinical trial.
Authors: Reuben James Broom, George Dranitsaris, Carol Fraser-Browne, Kerin Thompson, Steve Duffey, Georgia Wilson, Paul Oei, Jonathan Zwi, Mark James McKeage, Nicola Jane Mitchell, Fritha Hanning, Peter C.C. Fong
Journal: Journal of Clinical Oncology (2014)

4569 Background: Dovitinib is an anti-VEGFR tyrosine kinase inhibitor which also inhibits FGFR-1,-2,-3 and PDGFRβ. We studied its activity as 1st-line therapy in patients with metastatic clear-cell renal cell carcinoma (mCCRCC) and correlated genes related to its action mechanism with clinical outcomes. Methods: The 31 treatment naïve patients with mCCRCC enrolled in this single-arm, single-site, phase II study received dovitinib at 500mg 5 days on/2 days off until progression. An optional post-treatment biopsy was offered to study resistance mechanisms. The primary endpoint was progression free survival (PFS) using RECIST 1.1. Secondary endpoints included response rate and efficacy by gene status (FISH and DNA sequence). Results: Accrual occurred over 15 months from March 2012. Median patient age was 64 and 72% were male. ECOG performance status was 0 in 45% and 1 in 55%. Heng prognostic group was favorable risk in 38%, intermediate risk in 52% and poor risk in 10%. 38% had bone metastases. 4 patients stopped treatment due to toxicity and 1 patient withdrew. Median PFS was 6.2 months (inter quartile range: 3.3 to 8.2). Of 28 evaluable patients, best response was: PR (29%), SD (53%) and PD (18%). All-cause grade 3/4 adverse events (AE's) occurring in ≥5% of patients were: fatigue (16%), abdominal pain (13%), pancreatitis (10%), gout (7%), diarrhea (7%), bone pain (7%), hypercalcemia (7%), elevated lipase (7%) and pulmonary embolism (7%). Pre-treatment metastatic and primary tumor tissue was available from 93% and 54% of patients respectively. 6 patients donated post-progression tissue. Gene status (FISH) for FGFR-1,-2,-3, PDGFβ and PDGFRβ was available for 20 primary and 17 metastatic specimens. FGFR-1 showed a trend towards positive correlation between gene gain/amplification and response (Spearman's rho = 0.32, p = 0.17). FGFR-2, FGFR-3, PDGFRβ and PDGFβ showed no statistically significant associations. Conclusions: Dovitinib has activity in the first line setting of mCCRCC with a tolerable safety profile at the given dosing schedule. A non-significant correlation of this activity with FGFR-1 gene gain/amplification was seen and further study with a larger sample size is warranted. Clinical trial information: ACTRN12612000140853.
Cardiovascular Safety of Tocilizumab Versus Tumor Necrosis Factor Inhibitors in Patients With Rheumatoid Arthritis: A Multi‐Database Cohort Study
Authors: Seoyoung C. Kim, Daniel H. Solomon, James R. Rogers, Sara Gale, Micki Klearman, Khaled Sarsour, Sebastian Schneeweiss
Journal: Arthritis & Rheumatology (2017)

Objective While tocilizumab (TCZ) is known to increase low‐density lipoprotein (LDL) cholesterol levels, it is unclear whether TCZ increases cardiovascular risk in patients with rheumatoid arthritis (RA). This study was undertaken to compare the cardiovascular risk associated with receiving TCZ versus tumor necrosis factor inhibitors (TNFi). Methods To examine comparative cardiovascular safety, we conducted a cohort study of RA patients who newly started TCZ or TNFi using claims data from Medicare, IMS PharMetrics, and MarketScan. All patients were required to have previously used a different TNFi, abatacept, or tofacitinib. The primary outcome measure was a composite cardiovascular end point of hospitalization for myocardial infarction or stroke. TCZ initiators were propensity score matched to TNFi initiators with a variable ratio of 1:3 within each database, controlling for &gt;65 baseline characteristics. A fixed‐effects model combined database‐specific hazard ratios (HRs). Results We included 9,218 TCZ initiators propensity score matched to 18,810 TNFi initiators across all 3 databases. The mean age was 72 years in Medicare, 51 in PharMetrics, and 53 in MarketScan. Cardiovascular disease was present at baseline in 14.3% of TCZ initiators and 13.5% of TNFi initiators. During the study period (mean ± SD 0.9 ± 0.7 years; maximum 4.5 years), 125 composite cardiovascular events occurred, resulting in an incidence rate of 0.52 per 100 person‐years for TCZ initiators and 0.59 per 100 person‐years for TNFi initiators. The risk of cardiovascular events associated with TCZ use versus TNFi use was similar across all 3 databases, with a combined HR of 0.84 (95% confidence interval 0.56–1.26). Conclusion This multi‐database population‐based cohort study showed no evidence of an increased cardiovascular risk among RA patients who switched from a different biologic drug or tofacitinib to TCZ versus to a TNFi.
Bortezomib, Dexamethasone and Rituximab in Newly Diagnosed Patients with WaldenströM's Macroglobulinemia: Final Analysis of a Phase 2 Study after a Minimum Follow up of 6 Years
Authors: Maria Gavriatopoulou, Ramon Garcia-Sanz, Efstathios Kastritis, Pierre Morel, Marie-Christine Kyrtsonis, Evridiki Michalis, Zafeirios Kartasis, Xavier Leleu, Giovanni Palladini, Alessandra Tedeschi, Dimitra Gika, Giampaolo Merlini, Pieter Sonneveld, Meletios A Dimopoulos
Journal: Blood (2016)
Abstract P5-02-04: Study on over-diagnosis of high-precision breast cancer screening ∼ Consideration from epidemiological point of view
Authors: K Takebe, T Arai
Journal: Cancer Research (2017)

Abstract &amp;lt;Introduction&amp;gt; In breast cancer screening, it has been attempted to combine US with MMG. For relatively small breasts and dense breasts, there is the opinion that this combination is useful. On the other hand, the problem of over-diagnosis of breast cancer screening has been raised. We've been breast cancer screening with US/MMG combination method since 2005. The results were examined from the epidemiological point of view. &amp;lt;Subjects and Methods &amp;gt; Breast cancer discovery rate through US/MMG screening at our facility from 2005 to 2014 was considered. The medical examination was performed on 35,353 women. Kagawa Prefecture, in which our facility is located has had 100 percent breast cancer registration for more than 10 years. We have compared the breast cancer registration of 2013 with our examination results. &amp;lt;Results&amp;gt; Asymptomatic breast cancer detection rate in our breast cancer screening was 0.6%. ４６% of the detected cancer was DCIS. Low-grade DCIS (Van Nuys 1 and 2) accounted for three-quarters of DCIS. In invasive carcinoma, 10 mm or less of luminal A type was 17%, other luminal types 19%, non-luminal types 5% and unclassified 6%. If our facility's highly precise breast cancer medical examination were performed throughout Kagawa Prefecture, DCIS would be found in 860 cases, 10 mm or less of luminal A type found in 276, other luminal type found in 320 and non-luminal type found in 70 cases per year.Compared to the Kagawa Prefecture breast cancer registered in 2013, DCIS was 6.6 times larger than the registered data, 10 mm or less of luminal A 2.9 times larger, other luminal types 1.1 times larger, and non-luminal types 1.2 times larger. The differences between the registered data and our findings for DCIS and 10mm or less of luminal A type are remarkable. &amp;lt;Conclusion&amp;gt; With the US/MMG combination method, the detection rate of DCIS and 10 mm or less of luminal A type have been excessive. Many type of DCIS and tiny luminal A type must exist latently. When performing a high-precision breast cancer screening, it is necessary to note such over-diagnosis. Furthermore, it is also necessary to re-examine the pathology diagnostic criteria of DCIS. Citation Format: Takebe K, Arai T. Study on over-diagnosis of high-precision breast cancer screening ∼ Consideration from epidemiological point of view [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-02-04.
Are sarcomatoid lung cancers resistant tumors to conventional chemotherapy?
Authors: Marie Wislez, Thibault Vieira, Mony Ung, Martine Antoine, Isabelle Monnet, Pierre Bonnette, Aurelie Cazes, Michael Duruisseaux, Laure Belmont, Julien Mazieres, Jacques Cadranel, Nicolas Girard
Journal: Journal of Clinical Oncology (2013)

e19036 Background: Pulmonary sarcomatoid carcinomas (SC) account for about 0.4% of non-small cell lung carcinoma. These tumors have a poor prognosis due to high aggressiveness and maybe chemotherapy (CT) resistance. Methods: From 1995 to 2012, all consecutive patients with SC from 7 French hospitals and who underwent a 1 st -line chemotherapy were included. Clinical characteristics and effect of CT (best response by RECIST 1.1 and progression-free survival [PFS]) as well as overall survival (OS) were collected. Results: Ninety-seven patients were included. Mean age was 62±1 years, 70% were men, 84% smokers, 84% symptomatic, 25% had a stage III and 75% a stage IV disease. At 1 st -line, 73% received a platinum-based CT and 27% received a non-platinum-based CT. Progression (PR), stable disease (SD) and response (RR) rates were 69, 14.5 and 16.5%, respectively. For patients with platinum-based CT, PR, SD and RR rates were 69, 11 and 20%, respectively. RR rate was higher for platinum- than for non-platinum-based CT (p=0.018). Median PFS and OS were 2.0 mo [1.8 ; 2.3] and 6.7 mo [5.1 ; 8.2], respectively. No statistical difference in PFS (p=0.264) and OS (p=0.096) was observed between platinum and non-platinum based CT. In multivariate analysis, factors associated with better OS were disease control (HR=0.36 [0.21;0.59]), platinum-based CT (HR=0.92 [0.85;0.99]) and tobacco status (HR=0.92 [0.85 ; 0.99]). Conclusions: Two-thirds of patients with SC had early progression during 1 st -line CT. Platinum-based regimen increased response rate for a few and was an independent factor for better OS with a 8% decreased risk of death. Overall, SC appear to be chemoresistant suggesting that new therapeutic strategies based on a better knowledge of its carcinogenesis should be tested for these patients.
Racial Disparities in Medical Student Membership in the Alpha Omega Alpha Honor Society
Authors: Dowin Boatright, David Ross, Patrick O’Connor, Edward Moore, Marcella Nunez-Smith
Journal: JAMA Internal Medicine (2017)

Previous studies have found racial and ethnic inequities in the receipt of academic awards, such as promotions and National Institutes of Health research funding, among academic medical center faculty. Few data exist about similar racial/ethnic disparities at the level of undergraduate medical education.To examine the association between medical student race/ethnicity and induction into the Alpha Omega Alpha (AΩA) honor society.This study analyzed data from the Electronic Residency Application Service, the official service used by US medical students to apply to residency programs. A total of 4655 US medical students from 123 allopathic US medical schools who applied to 12 distinct residency programs associated with one academic health center in the 2014 to 2015 academic year were studied.Membership in the AΩA society among black, white, Hispanic, and Asian medical students.A total of 4655 unique applications were analyzed in the study (median age, 26 years; 2133 women [45.8%]). Overall, self-reported race/ethnicity in our sample was 2605 (56.0%) white (691 [71.5%] of AΩA applicants were white), 276 (5.9%) black (7 [0.7%] AΩA), 186 (4.0%) Hispanic (27 [2.8%] AΩA), and 1170 (25.1%) Asian (168 [17.4%] AΩA). After controlling for US Medical Licensing Examination Step 1 scores, research productivity, community service, leadership activity, and Gold Humanism membership, the study found that black (adjusted odds ratio [aOR], 0.16; 95% CI, 0.07-0.37) and Asian (aOR, 0.52; 95% CI, 0.42-0.65) medical students remained less likely to be AΩA members than white medical students. No statistically significant difference was found in AΩA membership between white and Hispanic medical students (aOR, 0.79; 99% CI, 0.45-1.37) in the adjusted model.Black and Asian medical students were less likely than their white counterparts to be members of AΩA, which may reflect bias in selection. In turn, AΩA membership selection may affect future opportunities for minority medical students.
Nab-paclitaxel plus either gemcitabine or simplified leucovorin and fluorouracil as first-line therapy for metastatic pancreatic adenocarcinoma (AFUGEM GERCOR): a non-comparative, multicentre, open-label, randomised phase 2 trial
Authors: Jean-Baptiste Bachet, Pascal Hammel, Jérôme Desramé, Aurélia Meurisse, Benoist Chibaudel, Thierry André, Philippe Debourdeau, Jérome Dauba, Thierry Lecomte, Jean-François Seitz, Christophe Tournigand, Thomas Aparicio, Véronique Guerin Meyer, Julien Taieb, Julien Volet, Amandine Monier, Franck Bonnetain, Christophe Louvet
Journal: The Lancet. Gastroenterology & hepatology (2017)
Antidepressants and benzodiazepines are linked to hip fracture in elderly people, finds study
Authors: Susan Mayor
Journal: BMJ (2017)

Older people with hip fracture are more likely to be taking antidepressants or benzodiazepines than the general elderly population, an observational study has found.

Hip fractures are very common in older people, and drugs that impair balance, such as psychotropic agents, are one risk factor. Previous studies have shown increased risk of falls and hip fractures in older people taking antidepressants but have …
ICARVS-study: A prospective cohort study to assess the incidence of venous thromboembolism in asymptomatic carriers of the FV:Q(506) mutation. Preliminary results
Authors: S Middeldorp, [No Value] Meinardi, Mmw Koopman, Ecm vanPampus, K Hamulyak, J vanderMeer, MH Prins, HR Buller
Journal: Blood (1997)
Phase 1 study of REGN1400 (anti-ErbB3) combined with erlotinib or cetuximab in patients (pts) with advanced non-small cell lung cancer (NSCLC), colorectal cancer (CRC), or head and neck cancer (SCCHN).
Authors: Kyriakos P. Papadopoulos, Alex A. Adjei, Drew Warren Rasco, Liming Liu, Richard J. Kao, Carrie M. Brownstein, A Thomas DiCioccio, Israel Lowy, Pamela Trail, Ding Wang
Journal: Journal of Clinical Oncology (2014)

2516 Background: REGN1400 (R) is a fully human mAb targeting ErbB3. Preclinically, dual inhibition of ErbB3 and EGFR confers augmented antitumor potency. This first-in-human dose escalation trial evaluates safety, tolerability, recommended phase 2 dose (RP2D), pharmacokinetics (PK) and anti-tumor activity of R alone or combined with erlotinib (E) or cetuximab (C) in NSCLC, CRC or SCCHN pts who progressed on prior E or C. Methods: This study used a 2-stage 3+3 design. R is administered IV Q2W at doses of 3, 10, or 20 mg/kg. Once safety of a monotherapy R dose level was established, subsequent pts enrolled directly into combination cohorts. Pts tolerating R monotherapy in cycle 1 (2 doses) could receive combination therapy thereafter. E and C are given per label, po QD or IV QW, respectively. Results: 22 pts [median age of 61 (range 38-78 yrs); M/F (15/7); ECOG PS 0/1 (5/17)] have been treated with R at 3 (n=8), 10 (n=8), and 20 mg/kg (n=6). Twelve pts received R monotherapy, and 20 pts received R combined with E or C. No protocol defined DLTs were observed. Ten treatment-related AEs (TRAEs) in 4 pts occurred with R monotherapy; 2 pts each had fatigue and vomiting. There were 64 TRAEs in 15 pts during combination therapy including rash (11) diarrhea (8), nausea (4), hypomagnesemia (3), increased AST, dry skin, fatigue and stomatitis (2 each). Four TRAE in 3 pts were grade ≥ 3; stomatitis, increased alk phos and pyrexia. There were 14 SAEs in 8 pts: pneumonia (3) and disease progression (3); and single events including dehydration, fatigue, nausea, pyrexia, respiratory failure, sepsis and vomiting. One pt required E dose reduction after addition of R. A pt with advanced tongue cancer who had progressed on C achieved a PR of 17 weeks duration with R + C. The PK profile of R showed linear and dose proportional kinetics; combination with E or C had no impact on R kinetics. Conclusions: R alone or combined with E or C was generally tolerated at the RP2D of 20 mg/kg Q2W. Combination therapy did not appear to potentiate any anti-EGFR related AEs. Enrollment into combination expansion cohorts is ongoing in SCCHN and CRC and will include pts who are naïve to EGFR inhibitors. Clinical trial information: NCT01727869.
Interferon‐γ‐induced insufficient autophagy contributes to p62‐dependent apoptosis of epithelial cells in chronic rhinosinusitis with nasal polyps
Authors: B‐F. Wang, P‐P. Cao, Z‐C. Wang, Z‐Y. Li, Z‐Z. Wang, J. Ma, B. Liao, Y‐K. Deng, X‐B. Long, K. Xu, H. Wang, H. Wang, M. Zeng, X. Lu, Z. Liu
Journal: Allergy (2017)

Autophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, and homeostasis. This study aimed to investigate the contribution of autophagy to the pathogenesis of CRS with nasal polyps (CRSwNP).The expression of autophagic proteins [microtubule-associated protein 1 light chain 3B (LC3B)-II, autophagy-related proteins (Atg), and Beclin 1], substrate proteins (p62 and ubiquitinated proteins), and apoptotic signaling molecules [cysteine-aspartic protease-3 and cysteine-aspartic protease-8, and poly-ADP-ribose polymerase] in the sinonasal mucosa and nasal epithelial cells (NECs) was detected by immunohistochemistry and Western blotting. Autophagic vacuoles were observed with transmission electron microscopy. BEAS-2B cells and NECs were treated with rapamycin, bafilomycin A1, or various cytokines. In some experiments, cultured NECs were transfected with small interfering RNA targeting p62 (sip62) or Atg5 (siAtg5). Cultured cells were analyzed with Western blotting and flow cytometry.Although autophagic protein expression and autophagic vacuole formation were increased in both eosinophilic and noneosinophilic CRSwNP, particularly in NECs, there was also an up-regulation of substrate proteins and apoptotic signaling molecules. IFN-γ, but not IL-4, IL-13, or IL-17A, simultaneously enhanced LC3B-II and p62 levels as well as cell apoptosis in BEAS-2B cells and/or normal NECs. Bafilomycin A1 up-regulated the levels of LC3B-II and p62 in polyp NECs and IFN-γ-treated normal NECs. IFN-γ-induced apoptosis of normal NECs was exaggerated by bafilomycin A1 and siAtg5. Sip62 suppressed apoptosis of polyp NECs and IFN-γ-treated NECs. IFN-γ protein levels were increased in both eosinophilic and noneosinophilic CRSwNP.IFN-γ induces activated but insufficient autophagy and thus contributes to a degree to p62-dependent apoptosis of NECs in CRSwNP.
Abstract P5-02-06: The impact of the introduction of breast cancer screening on a symptomatic breast cancer unit
Authors: BM Moloney, C Malone, K Sweeney, K Barry, R McLoughlin, A Larke, S Walsh, AM O Connell, R Ennis, PA McCarthy, MJ Kerin
Journal: Cancer Research (2017)

Abstract This abstract was not presented at the symposium.
Maintaining the Benefits of Pulmonary Rehabilitation. The Holy Grail
Authors: Carolyn L. Rochester, Martijn A. Spruit
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

[Rochester, Carolyn L.] Yale Univ, Sch Med, Sect Pulm Crit Care & Sleep Med, 333 Cedar St, New Haven, CT 06520 USA. [Rochester, Carolyn L.] VA Connecticut Healthcare Syst, Dept Internal Med, West Haven, CT 06516 USA. [Spruit, Martijn A.] Ctr Expertise Chron Organ Failure, CIRO, Dept Res & Educ, Horn, Netherlands. [Spruit, Martijn A.] Hasselt Univ, Fac Med & Life Sci, REVAL, Diepenbeek, Belgium. [Spruit, Martijn A.] Maastricht Univ, Med Ctr, NUTRIM Sch Nutr & Translat Res Metab, Maastricht, Netherlands.
Unusual Site Thrombosis: Focus on Myeloproliferative Neoplasms with Splanchnic or Cerebral Venous Thrombosis
Authors: Serena Rupoli, Lucia Canafoglia, Gianluca Svegliati Baroni, Michele Gironella, Giorgia Micucci, Irene Federici, Massimo Offidani, Gaia Goteri, Alessandro Fiorentini, Alessandra Riva, Lidia Da Lio, Leandro Provinciali, Anna Rita Scortechini, Elisa Honorati, Pietro Leoni
Journal: Blood (2016)