tbuckley/cabot-search huggingface dataset:
Incidence and Prognostic Impact of Secondary Neoplasia after High Dose Therapy Supported By Autologous Stem Cell Transplantation in Follicular Lymphoma. a Long Term Follow-up Analysis from the Geltamo Registry
Authors: ANA Jimenez Ubieto, Carlos Grande, Dolores Caballero, Lucrecia Yañez, Silvana Novelli, Miguel-Teodoro Hernández, Marina Manzanares, Reyes Arranz, José Javier Ferreiro, Sabella Bobillo, Santiago Mercadal, Andrea Galeo, Javier Lopez-Jimenez, Jose Maria Moraleda, Carlos Vallejo, Carmen Albo, Elena Pérez, Carmen Marrero, Laura Magnano, Luis Palomera, Isidro Jarque, Pilar Martínez-Sánchez, Alejandro Martín, Erika Coria, Armando López-Guillermo, Antonio Salar, Juan José Lahuerta
Journal: Blood (2016)
The association of surgical margins and local recurrence in women with ductal carcinoma in situ treated with breast-conserving therapy: A meta-analysis.
Authors: Michael Luke Marinovich, Lamiae Azizi, Petra Macaskill, Les Irwig, Monica Morrow, Lawrence J. Solin, Nehmat Houssami
Journal: Journal of Clinical Oncology (2016)

1020 Background: There is no consensus on what constitutes adequate negative margins in breast-conserving surgery (BCS) for ductal carcinoma in-situ(DCIS). We systematically review the evidence on surgical margins in BCS for DCIS. Methods: Study-level meta-analysis of studies reporting local recurrence (LR) relative to microscopic margin status and threshold distance for negative margins. LR proportion was modelled using random-effects logistic meta-regression (frequentist) that dichotomised data using one margin distance, and network meta-analysis (Bayesian) that allows for multiple margin distances per study, adjusting for follow-up time. Results: Based on 33 studies (LR in 865 of 7,883), theodds of LR were associated with margin status (logistic: odds ratio (OR) 0.53 for negative vs positive/close [P<0.001]; network: OR=0.45 for negative vs positive). In logistic meta-regression models, relative to >0 or 1mm, ORs for 2mm (0.51), 3 or 5mm (0.42) and 10mm (0.60) thresholds showed comparable significant reductions in the odds of LR. Odds of LR did not differ between 2mm, 3 or 5mm, and 10mm (all P>0.40). Predicted probabilities of LR at 10 years were 18.1% (>0 or 1mm), 10.1% (2mm), 8.5% (3 or 5mm), and 11.7% (10mm). In the network analysis, ORs relative to positive margins for 2mm (0.32), 3mm (0.30) and 10mm (0.32) showed similar reductions in the odds of LR that were greater than for >0 or 1mm (0.45). There was weak evidence of lower odds at 2mm compared to >0 or 1mm (Relative OR=0.72, 95% credible interval [CrI] 0.47-1.08), and no evidence of a difference between 2mm and 10mm (Relative OR=0.99, 95% CrI 0.61-1.64). Adjustment for covariates (age; median recruitment year; and proportions with radiotherapy, endocrine therapy, or high grade DCIS), and analyses based only on studies using whole-breast radiotherapy, did not change findings. Conclusions: Negative margins in BCS for DCIS reduce the odds of LR; however, minimum margins distances above 2mm are not significantly associated with further reduced odds of LR in women receiving radiation.
Abstract 15552: Risk Factors for Postnatal Surgery in the Fetus With Borderline Small Left Heart
Authors: Elijah Bolin, Carmen Watrin, Olukayode Garuba, Carolyn Altman, Nancy Ayres, Shaine Morris
Journal: Circulation (2013)

Background:  The presence of mild to moderate hypoplasia of left sided structures in the fetus is commonly observed, but predictors for the need for single ventricle palliation have not been defined.   Objectives:  The aim of this study was to evaluate echocardiographic features associated with the need for any postnatal surgery, and specifically for single ventricle palliation in fetuses with mild to moderate aortic valve hypoplasia.   Methods:  We reviewed all fetal echocardiograms performed at    Results:  A total of 48 fetuses were identified. Postnatally, 29 underwent cardiac surgery; 12 had aortic arch advancement, 11 had coarctation repair, and 6 required stage I single ventricle palliation. There were 11 postnatal deaths; 4 required stage I palliation prior to death, one would have required stage I palliation but was placed on comfort care, and 6 had significant non-cardiac anomalies who were not surgical candidates. The strongest independent variable associated with outcome was a novel measurement of prenatal aortic valve z-score plus mitral valve z-score (AMZ). An AMZ cutoff of   -4.4 was 91% sensitive and 80% specific for survival without surgery (area under curve = 0.876, p    Conclusion:  AMZ is a novel measurement associated with outcomes in fetuses with mild to moderate aortic valve hypoplasia; AMZ scores using cutoffs of -6.4 and -4.4 are useful in predicting stage I palliation and survival without surgery, respectively. AMZ may be helpful in prenatal counseling.
Long-term outcome of breast cancer patients diagnosed ≤40 years according to breast cancer subtype in the absence of adjuvant systemic therapy: The PARADIGM initiative.
Authors: Gwen Dackus, Natalie D ter Hoeve, Mark Opdam, Willem Vreuls, Esther A Koop, Stefan M. Willems, Zsuzsanna Varga, Alicia Cordoba, Antien L Mooyaart, Emilie Groen, Annegien Broeks, Nikolas Stathonikos, Katarzyna Józwiak, Michael Hauptmann, Gabe S. Sonke, Elsken Van Der Wall, Sabine Siesling, Paul J. van Diest, Sabine C. Linn
Journal: Journal of Clinical Oncology (2017)

535 Background: Young age at breast cancer diagnosis is considered a poor prognostic factor. As a result, many treatment guidelines advice adjuvant systemic treatment for young patients. Answering prognostic questions on young patients has therefore become a challenge. The PARADIGM (PAtients with bReast cAncer DIaGnosed preMenopausally) project aims to assess the long-term outcome of women diagnosed with breast cancer ≤40 years in the absence of adjuvant systemic therapy, using real world data from the nationwide Netherlands Cancer Registry (NCR) coupled with tissue biobanking. Methods: All women ≤40 years, diagnosed in the Netherlands between 1989-2000 with a primary invasive, histologically proven, T any N 0 M 0 breast cancer, without adjuvant systemic treatment were identified through the NCR. Back then N 0 patients were considered low risk and did not receive adjuvant systemic treatment. Tissue specimens were revised by a team of dedicated breast pathologists. Cox regression was performed to estimate hazard ratios for recurrence-free (RFS) and overall survival (OS) according to immunohistochemical (IHC) subtype. Analyses were adjusted for grade, pathological T-stage, histological subtype and radiotherapy. Results: We included 2310 patients with a mean follow-up of 15.4 years (range 0-25 years). OS for the whole cohort was 68% and RFS 58.4% at 25 years. In total 740 deaths and 1043 recurrences were observed. Hormone receptor (HR)+/HER2+ patients had a significantly worse OS when compared to HR-HER2+ patients (adjusted Hazard Ratio 1.58; 95% confidence interval 1.05-2.38; p=0.029). No difference was observed between HR-HER2+ and the triple negative and HR+/HER2- subgroups at 25-years. RFS was similar for all IHC subtypes. Conclusions: In this large cohort of non-adjuvant systemically treated young breast cancer patients with long-term follow-up HR+/HER2+ patients have a significantly worse survival when compared to triple negative, HR-/HER2+ and HR+/HER2- patients. The latter three subtypes have similar OS at 25 years. Future molecular studies have been planned to distinguish the favorable from the unfavorable prognostic patients.
Baseline plasma HA in PDA versus healthy subjects and effects of PEGPH20 on plasma HA in PDA subjects treated with GEM/NAB.
Authors: Anas M. Fathallah, Marie Printz, Barry Sugarman, Steve Shuey, Xionghua W. Wu, Ya Huang, Dimitrios Chondros, Daniel C. Maneval, Rose E. Sekulovich
Journal: Journal of Clinical Oncology (2016)

e15699 Background: PEGylated recombinant human hyaluronidase (PEGPH20) degrades stromal and tissue hyaluronan (HA) in preclinical pancreatic ductal adenocarcinoma (PDA) models. From an ongoing phase 2 randomized study in subjects with Stage IV PDA treated with PEGPH20, gemcitabine (GEM) and nab-paclitaxel (NAB), we report plasma HA disaccharide concentrations at baseline and post PEGPH20 to evaluate: 1) differences in baseline plasma HA as compared to healthy volunteers, and 2) the kinetics of HA changes post PEGPH20. Methods: Baseline plasma HA from 68 PDA subjects and 24 healthy volunteers was compared using an unpaired Student’s t-test. The entire plasma HA time course of each subject in the phase 2 study was modeled using Non-Linear Mixed Effect modeling (NLME). The dynamics of plasma HA was captured with an indirect response model with zero order input and saturable output from the plasma compartment. Changes to plasma HA post dosing were driven by the enzymatic activity of the recombinant human hyaluronidase in plasma. To better estimate maximal response and EC50, data from subjects treated with either a single high or low PEGPH20 dose (50 or 1µg/kg) from a prior phase 1 study were added to the analysis. Data were fitted simultaneously with HA concentrations from healthy volunteers’ plasma to test whether baseline plasma HA concentrations in PDA subjects and healthy volunteers differ. A possible correlation between baseline plasma HA in PDA subjects and HA detected in pre-treatment tumor biopsies was also investigated. Results: Baseline plasma HA was 4.4-fold higher (p < 0.05) in PDA vs healthy subjects. Disease status was a statistically significant covariate in NLME (ΔOBJ > 3.85), reducing inter-individual variability and supporting acceptance of the null hypothesis. Baseline plasma HA did not differ in subjects with HA high vs low tumors as defined by IHC. On average PEGPH20 dosing increased plasma HA concentration by 14 fold within 2 - 6 hours and 213 fold by 24 hours post dose. Conclusions: Baseline plasma HA concentrations were elevated in PDA subjects and increased dramatically over the first 24 hr post PEGPH20 dosing, which may be a useful pharmacodynamic marker for PEGPH20 activity. Clinical trial information: NCT00834704, NCT01839487.
Gender differences in the risk of ischemic stroke associated with aortic atheromas circulation
Authors: Marco R. DiTullio, Ralph L. Sacco, Robert R. Sciacca, M.T. Savoia, I.V. Titova, G. Gaspard, Bernadette Boden-Albala, L.D.L. Santos, Shunichi Homma
Journal: Circulation (2000)
Correspondence on Lovell et al.: identification of chicken genes previously assumed to be evolutionarily lost
Authors: Susanne Bornelöv, Eyal Seroussi, Sara Yosefi, Ken Pendavis, Shane C. Burgess, Manfred Grabherr, Miriam Friedman-Einat, Leif Andersson
Journal: Genome biology (2017)

Through RNA-Seq analyses, we identified 137 genes that are missing in chicken, including the long-sought-after nephrin and tumor necrosis factor genes. These genes tended to cluster in GC-rich regions that have poor coverage in genome sequence databases. Hence, the occurrence of syntenic groups of vertebrate genes that have not been observed in Aves does not prove the evolutionary loss of such genes. Please see related Research article: http://dx.doi.org/10.1186/s13059-014-0565-1 and Please see response from Lovell et al: https://www.dx.doi.org/10.1186/s13059-017-1234-y
Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer
Authors: K. Blackwell, P. Gascon, C.M. Jones, A. Nixon, A. Krendyukov, R. Nakov, Y. Li, N. Harbeck
Journal: Annals of Oncology (2017)

Following the functional and physicochemical characterization of a proposed biosimilar, comparative clinical studies help to confirm biosimilarity by demonstrating similar safety and efficacy to the reference product in a sensitive patient population.LA-EP2006 is a proposed biosimilar that has been developed for pegfilgrastim, a long-acting form of granulocyte colony-stimulating factor for the prevention of neutropenia. The current analysis reports data pooled from two independent, multinational, prospective, randomized, controlled, double-blind phase III studies of similar design comparing the safety and efficacy of reference pegfilgrastim with LA-EP2006 in patients with breast cancer receiving myelotoxic (neo)adjuvant TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy and requiring granulocyte colony-stimulating factor.A total of 624 patients were randomized in the PROTECT-1 and PROTECT-2 studies (NCT01735175; NCT01516736) (LA-EP2006: n = 314; reference: n = 310). Baseline characteristics of patients were well balanced across treatment groups. The primary end point, mean duration of severe neutropenia in the first chemotherapy cycle was similar in both the LA-EP2006 and reference groups (1.05 ± 1.055 days versus 1.01 ± 0.958 days), with a treatment difference of - 0.04 days [95% confidence interval (CI): -0.19 to 0.11] that met the equivalence criteria (the 95% CI were within the defined margin of ±1 day). Secondary end points, such as the nadir of absolute neutrophil count and the incidence of febrile neutropenia, were also similar between LA-EP2006 and reference pegfilgrastim. The safety and tolerability profile of LA-EP2006 was similar to that observed with reference pegfilgrastim, and there were no reports of neutralizing antibodies.This pooled analysis confirms, as a part of totality of evidence approach, that the proposed biosimilar pegfilgrastim LA-EP2006 has a comparable efficacy and safety profile to reference pegfilgrastim in patients with breast cancer receiving TAC chemotherapy.NCT01735175 and NCT01516736.
Eosinophils Localize to Nerves in Patients with IBD Through Specifc Neurally Expressed Adhesion Molecules and Chemoattractants
Authors: CM Smyth, R Morgan, R Cummins, P Smith, O Shiels, FE Murray, RW Costello
Journal: Endoscopy (2004)

Introduction: The role of the eosinophil, which is a common inflammatory cell in inflamed gastrointestinal mucosa in inflammatory bowel disease (IBD) is uncertain. We have previously shown that eosinophils specifically localize to nerves in patients with IBD. The aim of this study was to define the mechanism of this localization.
Palonosetron or granisetron for prevention of CINV in patients with breast cancer receiving dexamethasone and fosaprepitant following anthracycline plus cyclophosphamide (AC) regimen.
Authors: Koji Matsumoto, Masato Takahashi, Kazuhiko Sato, Toshimi Takano, Yasuaki Ryushima, Mihoko Doi, Kenjiro Aogi, Kimiko Fujiwara, Kenji Tamura, Mitsuchika Hosoda, Shinya Tokunaga, Akitaka Makiyama, Kaisuke Miyamoto, Yasuo Hozumi, Kazuhiro Yanagihara, Chiyo K. Imamura, Yasutaka Chiba, Shinichiro Nakamura, Toshiaki Saeki
Journal: Journal of Clinical Oncology (2015)

9598 Background: Superiority of palonosetron to granisetron is uncertain, for patients with breast cancer receiving both steroid and NK1 inhibitor against CINV caused by AC regimen. Methods: We conducted a randomized double-blind active-controlled study. 341 chemo-naïve patients treated with AC regimen were randomized 1:1 to either (1) palonosetron 0.75 mg + dexamethasone + fosaprepitant or (2) granisetron 1mg + dexamethasone + fosaprepitant. Stratification factor was age ( < / > 55 yrs) and type of anthracycline (epirubicin / doxorubicin). Patients recorded episodes of emesis, nausea and rescue medication using a formed diary during 0 -120 hrs post-chemotherapy. Primary endpoint was complete response (CR = no emesis and no rescue medication) in delayed phase ( > 24 -120 hrs). Secondary endpoints include CR in acute (0-24 hrs) and overall (0 - 120hrs) phase. Nausea and emesis in acute, delayed, or overall phase was also evaluated. Treatment comparisons were performed using chi-square test with Yates' continuity correction. Results: From Dec. 2012 to Oct. 2014, 326 evaluable patients were enrolled with comparable characteristics across groups; median age 54, 87 % of patients received epirubicin, 71 % of patients were light or no drinkers, 71 % of patients had no motion sickness, and 52 % of patients had morning sickness. CR rates were similar for patients treated with palonosetron and granisetron in delayed (62.3 vs 60.4 %; p = 0.8), acute (75.9 vs 73.2 %), and overall (54.9 vs 54.9 %) phase, respectively. Palonosetron reduced nausea (59.9 vs 72 %; p = 0.029) and emesis (10.5 vs 17.7 %; p = 0.088) in delayed phase. Adverse events occurred at similar rates across both groups. Conclusions: Although nausea and emesis in delayed phase was reduced, palonosetron at highest effective dose did not prove superiority to granisetron for prevention of CINV in patients with breast cancer receiving dexamethasone and fosaprepitant following AC regimen. Three drugs combination with steroid, 5-HT3 receptor antagonist, and NK1 receptor antagonist did not achieve CR in almost half of patients in this population. A new class of agents is needed. Clinical trial information: UMIN000008897.
HIV persistence: clonal expansion of cells in the latent reservoir
Authors: Kyungyoon J. Kwon, Robert F. Siliciano
Journal: Journal of Clinical Investigation (2017)

While antiretroviral therapy (ART) can reduce HIV-1 to undetectable levels, the virus generally reappears if treatment is stopped. Resurgence of the virus is due to the reactivation of T cells harboring latent integrated provirus, and recent studies indicate that proliferation of these latently infected cells helps maintain the HIV-1 reservoir. In this issue of the JCI, Lee et al. evaluated CD4+ T cell subsets to determine whether certain populations are more likely to harbor full-length, replication-competent provirus. The authors identified an enrichment of clonally expanded Th1 cells containing intact HIV-1 proviruses, suggesting that this polarized subset contributes to the persistence of the reservoir. Strategies to target these provirus-harboring cells need to be considered for future therapies aimed toward HIV-1 cure.
Marginal bone loss around non-submerged implants is associated with salivary microbiome during bone healing
Authors: Xiao-Bo Duan, Ting-Xi Wu, Yu-Chen Guo, Xue-Dong Zhou, Yi-Ling Lei, Xin Xu, An-Chun Mo, Yong-Yue Wang, Quan Yuan
Journal: International Journal of Oral Science (2017)

Marginal bone loss during bone healing exists around non-submerged dental implants. The aim of this study was to identify the relationship between different degrees of marginal bone loss during bone healing and the salivary microbiome. One hundred patients were recruited, and marginal bone loss around their implants was measured using cone beam computed tomography during a 3-month healing period. The patients were divided into three groups according to the severity of marginal bone loss. Saliva samples were collected from all subjected and were analysed using 16S MiSeq sequencing. Although the overall structure of the microbial community was not dramatically altered, the relative abundance of several taxonomic groups noticeably changed. The abundance of species in the phyla Spirochaeta and Synergistetes increased significantly as the bone loss became more severe. Species within the genus Treponema also exhibited increased abundance, whereas Veillonella, Haemophilus and Leptotrichia exhibited reduced abundances, in groups with more bone loss. Porphyromonasgingivalis, Treponemadenticola and Streptococcus intermedius were significantly more abundant in the moderate group and/or severe group. The severity of marginal bone loss around the non-submerged implant was associated with dissimilar taxonomic compositions. An increased severity of marginal bone loss was related to increased proportions of periodontal pathogenic species. These data suggest a potential role of microbes in the progression of marginal bone loss during bone healing. Certain populations of bacteria found in saliva during dental implant procedures are associated with implant failure and bone loss. In non-submerged dental implant surgery, missing teeth are replaced with prosthetic teeth attached to screws implanted into bone. While these procedures are largely safe with predictable outcomes, some patients show bone loss around the implant site. Quan Yuan of Sichuan University, China, and colleagues analysed the bacterial content of saliva from 100 patients and found that the proportions of specific bacterial species in the samples bore significant correlation to the amount of bone loss the patients suffered. The team's findings indicate that certain species of bacteria may be associated with poor dental surgery outcomes and provide a starting point for researchers investigating dental implant rejection.
One in six elderly people is subjected to abuse, study finds
Authors: Anne Gulland
Journal: BMJ (2017)

One in six older adults experiences some kind of abuse, a meta-analysis of elder abuse has found.1

Published in the Lancet Global Health , the study found that 141 million adults worldwide aged over 60 were subjected to psychological abuse (11.6%), financial abuse (6.8%), neglect (4.2%), physical abuse (2.6%), or sexual abuse (0.9%).

The meta-analysis of 52 publications from countries around the world, including Canada, Germany, India, Iran, and the UK, found considerable variation between countries. For example, 14% of …
Addition of Obinutuzumab to Ibrutinib Enhances Depletion of CLL Cells in the Peripheral Blood and Bone Marrow after 1 Month of Combination Therapy: Initial Results from the Bloodwise TAP Iciclle Extension Study
Authors: Andy C Rawstron, Talha Munir, Samuel Muñoz-Vicente, Kristian Brock, Francesca J Yates, Rebecca Bishop, Surita Dalal, Ruth Mary de Tute, Adrian Bloor, Oonagh M Sheehy, Andrew R. Pettitt, Christopher P Fox, Christopher Fegan, Stephen Devereux, Donald Macdonald, Peter Hillmen
Journal: Blood (2016)
Do Patients with Reversible Haemorrhoidal Prolapse have fewer Complications after Stapled Haemorrhoidectomy than those with Permanent Prolapse
Authors: J Roy, M Katory, S Brown
Journal: Endoscopy (2004)

Aims: Milligan Morgan haemorrhoidectomy is the traditional operation for haemorrhoids with significant external component. Circular staples are alternative method of treatment in this group of patients. Here we audit complications after stapled haemorrhoidectomy in patients with and without permanent haemorrhoidal prolapse.