tbuckley/cabot-search huggingface dataset:
Surgical management of breast cancer in BRCA mutation carriers: A single centre experience
Authors: A. Fachinetti, C. Chiappa, S. Vischi, R. Roesel, L. Ambrosiani, I. Carnevali, M.G. Tibiletti, F. Rovera
Journal: Annals of Oncology (2019)

Background: The optimal local therapy for women with BRCA-associated breast carcinoma remains controversial, and still controversial is the prognostic role of controlateral prophylactic mastectomy (PCM). The aim of this study was to investigate the role of risk reductive surgery in BRCA patients. Methods: The authors conducted a retrospective review of 374 women with breast cancer who were tested for BRCA1 and BRCA2 genetic mutations at the Breast Unit of ASST Settelaghi - University of Insubria Varese between 2006 and 2016. Results: Among the 374 women who underwent genetic testing for BRCA mutation, 70 were found to have a BRCA1 mutation and 58 BRCA2. Among the patients we analyzed 88 women with BRCA1-2 mutation undergoing breast surgery in our Institute. The median age was 44, the median follow-up was 104 months. The overall survival of the treated group was 89,7% at 10 years and down to 77% for a longer follow-up. Analyzing the survival curves in relation to the type of surgery performed, there has not emerged any statistically significant difference in terms of OS among patients treated with conservative surgery compared to patients treated with mastectomy. We analyzed the OS of the group undergoing a PCM compared to the group that underwent no reductive risk surgery. The curves demonstrate that at a median follow-up of 120 months, patients undergoing a PCM appear to have better prognosis although not statistically significant but the benefit is cancelled by going forward with the follow-up years. Survival of 92.9% at 120 months in the PCM group, survival of 87.5% for patients not treated with risk reductive surgery [Breslow (Generalized wilcoxon) p = 0.577]. Conclusions: In the recent literature PCM was shown to reduce the incidence of contralateral breast cancer, but there is insufficient evidence that PCM improves survival, and further studies are recommended. Legal entity responsible for the study: Senology Research Center, Department of Surgical Sciences and Human Morphology, University of Insubria (Varese-Como), Varese, Italy. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
AN UNEXPECTED CAUSE OF CHOLANGITIS
Authors: L Venezia, P Cortegoso Valdivia, S Rizza, CG De Angelis
Journal: Endoscopy (2019)

A 57-year-old man with unremarkable previous medical history presented with acute cholangitis (bilirubin T/D 4,5/3,8 mg/dL, ALP 805 UI/I, GGT 203 UI/I). CT abdomen showed liver cirrhosis along with hypodense irregular filling defects in a dilated common hepatic duct up to the confluence, with upstream dilation of the intrahepatic ducts. A subsequent ERCP with IDUS and direct peroral cholangioscopy was performed, and the findings supported the suspicion of biliary papillomatosis. Intraductal biopsies showed papillary proliferations with focal high grade dysplasia and no signs of stromal invasion, thus confirming the final diagnosis of intraductal papillary neoplasm (IPN) BillN-3. Biliary IPN is a very rare disease, characterized by the presence of intraluminal papillary tumors of the intra- and/or extra hepatic bile ducts, with a distinctive papillary proliferation of billiary epithelial cells around a slender fibrovascular stalk. It potentially affects any site of the biliary tree, including the gallbladder. It is more common in men (M: F 2: 1) in the 6 – 7th decade, with a slow progression but with a high rate of malignant transformation (approximately 41%). The most common clinical manifestations are recurrent abdominal pain or discomfort, repeated relapsing cholangitis and cholestasis. The therapy is mainly surgical, with resection in localized disease; diffuse or recurrent disease requires pancreatoduodenectomy or liver transplantation in selected cases.
The Role of Early-Phase Design—Letter
Authors: Mark J. Ratain
Journal: Clinical Cancer Research (2019)

Conaway and Petroni suggest that the choice of phase I design “substantially enhances the proportion of effective agents that have successful phase III trials (1).” This conclusion is based on first simulating various phase I designs aimed at determining the MTD for populations of hypothetical new agents, followed by a single-arm phase II trial of varying size, followed by a phase III trial. Unfortunately, the simulation relies on historical and outdated paradigms for development of cytotoxic antineoplastic agents, rather than well-established principles of clinical pharmacology and drug development used outside of oncology.The use of the historical oncology paradigm leads to several incorrect assumptions. The authors assume that as toxicity increases, efficacy increases. While this may be true for cytotoxic chemotherapy, it is not expected to be true for modern oncology drugs, where incremental increases in dose may have no incremental increase in efficacy and only lead to incremental toxicity due to off-target effects. In this context, the therapeutic index decreases as the dose is increased beyond that achieving maximal efficacy. The authors' failure to recognize the potential for a flat dose–response curve is particularly surprising, given that one of their cited references makes this explicit point for pembrolizumab, which they used as “a concrete example” (2).This concern is not only relevant for other immunotherapeutics, but for modern small molecules as well.A recent analysis of all patent-protected oral drugs demonstrated that the majority of drugs are labeled at too high a dose (3). Thus, despite the successful completion of the drug development process, patients may experience unnecessary toxicity due to our reliance on historical drug development paradigms that are no longer pharmacologically appropriate.In this context, I would encourage biostatisticians and others interested in the design of early clinical trials to focus their efforts on a different paradigm, one in which the optimal dose can only be determined by randomized dose-ranging phase II and III trials (4, 5). Despite the widespread use of this paradigm in other therapeutic areas, there has been little effort to modify phase I oncology designs, which should aim to define a range of doses for phase II investigation. Hopefully we can redefine success as efficacy without severe toxicity, rather than continuing to accept high rates of severe toxicity that compromise the quality of life of patients with cancer and drive up the cost of oncology care.See the Response, p. 3191M.J. Ratain is an employee of Value in Cancer Care Consortium; reports receiving commercial research grants from AbbVie and Genentech; is a consultant/advisory board member for Aptevo, Cyclacel, AbbVie, Amgen, Ascentage, BioMarin, Elion Oncology, Genentech, Portola Pharmaceuticals, and Shionogi; and reports receiving other remuneration from multiple generic pharmaceutical companies for expert testimony and patent litigation consulting. No other potential conflicts of interest were disclosed.
THREADING THE NEEDLE: DIAGNOSTIC YIELD OF ENDOSCOPIC ULTRASOUND GUIDED FINE NEEDLE ASPIRATION IN REAL WORLD CLINICAL PRACTICE
Authors: C Clifford, C Moran, G Harkin, M Hussey, N McGettigan, GC Harewood, D Cheriyan, S Sengupta
Journal: Endoscopy (2019)

The primary aim was to assess diagnostic yield of solid pancreatic lesions. Secondary outcomes include: assessing the number of passes performed and the presence of trainees on diagnostic yield.
<i>Notes from the Field:</i> Measles Outbreaks from Imported Cases in Orthodox Jewish Communities — New York and New Jersey, 2018–2019
Authors: Robert McDonald, Patricia Schnabel Ruppert, Maria Souto, Dylan E. Johns, Kevin McKay, Noelle Bessette, Lissette X. McNulty, Jennifer E. Crawford, Patrick Bryant, Maria Cecilia Mosquera, Sonya Frontin, Tatiana Deluna-Evans, Daniel E. Regenye, Elizabeth F. Zaremski, Vanessa J. Landis, Bonnie Sullivan, Brian E. Rumpf, Judi Doherty, Kathryn Sen, Eric Adler, Lisa DiFedele, Stephanie Ostrowski, Christine Compton, Elizabeth Rausch-Phung, Irina Gelman, Barbara Montana, Debra Blog, Bradley J. Hutton, Howard A. Zucker
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

On October 1, 2018, the Rockland County (New York) Department of Health (RCDOH) alerted the New York State Department of Health (NYSDOH) of an unvaccinated teenaged traveler with diagnosed measles.During the next 17 days, RCDOH learned of an additional six unvaccinated travelers with measles.On October 24, 2018, the Ocean County (New Jersey) Health Department alerted the New Jersey Department of Health (NJDOH) of a case of measles in an international traveler, with rash onset October 17.The unvaccinated travelers reported recent travel in Israel, where an outbreak of approximately 3,150 cases of measles is ongoing (1).Investigations during October 1, 2018-April 30, 2019, identified 242 laboratory-confirmed and epidemiologically linked measles cases in New York, excluding New York City, and during October 17, 2018-November 30, 2018, identified 33 in New Jersey (Figure).The cases of measles were primarily in members of orthodox Jewish communities.
PROSPECTIVE COMPARISON OF AN ADULT, AN INTERMEDIATE PEDIATRIC AND A LONG PEDIATRIC COLONOSCOPE IN THE TRAINING PROCESS OF GASTROINTESTINAL FELLOWS TO ACHIEVE HIGH-QUALITY COLONOSCOPIC PRACTICE
Authors: G Tribonias, G Lyrakos, G Penesis, D Charisis, N Daferera, B Lykiardopoulos, K Al-Shaheen, H Hjortswang
Journal: Endoscopy (2019)

Few data are available on the influence of colonoscope length and diameter for trainees, which could affect both the training process and colonoscopy quality. We conducted this prospective observational cohort study to investigate which scope is more suitable for starting the colonoscopy training apropos technical competence, quality indicators and patient's comfort during diagnostic colonoscopy.
PREDICTIVE RULES FOR OPTICAL DIAGNOSIS OF ≤10 MM COLORECTAL POLYP: BASIC VALIDATION
Authors: C Hassan, R Bisschops, P Bhandari, E Coron, H Neumann, O Pech, L Correale, A Repici
Journal: Endoscopy (2019)

To in vivo predict colorectal polyp histology, the BASIC classification incorporates both morphological and pit/vessel descriptors domains. To define the new BASIC classes for adenomatous and hyperplastic polyps, we analytically assessed the strength of predictions of these descriptors individually and in combination.
The cleavage of gasdermin D by caspase-11 promotes tubular epithelial cell pyroptosis and urinary IL-18 excretion in acute kidney injury
Authors: Naijun Miao, Fan Yin, Hongyan Xie, Yanzhe Wang, Yiang Xu, Yang Shen, Dan Xu, Jianyong Yin, Bao Wang, Zhuanli Zhou, Qian Cheng, Panpan Chen, Hong Xue, Li Zhou, Jun Liu, Xiaoxia Wang, Wei Zhang, Limin Lu
Journal: Kidney International (2019)
A cost-utility analysis of administration schedules of G-CSF for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer: Economic evaluation alongside the REaCT-G trial
Authors: B. Basulaiman, A.A. Awan, J. Hilton, D. Fergusson, C. Stober, L. Vandermeer, D. Saunders, M. Clemons, K. Thavorn
Journal: Annals of Oncology (2019)

Background: Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost. The optimal duration of filgrastim as primary FN prophylaxis in early stage breast cancer (EBC) patients is unknown. We compared the cost-effectiveness of 5, 7 or 10 days of filgrastim offered for primary FN prophylaxis. Methods: We conducted a cost-utility analysis from the perspective of Canada's health care system using a decision tree to evaluate the costs and quality-adjusted life years (QALYs) based on the results of the REaCT G study. In this study EBC patients who were to receive adjuvant chemotherapy were randomized to 5 versus 7 or 10 days of filgrastim as primary FN prophylaxis. Using EQ-5D-5L measures from patients at baseline, after one cycle and at the completion of chemotherapy, along with the cost of complications of febrile neutropenia and treatment-related hospitalization from the provincial database, we determined incremental cost-effectiveness ratio (ICER) for the 7 or 10 days of filgrastim compared to 5 days. Both deterministic and probabilistic sensitivity analyses were carried out. Results: From 464 patients on the REaCT G trial showed that 5 & 7 days compared to 10 days filgrastim were associated with lower costs and a slight decrease in QALYs. Compared to 5 days of filgrastim, 10 days was associated with an increase cost $3,763 and 0.019 QALYs with ICER of $198,052, and 7 days of filgrastim led to a rise in cost by $2,461 and QALYs by 0.004 with ICER of $615,250. The probabilistic sensitivity analysis showed that cost-effectiveness results were uncertain. At commonly willingness to pay threshold of $50,000/QALY, probabilities that 5, 7 and 10 days filgrastim are cost-effective were 48%, 35%, and 18%, respectively. Conclusions: We conclude that shorter schedules of filgrastim provide cost savings with a slight decrease in QALY. The schedule of filgrastim prophylaxis that would be considered cost-effective depends on the willingness of the payer. Legal entity responsible for the study: Mark Clemons. Funding: REaCT Program and Cancer Care Ontario. Disclosure: All authors have declared no conflicts of interest.
Abstract P345: Short Sleep Duration is Associated With Atrial Fibrillation in a Clinical Cohort
Authors: Michael V Genuardi, Aisha Rasool Saand, Rachel P Ogilvie, Jared W Magnani, Sanjay R Patel
Journal: Circulation (2018)

Introduction: Patients who self-report short sleep duration are thought to have a higher risk of atrial fibrillation (AF), but objective data are lacking and it is not clear if this association is independent of sleep apnea. In this cross-sectional investigation, we evaluated the association between objectively measured sleep duration and AF in patients undergoing diagnostic sleep study. Methods: We evaluated all 30,572 patients who underwent in-laboratory diagnostic sleep study at one of six centers within the University of Pittsburgh Medical Center system from March 1999 to December 2015. Total sleep time (TST), apnea hypopnea index (AHI), percent sleep with oxygen saturation &lt; 90% (Per90), and cardiac rhythm on overnight EKG were extracted from sleep study reports using automated algorithms. Multivariable linear regression was used to model TST as a function of rhythm accounting for age, sex, body mass index (BMI) and sleep apnea severity using both AHI and Per90. We also performed a sensitivity analysis using patients whose AF status was confirmed by an inpatient or outpatient ICD-9 code at any point up to one day prior to the date of the sleep study. Results: The cohort was 52.0% female, aged 50.8±14.6 years (mean ± std dev), had a BMI of 33.7 ± 8.7 kg/m 2 , and an AHI of 17.4 ± 22.6 events/hr. Of the 30,572 patients, 369 (1.2%) had AF, 60 had a paced rhythm, 28,844 were in sinus, and 1299 had unclear rhythm. After adjusting for age and sex, TST was lower by 34 minutes (95% confidence interval, 26-42) in patients in AF compared to those in sinus rhythm. After further adjustment for BMI, AHI and Per90, TST was 28 minutes (18-38) lower for those in AF. The TST difference between patients in AF and sinus was primarily related to reduction in stage 2 non-REM sleep; AF patients had 32 minutes (22-41) less stage 2 sleep after adjustment. In a sensitivity analysis limited to 268 AF subjects with at least one AF diagnostic code and 26,239 sinus rhythm subjects without an AF diagnostic code, TST was 29 minutes (17-41) shorter in AF patients after adjustment. Conclusion: After accounting for differences in demographics and sleep apnea severity, patients with AF sleep about half an hour less on objective assessment. Our findings support an association between short sleep and AF. Future prospective studies are needed to determine if short sleep may be a novel mechanism for the development of AF.
FEWER COMPLICATIONS FOLLOWING PERCUTANEOUS-TRANSHEPATIC-ENDOSCOPIC RENDEZVOUS PROCEDURES COMPARED TO PERCUTANEOUS TRANSHEPATIC CHOLANGIOGRAPHY ALONE
Authors: A Bokemeyer, F Müller, H Niesert, M Brückner, D Bettenworth, T Nowacki, T Beyna, H Ullerich, F Lenze
Journal: Endoscopy (2019)

Biliary drainage can be challenging in cases of refractory bile duct obstruction and percutaneous-transhepatic-endoscopic rendezvous procedures (PTE-RVs) might facilitate biliary drainage even in these cases This study evaluated the safety and the technical success of PTE-RVs in comparison to those of percutaneous transhepatic cholangiografies (PTCs) for biliary drainage.
ENDOSCOPIC RADIOFREQUENCY ABLATION FOR PALLIATIVE TREATMENT OF HILAR CHOLANGIOCARCINOMA
Authors: AL Santos, F Vilas-Boas, R Morais, P Pereira, G Macedo
Journal: Endoscopy (2020)

Endoscopic radiofrequency ablation (RFA) can be an option, in unresectable perihilar cholangiocarcinoma (PC), for preventing stent occlusion and increasing overall survival.
The role of extracellular vesicles from different origin in the microenvironment of head and neck cancers
Authors: Changqing Xie, Ning Ji, Zhangui Tang, Jing Li, Qianming Chen
Journal: Molecular Cancer (2019)

The proliferation and metastasis ability of tumors are mediate by the "mutual dialogue" between cells in the tumor microenvironment (TME). Extracellular vesicles (EVs), mainly exosomes and microvesicles, play an important role in achieving intercellular substance transport and information transfer in the TME. Initially considered "garbage dumpsters" and later referred to as "signal boxes", EVs carry "cargo" (proteins, lipids, or nucleic acids) that can redirect the function of a recipient cell. Currently, the molecular mechanisms and clinical applications of EVs in head and neck cancers (HNCs) are still at an early stage and need to be further investigate. In this review, we provide insight into the TME of HNCs, classifying and summarizing EVs derived from different cell types and illuminating their complex signaling networks involved in mediating tumor proliferation, invasion and metastasis, vascular angiogenesis and cancer drug resistance. In addition, we highlight the application of EVs in HNCs, underlining the special pathological and physiological environment of HNCs. The application of tumor heterogeneous EVs in saliva and circulating blood diagnostics will provide a new perspective for the early screening, real-time monitoring and prognostic risk assessment of HNCs. Given the concept of precise and individual therapy, nanostructured EVs are equipped with superior characteristics of biocompatibility, low immunogenicity, loadability and modification ability, making these molecules one of the new strategies for HNCs treatment.
SUCCESSFULLY PREDICTING RECURRENCE OF COLORECTAL POLYPS AT RESECTION- A UK TERTIARY REFERRAL CENTRE EXPERIENCE
Authors: E Hossain, S Thayalasekaran, A Alkandari, S Arndtz, M Abdelrahim, P Bhandari, L Varytimiadis
Journal: Endoscopy (2019)

To identify colorectal polyp features during a complex EMR which could be associated with its recurrence.
Wake up call for collegiate athlete sleep: narrative review and consensus recommendations from the NCAA Interassociation Task Force on Sleep and Wellness
Authors: Emily Kroshus, Jessica Wagner, David Wyrick, Amy Athey, Lydia Bell, Holly J Benjamin, Michael A Grandner, Christopher E Kline, Jessica M Mohler, J Roxanne Prichard, Nathaniel F Watson, Brian Hainline
Journal: British Journal of Sports Medicine (2019)

Sleep is an important determinant of collegiate athlete health, well-being and performance. However, collegiate athlete social and physical environments are often not conducive to obtaining restorative sleep. Traditionally, sleep has not been a primary focus of collegiate athletic training and is neglected due to competing academic, athletic and social demands. Collegiate athletics departments are well positioned to facilitate better sleep culture for their athletes. Recognising the lack of evidence-based or consensus-based guidelines for sleep management and restorative sleep for collegiate athletes, the National Collegiate Athletic Association hosted a sleep summit in 2017. Members of the Interassociation Task Force on Sleep and Wellness reviewed current data related to collegiate athlete sleep and aimed to develop consensus recommendations on sleep management and restorative sleep using the Delphi method. In this paper, we provide a narrative review of four topics central to collegiate athlete sleep: (1) sleep patterns and disorders among collegiate athletes; (2) sleep and optimal functioning among athletes; (3) screening, tracking and assessment of athlete sleep; and (4) interventions to improve sleep. We also present five consensus recommendations for colleges to improve their athletes’ sleep.
Preventive bilateral mastectomy (PBS) in BRCA mutation carriers with ovarian cancer: Is it justified?
Authors: T. Safra, B. Waissengrin, D. Gerber, R. Bernstein-Molcho, R. Shaizaf, J. Taff, F. Mugia, M. Frey
Journal: Annals of Oncology (2019)

Background: To determine the incidence of breast cancer (BC) in BRCA mutation carriers (BRCA+) after ovarian cancer (OC) diagnosis, and to re-evaluate BC surveillance in BRCA+ with OC. Methods: A consecutive chart review, from 2000 to 2017, of OC patients at three medical centers: one in the USA and two in Israel. Clinical data collected included demographics, BRCA mutation types, timing of BC diagnosis (before or after OC diagnosis) and family history of cancer. Results: Analysis revealed 284 BRCA+ with a median age at diagnosis of 55 years (range, 31.3-90) and median follow-up of 59.5 months (6-92); 209 patients were BRCA1 (73.5%) and 75 were BRCA2 (26.5%). The most common mutation was 185delAG (30.7%). Thirty-six patients (12.7%) were diagnosed with BC before OC. Fifty-four patients (20.5%) had a family history of BC and 187 (65%) were Ashkenazi Jews. Only 11 patients (3.89%) developed BC after OC diagnosis. Median time to BC after OC diagnosis was 109 months (29-93). There was a non-significant increase in BC after OC, and in BC prior to OC diagnosis, but there was no correlation of BC with family history. Conclusions: The incidence of BC after OC diagnosis in the BRCA+ population was lower than expected. This finding may be attributed the high rate of OC mortality prior to BC development, OC chemotherapy treatment, or BC and OC clustering in families. Prophylactic bilateral mastectomy and/or MRI breast surveillance should be re-evaluated in this population and is possibly needed only in long survivors. Further investigation is warranted. Legal entity responsible for the study: Local IRB. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.