tbuckley/cabot-search huggingface dataset:
Abstract P6-15-03: Outcome after neoadjuvant chemotherapy in elderly breast cancer patients – a pooled analysis of individual patient data from eight prospectively randomized controlled trials
Authors: G von Waldenfels, S Loibl, J Furlanetto, M Anna, B Lederer, C Denkert, C Hanusch, J Huober, C Jackisch, S Kümmel, G von Minckwitz, A Schneeweiss, M Untch, K Rhiem, PA Fasching, JU Blohmer
Journal: Cancer Research (2018)

Abstract Introduction: Recent studies showed the high and independent impact of age (&amp;lt;40 years) on pathologic complete remission (pCR) and prognosis for patients undergoing neoadjuvant chemotherapy (NACT). Some physicians might not consider elderly patients (&amp;gt;65 years) for NACT due to poor prognosis or higher toxicity. The aim of this analysis is to help selecting appropriately elderly women who would benefit from NACT. Secondly, survival parameters will be investigated in several clinical and histological subgroups. Methods: From 1998 to 2010, eight prospectively randomized German Breast Group (GBG) trials of anthracycline- and taxane-based NACT were performed and analyzed in this study. Results: Compared to the overall average, women older than 65 years had significant larger tumors and more overall lymph node involvement. Also, compared to patients younger than 51 years, they had more lobular invasive tumors. Histologically, they had more G2 tumors, more estrogen-receptor positive tumors. PCR (ypT0 ypN0) was strongly associated with age: &amp;gt;65y: 11.7%; 51-65y: 14.1%; 40-50y: 17.3%; &amp;lt;40y: 20.9%. The multivariable logistic regression analysis of clinical parameters showed that young age, clinical stage T4, invasive ductal cancer and poor differentiated breast cancer are predictive for high pCR. The multivariate analyses of molecular subgroups also showed that age &amp;gt;65years is a predictor of significant (p&amp;lt;0.05) lower pCR in TNBC and HR positive/HER2- breast cancers. Nonetheless, in this cohort, HER2+ patients showed pCR rates as high - and for HR+/HER2+ even higher - pCR rates compared to younger patients. Discussion: This study underlines the unfavorable impact of higher age on pCR, but it shows nevertheless a realistic chance for pCR if NACT is applied - especially for HER2+ patients. Furthermore, elderly patients in this analysis with non-TNBC have a good prognosis (comparable to younger patients) regarding OS, even if they do not have pCR. Citation Format: von Waldenfels G, Loibl S, Furlanetto J, Anna M, Lederer B, Denkert C, Hanusch C, Huober J, Jackisch C, Kümmel S, von Minckwitz G, Schneeweiss A, Untch M, Rhiem K, Fasching PA, Blohmer JU. Outcome after neoadjuvant chemotherapy in elderly breast cancer patients – a pooled analysis of individual patient data from eight prospectively randomized controlled trials [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-03.
Barriers to influenza vaccination in healthcare workers
Authors: Miguel Pereira, Siân Williams, Louise Restrick, Paul Cullinan, Nicholas S Hopkinson
Journal: BMJ (2018)

Annual influenza vaccination is recommended for healthcare workers to reduce risk to themselves, their patients, and their families.12 Discussing mandatory vaccination, McCartney mentions our recent study,34 which found that a 10% rise in vaccination rate was associated with a 10% fall in sickness absence, which she said “may reflect better organised trusts being …
Functional Outcome After Intracranial Pressure Monitoring
Authors: Eberval Gadelha Figueiredo, Leonardo Christiaan Welling, Manoel Jacobsen Teixeira
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
I am a psychology student applying for a graduate course in medicine this September. What type of work experience would be appropriate before I start a medical course?
Authors: Howard Clark
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Lipidomic Profiling Links the Fanconi Anemia Pathway to Glycosphingolipid Metabolism in Head and Neck Cancer Cells
Authors: Xueheng Zhao, Marion G. Brusadelli, Sharon Sauter, Melinda Butsch Kovacic, Wujuan Zhang, Lindsey E. Romick-Rosendale, Paul F. Lambert, Kenneth D.R. Setchell, Susanne I. Wells
Journal: Clinical Cancer Research (2018)

Purpose: Mutations in Fanconi anemia (FA) genes are common in sporadic squamous cell carcinoma of the head and neck (HNSCC), and we have previously demonstrated that FA pathway depletion in HNSCC cell lines stimulates invasion. The goal of our studies was to use a systems approach in order to define FA pathway-dependent lipid metabolism and to extract lipid-based signatures and effectors of invasion in FA-deficient cells.Experimental Design: We subjected FA-isogenic HNSCC keratinocyte cell lines to untargeted and targeted lipidomics analyses to discover novel biomarkers and candidate therapeutic targets in FA-deficient cells. Cellular invasion assays were carried out in the presence and absence of N-butyldeoxynojirimycin (NB-DNJ), a biosynthetic inhibitor of the newly identified class of gangliosides, to investigate the requirement of ganglioside upregulation in FA-deficient HNSCC cells.Results: The most notable element of the lipid profiling results was a consistent elevation of glycosphingolipids, and particularly the accumulation of gangliosides. Conversely, repression of this same class of lipids was observed upon genetic correction of FA patient-derived HNSCC cells. Functional studies demonstrate that ganglioside upregulation is required for HNSCC cell invasion driven by FA pathway loss. The motility of nontransformed keratinocytes in response to FA loss displayed a similar dependence, thus supporting early and late roles for the FA pathway in controlling keratinocyte invasion through lipid regulation.Conclusions: Elevation of glycosphingolipids including the ganglioside GM3 in response to FA loss stimulates invasive characteristics of immortalized and transformed keratinocytes. An inhibitor of glycosphingolipid biosynthesis NB-DNJ attenuates invasive characteristics of FA-deficient HNSCC cells. Clin Cancer Res; 24(11); 2700-9. ©2018 AACR.
Efficacy of Larotrectinib in<i>TRK</i>Fusion–Positive Cancers in Adults and Children
Authors: Alexander Drilon, Theodore W. Laetsch, Shivaani Kummar, Steven G. DuBois, Ulrik N. Lassen, George D. Demetri, Michael Nathenson, Robert C. Doebele, Anna F. Farago, Alberto S. Pappo, Brian Turpin, Afshin Dowlati, Marcia S. Brose, Leo Mascarenhas, Noah Federman, Jordan Berlin, Wafik S. El-Deiry, Christina Baik, John Deeken, Valentina Boni, Ramamoorthy Nagasubramanian, Matthew Taylor, Erin R. Rudzinski, Funda Meric-Bernstam, Davendra P.S. Sohal, Patrick C. Ma, Luis E. Raez, Jaclyn F. Hechtman, Ryma Benayed, Marc Ladanyi, Brian B. Tuch, Kevin Ebata, Scott Cruickshank, Nora C. Ku, Michael C. Cox, Douglas S. Hawkins, David S. Hong, David M. Hyman
Journal: New England Journal of Medicine (2018)

Fusions involving one of three tropomyosin receptor kinases (TRK) occur in diverse cancers in children and adults. We evaluated the efficacy and safety of larotrectinib, a highly selective TRK inhibitor, in adults and children who had tumors with these fusions.We enrolled patients with consecutively and prospectively identified TRK fusion-positive cancers, detected by molecular profiling as routinely performed at each site, into one of three protocols: a phase 1 study involving adults, a phase 1-2 study involving children, or a phase 2 study involving adolescents and adults. The primary end point for the combined analysis was the overall response rate according to independent review. Secondary end points included duration of response, progression-free survival, and safety.A total of 55 patients, ranging in age from 4 months to 76 years, were enrolled and treated. Patients had 17 unique TRK fusion-positive tumor types. The overall response rate was 75% (95% confidence interval [CI], 61 to 85) according to independent review and 80% (95% CI, 67 to 90) according to investigator assessment. At 1 year, 71% of the responses were ongoing and 55% of the patients remained progression-free. The median duration of response and progression-free survival had not been reached. At a median follow-up of 9.4 months, 86% of the patients with a response (38 of 44 patients) were continuing treatment or had undergone surgery that was intended to be curative. Adverse events were predominantly of grade 1, and no adverse event of grade 3 or 4 that was considered by the investigators to be related to larotrectinib occurred in more than 5% of patients. No patient discontinued larotrectinib owing to drug-related adverse events.Larotrectinib had marked and durable antitumor activity in patients with TRK fusion-positive cancer, regardless of the age of the patient or of the tumor type. (Funded by Loxo Oncology and others; ClinicalTrials.gov numbers, NCT02122913 , NCT02637687 , and NCT02576431 .).
Design and Endpoints for Clinical Trials in Primary Sclerosing Cholangitis
Authors: Cyriel Y. Ponsioen, Keith D. Lindor, Ruby Mehta, Lara Dimick‐Santos
Journal: Hepatology (2018)

Primary sclerosing cholangitis (PSC) is a rare and chronic liver disease for which there is no effective therapy. Interest has grown in developing treatments for this condition, with several agents proposed as potential therapies. However, there is a lack of clarity about how to measure clinical benefit in trials involving patients with this complex and rare disease. This article reviews regulatory information, the available literature on natural history, as well as potential candidate clinical and surrogate endpoints for PSC. (H epatology 2018; 00:000‐000).
Training review will introduce more specialist GPs in Scotland
Authors: Abi Rimmer
Journal: BMJ (2015)

The Shape of Training review will allow more specialist general practitioner roles to be created in Scotland, the chair of the review’s steering group has said.

Ian Finlay, chair of the UK Shape of Training Steering group, speaking at a conference on professionalism and excellence in Edinburgh last month, said that more extended, specialist GP roles would be created as a …
I completed the vocational training scheme last year and I am about to apply for partnership in my training practice. What points am I expected to raise in my application letter?
Authors: Rodger Charlton
Journal: BMJ (2007)

Have a career related problem that needs answering? Can9t find the person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site <b>www.bmjcareers.com/advicezone</b>
A dose-escalation study of docetaxel, oxaliplatin and S-1 (DOS) as a first-line therapy for patients with unresectable metastatic gastric cancer.
Authors: Yasushi Sato, Tamotsu Sagawa, Yasuo Takahashi, Hiroyuki Ohnuma, Kyoko Hamaguchi, Masahiro Hirakawa, Koshi Fujikawa, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Tetsuji Takayama
Journal: Journal of Clinical Oncology (2018)

174 Background: Although the triplet regimen of docetaxel/cisplatin/S-1 (DCS) has shown promising activity and conversion rate in patients with unresectable metastatic gastric cancer (UMGC) in Japan, it was accompanied by severe adverse events. Recent studies suggested that oxaliplatin was almost as active, and relatively less toxic, than cisplatin in combination regimens for UMGC and can therefore replace cisplatin. The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), recommended dose (RD), and preliminary efficacy of docetaxel/oxaliplatin/S-1 (DOS) instead of DCS in patients with UMGC. Methods: Previously untreated 16 patients with histologically proven UMGC were enrolled. Docetaxel and oxaliplatin were administered intravenously on day 8. S-1 was administered orally twice a day on days 1-14. Each cycle was repeated every 3 weeks. DLTs were evaluated during the first cycle of treatment. Three dose-escalations of DOS were used in this study namely, level 1 (50/100/80 mg/m 2 ), level 2 (50/130/80 mg/m 2 ), and level 3 (60/130/80 mg/m 2 ). Results: Among the six patients, one patient each experienced DLTs (febrile neutropenia and diarrhea) at level 1 and 2 doses, respectively. While two more patients experienced DLTs (febrile neutropenia and diarrhea) after administration of level 3 doses. Therefore, two additional patients were enrolled into the study at level 2. However, both these patients subsequently exhibited DLTs (febrile neutropenia and diarrhea). Therefore, we concluded that the MTD and RD with this regimen were level 2 and level 1, respectively, and that the DLT were grade 3 diarrhea and febrile neutropenia. The overall response rate was 78% (7/9) of the patients with measurable lesions, consisting of two complete response and five partial responses. Five patients underwent conversion surgery. Conclusions: The RD of the 3-weekly DOS regimen in patients with UMGC was docetaxel at 50 mg/m 2 and oxaliplatin at 100 mg/m 2 on day 8 and S-1 at 80 mg/m 2 on days 1-14. The efficacy and ease of administration make the regimen a promising alternative to DCS. A phase II study using this RD regimen is currently underway. Clinical trial information: 000015849.
Abstract P4-04-01: Loss of mismatch repair predicts resistance to endocrine therapy and sensitivity to CDK4/6 inhibitors in ER+ breast cancer
Authors: S Haricharan, N Punturi, P Singh, KR Holloway, M Anurag, J Schmelz, C Schmidt, JT Lei, V Suman, K Hunt, JA Olson, J Hoog, S Li, S Huang, DP Edwards, SM Kavuri, MN Bainbridge, CX Ma, MJ Ellis
Journal: Cancer Research (2018)

Abstract Estrogen receptor positive (ER+) breast cancer is treated with endocrine therapy but intrinsic resistance occurs in ˜1/3 of patients and acquired resistance in ˜1/5 of the remainder. While many resistance mechanisms have been explored, clinical trials testing associated therapeutics have had mixed outcomes. Understanding mechanisms of resistance and finding therapeutic strategies to target them, therefore, remain important challenges. In this study we discover an intriguing link between mismatch repair (MMR) deficiency, specifically of the MutL complex (MLH1/3, PMS1/2), and endocrine therapy resistance in ER+ disease. We find a direct role for MutL loss in inducing endocrine therapy resistance in vitro and in vivo by knocking down multiple MutL genes using CRISPR and stable shRNA approaches validated using standard rescue experiments. We identify the underlying mechanism: MutL deficiency in ER+ breast cancer abrogates Chk2-mediated feedback inhibition of CDK4/6 that appears necessary for endocrine therapy responsiveness. Consequently, pharmacological targeting of CDK4/6 in vitro and in vivo significantly inhibits growth of endocrine therapy resistant MutL-deficient ER+ breast cancer cells. These results are corroborated by data from a neoadjuvant clinical trial demonstrating that cell cycle regulation of MutL-mutant tumors is estrogen-independent but CDK4/6 dependent. The results of this study provide important biological and clinically relevant insights. 1) a novel role for MMR in endocrine therapy resistance 2) A mechanism underlying the effectiveness of CDK4/6 inhibitors in some de novo endocrine therapy resistant tumors. While there are currently no biomarkers to guide the use of CDK4/6 inhibitors for ER+ breast cancer, markers of MMR dysregulation could identify patients in whom CDK4/6 inhibition may, most effectively, prevent disease recurrence. Citation Format: Haricharan S, Punturi N, Singh P, Holloway KR, Anurag M, Schmelz J, Schmidt C, Lei JT, Suman V, Hunt K, Olson Jr JA, Hoog J, Li S, Huang S, Edwards DP, Kavuri SM, Bainbridge MN, Ma CX, Ellis MJ. Loss of mismatch repair predicts resistance to endocrine therapy and sensitivity to CDK4/6 inhibitors in ER+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-04-01.
Prevalence and Types of Genital Lesions in Organ Transplant Recipients
Authors: Kumar S. Nadhan, Mary Larijani, James Abbott, Alden M. Doyle, Anthony W. Linfante, Christina Lee Chung
Journal: JAMA Dermatology (2018)

Squamous cell carcinoma (SCC) is the most common skin cancer diagnosed in solid organ transplant recipients (OTRs) and confers significant mortality. The development of SCC in the genital region is elevated in nonwhite OTRs. Viral induction, specifically human papillomavirus (HPV), is hypothesized to play a role in the pathophysiology of these lesions.To assess the prevalence and types of genital lesions observed in OTRs.This retrospective review included 496 OTRs who underwent full skin examination from November 1, 2011, to April 28, 2017, at an academic referral center. The review was divided into 2 distinct periods before a change in clinical management that took effect on February 1, 2016 (era 1) and after that change (era 2). Patient awareness of genital lesions was assessed. All lesions clinically suggestive of malignant tumors were biopsied and underwent HPV polymerase chain reaction typing.Number and types of genital lesions, proportion of malignant tumors positive for HPV, and patients cognizant of genital lesions.Of the total 496 OTRs, 376 OTRs were evaluated during era 1 (mean [SD] age, 60 years; age range, 32-94 years; 45 [65.2%] male; 164 [43.6%] white) and 120 OTRs were evaluated during era 2 of the study (mean age, 56 years; age range, 22-79 years; 76 [63.3%] male; 30 [25.0%] white). Overall, 111 of the 120 OTRs (92.5%) denied the presence of genital lesions during the history-taking portion of the medical examination. Genital lesions were found in 53 OTRs (44.2%), cutaneous malignant tumors (basal cell carcinoma and SCC in situ) in 6 (5.0%), genital SCC in situ in 3 (4.2%), and condyloma in 29 (24.2%). Eight of the 12 SCC in situ lesions (66.7%) were positive for high-risk HPV. Seven tested positive for HPV-16 and HPV-18, and 1 tested positive for high-risk HPV DNA but could not be further specified.Genital lesions in OTRs are common, but awareness is low. All OTRs should undergo thorough inspection of genital skin as a part of routine posttransplant skin examinations. Patients with darker skin types are disproportionately affected by cutaneous genital malignant tumors and should undergo a targeted program of early detection, prevention, and awareness focused on the risk of genital skin cancer after transplant. High-risk HPV subtypes are associated with genital SCC in OTRs. Additional studies are warranted to identify significant risk factors for HPV infection and to assess the utility of pretransplant HPV vaccination in the prevention of cutaneous genital malignant tumors.
Validation of a genomic classifier to predict adverse pathology in men diagnosed with low risk prostate cancer.
Authors: Hyung Lae Kim, Ping Li, Huei-Chung Huang, Samineh Deheshi, Beatrice Knudsen, Hatem Abou-Ouf, Lucia L.C. Lam, Jennifer Margrave, Marguerite Du Plessis, Elai Davicioni, Jeffrey J. Tosoian, Ashley Ross, John W. Davis, M. Eric Hyndman, Eric A. Klein, Tarek A. Bismar
Journal: Journal of Clinical Oncology (2018)

71 Background: The Decipher 22-feature genomic classifier (GC) has been validated to predict metastasis and prostate cancer specific mortality in needle biopsy (Bx) tissue of men with intermediate and high-risk prostate cancer. We validate GC in diagnostic Bx specimens for the prediction of high-grade/stage (HGS) disease at radical prostatectomy (RP) in men with low and favorable-intermediate (fav-int) NCCN risk group disease. Methods: We identified 176 men diagnosed with low or fav-int NCCN risk group disease who had available Bx GC scores and pathological information after RP from Cedars-Sinai, University of Calgary, Cleveland Clinic, MD Anderson, and Johns Hopkins. The GC score was calculated based on a locked random forest model. Scores range from 0-1 with cut points for GC low, intermediate and high risk groups as &lt;0.45, 0.45-0.6, and &gt;0.6, respectively. The primary endpoint was HGS (Gleason group 3-5 or pT3b or lymph node invasion (LNI)). Univariable (UVA) and multivariable (MVA) logistic regression models were used to evaluate GC and CAPRA. Results: Median age of the cohort was 62 years, 87% and 13% had Bx grade group (GG) 1 or 2 disease. 76% and 24% were NCCN low and fav-int risk, respectively. CAPRA classified 70% as low (0-2) and 30% as average risk (3-5). GC classified 80% low, 16% intermediate and 4% high genomic risk. After RP, 41% had RP GG 1, 46% GG 2 and 13% had GG 3-5 disease. pT3b or positive lymph nodes were observed in 7 men (4%), overall 27 (15%) of men had HGS at RP. In the UVA and MVA, GC was the only significant predictor of HGS with odds ratio (OR) of 1.38 and 1.34 per 10% unit increase, before and after adjusting for CAPRA (p=0.011, 0.027). A low risk score (GC&lt;0.45) had a negative predictive value (NPV) of 92% to identify men who do not have HGS at RP. In exploratory analysis, a very low risk cut-point (GC&lt;0.2) was found which had a sensitivity of 96% and an NPV of 99%. 26% of men had GC&lt;0.2. Conclusions: We validated GC in a multi-institutional study to predict HGS at RP among men with NCCN low and fav-int risk disease with high sensitivity and NPV. Future studies will aim to validate the very low risk genomic cut-point to guide decision-making and follow-up biopsy protocols for men considering or in active surveillance.