tbuckley/cabot-search huggingface dataset:
When can active surveillance be less active? Prediction of long-term nonreclassification for men with low-risk prostate cancer.
Authors: Matthew R. Cooperberg, Anna V Faino, Lisa F Newcomb, Peter Carroll, James T Kearns, James D. Brooks, Michael Fabrizio, Martin Gleave, Todd Matthew Morgan, Atreya Dash, Peter Nelson, Ian Murchie Thompson, Andrew Wagner, Daniel W. Lin, Yingye Zheng
Journal: Journal of Clinical Oncology (2018)

140 Background: Active surveillance is endorsed as the preferred management strategy for most men with low-risk prostate cancer. However, nearly all active surveillance protocols entail prostate specific antigen (PSA) testing every 3-6 months, and prostate biopsies every 1-2 years. For many men with indolent tumors, this regimen is overly intense, and exposes men to the discomfort, risks, and costs of repeated biopsies. We aimed to determine if some men can be safely selected for a less intense surveillance regimen by predicting the probability of non-reclassification over the next 4 years of surveillance. Methods: Data were collected from men in the multicenter Canary Prostate Active Surveillance Study (PASS), in which PSAs are collected q3 months and biopsies performed 12 months of diagnosis and then every 2 years. For inclusion in this study, men had to have undergone ≤ 1 follow up biopsy, and have Gleason grade group 1 at diagnosis. Reclassification was defined as increase in Gleason grade group on subsequent biopsy; those without reclassification were censored at last study contact, treatment or 2 years after last biopsy. A dynamic risk prediction model based on a Cox regression with robust variance estimates was used to construct and test a model predicting non-reclassification. Results: Of 1082 men included, 362 (33%) reclassified and the remaining were censored. The final regression model included percent of biopsy cores involved, prior biopsy history, time since diagnosis, BMI, prostate size, diagnostic PSA, and PSAk (a measure of PSA kinetics). This dynamic risk prediction model was assessed at a measurement time of 1 year after diagnosis, predicting risk of reclassification at 4 years. Men at lowest and highest deciles of this model-based risk faced 6% (95%CI 0-12%) and 73% (55-84%) risks of reclassification within 5 years. For at least 10% of the men in the cohort, the negative predictive value (NPV) for reclassification was 95% or higher. Conclusions: A substantial proportion of men with low-risk prostate cancer can safely be followed with a de-intensified active surveillance protocol, which would improve both the tolerability and cost-effectiveness of this management strategy.
Phase 1 study of glutaminase (GLS) inhibitor CB-839 combined with either everolimus (E) or cabozantinib (Cabo) in patients (pts) with clear cell (cc) and papillary (pap) metastatic renal cell cancer (mRCC).
Authors: Nizar M. Tannir, Alice C. Fan, Richard J. Lee, Bradley Curtis Carthon, Othon Iliopoulos, James Walter Mier, Manish R. Patel, Funda Meric-Bernstam, Angela DeMichele, Martin Henner Voss, James J. Harding, Ramaprasad Srinivasan, Geoffrey Shapiro, Melinda L. Telli, Pamela N. Munster, Richard D. Carvajal, Yonchu Jenkins, Samuel H. Whiting, Johanna C. Bendell, Todd Michael Bauer
Journal: Journal of Clinical Oncology (2018)

603 Background: CB-839 is a first-in-class inhibitor of GLS that targets tumor glutamine utilization, a pathway upregulated in kidney cancer. CB-839 combines with E or Cabo in pre-clinical RCC models to inhibit metabolic pathways resulting in enhanced anti-tumor activity. The CX-839-001 study includes cohorts evaluating the safety, efficacy and recommended Phase 2 dose (RP2D) of CB-839 in combination with E (CBE) or Cabo (CB-Cabo) in pts with mRCC. Here we report results from the CBE and CB-Cabo cohorts. Methods: Eligibility criteria included mRCC with cc or pap histology, ECOG 0-1, RECIST measurable disease and, for cc pts, treatment with at least 1 prior anti-VEGF therapy. Pts received escalating doses of CB-839 (PO BID) in a 3+3 design, either 400-800 mg with E (10 mg PO QD) or 600-800 mg with Cabo (60 mg PO QD). Tumor response (RECIST 1.1) was assessed every 8 wks. Results: 27 pts (22 cc, 3 pap, 2 other) were enrolled in CB-E escalation (n = 17) and expansion (n = 10) cohorts (7 at 400 mg, 13 at 600 mg, 7 at 800 mg) and 11 pts (9 cc, 2 pap) in CB-Cabo escalation cohorts (6 at 600 mg, 5 at 800 mg). Median prior lines of therapy was 2 for CBE (including 64% of cc pts with ≥2 prior anti-VEGF therapies) and 3 for CB-Cabo (range 0-6). A maximum tolerated dose was not reached; 800 mg was selected as the RP2D for CB-839. The most common treatment-related Gr≥3 AEs were fatigue (11%), anemia, hyperglycemia, and neutropenia (7% each) for CBE (N = 27) and diarrhea (14%) and platelet count decreased (14% including 1 DLT at 600 mg) for CB-Cabo (N = 7). Of 24 evaluable CBE pts there was 1 PR and 21 SD for a disease control rate (DCR = CR + PR + SD) of 92% with a median PFS of 7.1 mo (95% CI 4 - 11). For 9 evaluable CB-Cabo pts the ORR and DCR were 44% (4 PR) and 100%, respectively. Conclusions: The tumor metabolism inhibitor CB-839 combines with full dose of RCC targeted therapies, E and Cabo, with good tolerability and encouraging clinical activity in heavily-pretreated mRCC pts. CB-Cabo ORR and DCR of 44% and 100% are promising, and CBE DCR of 92% and PFS of 7.1 mo compare favorably to historical E monotherapy. Randomized Phase 2 studies have been initiated (CBE) or are planned (CB-Cabo). Clinical trial information: NCT02071862.
Post marketing surveillance study of cabazitaxel (CBZ) in Japanese patients with castration resistant prostate cancer (CRPC) in real world settings.
Authors: Hideyasu Matsuyama, Nobuaki Matsubara, Tomoyuki Taguchi, Takeshi Seto, Kazuhiro Suzuki
Journal: Journal of Clinical Oncology (2018)

290 Background: The study evaluated safety and efficacy of CBZ in Japanese patients (pts) with CRPC in real world settings. Methods: This prospective, observational study targeted all CRPC pts receiving CBZ in daily practice between September 2014 and June 2015. Observation period was 1 year after first dose of CBZ given. Adverse drug reactions (ADRs) were evaluated for safety by CTCAE 4.0. Overall survival (OS), time to treatment failure (TTF) and prostate specific antigen (PSA) response rate (≥30% PSA decrease) were the efficacy endpoints. Two groups, those given 25mg/m 2 of CBZ as initial dose (C25) and those given 20mg/m 2 of CBZ (C20), were comparatively analyzed. This study was supported by Sanofi. Results: Of 662 enrolled pts with CRPC treated with CBZ, 660 pts were analyzed. ADRs occurred in 511 pts (77.4%). Most frequent all grade ADRs were neutropenia (49.2%), febrile neutropenia (18.0%) and anemia (14.2%). Median OS and TTF were 319 and 116 days, respectively. Of 540 PSA evaluable pts, 158 (29.3%) achieved PSA response. Populations for post hoc analysis were 159 pts for C25 and 190 pts for C20. Patient characteristics were similar C25 and C20 groups. Statistical significant differences were observed between C25 and C20 groups for OS (Hazzard Ratio [HR] = 0.71) and TTF (HR = 0.78) in favor of C25 group. Initial dose of CBZ remained as the independent prognostic factor for OS and TTF in univariate and multivariate analysis. There was no significant difference for PSA response rate. ≥ Grade 3 ADRs with C25 and C20 occurred in 129 pts (81.1%) and 116 pts (61.1%), respectively. Conclusions: Safety profile of CBZ was generally consistent with clinical studies conducted before approval in Japan. Although there are some limitations of studies done in real world settings, there were significant differences for OS and TTF between C25 and C20. Less ADRs occurred with C20. [Table: see text]
Type 1 Diabetes in Parents and Risk of Attention Deficit/Hyperactivity Disorder in Offspring: A Population-Based Study in Sweden
Authors: Jianguang Ji, Tianhui Chen, Jan Sundquist, Kristina Sundquist
Journal: Diabetes Care (2018)

OBJECTIVE To explore whether a family history of type 1 diabetes (T1D) is associated with an increased incidence of attention deficit/hyperactivity disorder (ADHD) in offspring. RESEARCH DESIGN AND METHODS Individuals with T1D were identified from the nationwide Swedish National Hospital Discharge Register and Swedish Outpatient Register in Sweden and were linked to the Swedish Multi-Generation Register to identify their offspring. Cox regression was used to calculate the hazard ratio (HR) of ADHD in offspring of patients with T1D compared with the general population. RESULTS A total of 15,615 individuals were born after their parents were diagnosed with T1D. After a set of confounding factors was controlled for, offspring of T1D patients had a significantly increased risk of ADHD with an HR of 1.29 (95% CI 1.15–1.42). Maternal T1D was associated with an enhanced risk of ADHD (HR 1.35 [95% CI 1.18–1.55]) compared with paternal T1D (HR 1.20 [95% CI 1.03–1.41]), but the difference was not statistically significant. CONCLUSIONS In this retrospective cohort study, we found that a parental history of T1D was associated with a 29% increased risk of being diagnosed with ADHD. However, the underlying mechanisms need to be explored in future studies.
GMC clarifies position on disabled trainees and medical students unable to perform CPR
Authors: Abi Rimmer
Journal: BMJ (2013)

The General Medical Council has issued a statement clarifying that disabled trainees and medical students are not required to carry out cardiopulmonary resuscitation if they are unable to do so.1

The regulator issued the statement after it was told by the Medical Schools Council that there are currently around 10 disabled students who are expected to graduate from medical school but who might have difficulties at later stages of their training. These included, the statement said, “a wheelchair user who is able to direct but not perform CPR.” The statement said that …
Serum-based biomarkers and liver metastases in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Patrick Cotogno, Lahiru Ranasinghe, Elisa Ledet, Brian E. Lewis, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2018)

372 Background: Metastatic castrate-resistant prostate cancer patients with liver metastases have a poor prognosis. No large studies to date have investigated the clinical and biochemical parameters associated with liver metastases in this population. Methods: Patient data was obtained from 1,281 men with mCRPC that were enrolled on to three phase III clinical trials for the treatment of their disease. This clinical trial data was obtained from Project Data Sphere (www.projectdatasphere.org), an initiative of the CEO Roundtable on Cancer's Life Sciences Consortium. Multiple logistic regression was performed on clinical and biochemical baseline variables to test their association with the presence of liver metastases on baseline CT/MRI imaging. Variables assessed included prior docetaxel exposure, ECOG performance status, albumin, alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), hemoglobin, lactate dehydrogenase (LDH), prostate specific antigen (PSA), and total bilirubin. The investigation included lab variables when treated as both dichotomous (based on normal-abnormal ranges) and continuous. Results: Multiple variable analysis demonstrated that an abnormally elevated serum AST and/or LDH was associated with an increased likelihood of having documented radiographic liver metastases (p &lt; 0.0001). The predicted probability of having liver metastases for an abnormally elevated AST or LDH was 13.90% (95% CI 9.12 – 20.59) and 16.80% (95% CI 13.19 – 21.16), respectively. Patients with both an elevated AST and LDH had a 31.31% (95% CI 24.0 – 39.73) probability of having liver metastases as compared to only 6.67% (95% CI 5.17 – 8.57) for those with normal values. The ROC curve for the final model (AST + LDH) containing dichotomous predictors was 0.6683 (p &lt; 0.0001), which was not significantly different when treating the predictors as continuous (p = 0.4858). Conclusions: Our analysis demonstrated a significant association between the presence of liver metastases and elevated serum levels of AST and LDH. More research is needed to validate these biomarkers and determine their application in the clinical setting.
Postgraduate diploma in aesthetic surgery
Authors: Abhilash Jain, Adel Fattah
Journal: BMJ (2009)

Aesthetic surgery forms an important part of the curriculum for training in plastic surgery; however, exposure to patients with cosmetic problems is limited in the NHS. Traditionally, training in cosmetic surgery has been obtained by doing fellowships near the end of training, which commonly last for three months. The Royal College of Surgeons has also started specialised courses in aesthetic surgery, including cadaveric dissection. To deal with the problem of limited training in aesthetic surgery the University of London has established a diploma course in aesthetic surgery to provide a core curriculum for surgeons. It targets established surgeons and surgical or medical trainees and leads to a postgraduate degree from the University of London—PGDipAesSurg. Qualification requirements for the course are MB BS and part 2 membership of the Royal College of Surgeons (MRCS) or equivalent.

The course is a two year, part time, web based distance learning programme starting in October. It consists of structured distance e-learning, DVD or …
Integrative whole exome, transcriptome, and clinical profiling of biliary tract cancers (BTCs).
Authors: Nguyen H. Tran, Pankaj Vats, Dan R. Robinson, Mark Zalupski, Katherine E Hersberger, Mishal Mendiratta-Lala, Chandan Kumar-Sinha, Yi-Mi Wu, Robert J Lonigro, Xuhong Cao, Arul Chinnaiyan, Vaibhav Sahai
Journal: Journal of Clinical Oncology (2018)

279 Background: BTC is clinically and genomically heterogeneous and next generation sequencing may identify disease subsets with distinct prognostic and therapeutic implications. Methods: Patients (pts) with BTC underwent whole exome and transcriptome sequencing via the Michigan Oncology Sequencing (MI-ONCOSEQ) platform between 09/2011 and 07/2017. Results: 53 pts (47.2% female) with median age 60 (range 17-72) years had 38 intrahepatic, 6 perihilar, and 4 extrahepatic distal cholangiocarcinoma (CCA) while 3 had gallbladder and 2 mixed CCA/hepatocellular carcinoma. Forty-one pts (77.3%) had advanced BTC at diagnosis and 40 (75.5%) received platinum doublet as first line therapy. The most frequent somatic mutations were TP53 (35.8%), BAP1 (18.9%), KRAS (17.0%), IDH1 (15.1%), PBRM1 (13.2%), ARID1A (11.3%), and SMAD4 (11.3%). Median overall survival (OS) in 8 pts with IDH1 mutation was 16.8 months (none received IDH1 inhibitor). Putative pathogenic germline variants were noted in 6 (11.3%) pts of which 4 were biallelic (MSH2, BRCA1, BRCA2 and MUTYH) and 2 monoallelic (ATM and FH). Germline mutation in FH has not been reported in BTC. Biallelic DNA damage repair pathway mutations were noted in 14 (26.4%; 11 somatic, 3 germline) pts and their median OS was 16.8 months. Of these 9 pts with advanced BTC received 1 st line platinum therapy and had a median PFS of 9.3 months (4 PR, 3 SD). Nine (17%) pts had FGFR2 fusion (6 partners); median OS not yet reached (6 alive; 5 received FGFR inhibitor). Potentially targetable molecular alterations (IDH1, MSH2, BRCA1/2, PALB2, ATM, FGFR2, ERBB2) were identified in 27 (50.9%) pts. Copy number profile shows frequent loss of chr1p, chr3p, chr4, chr6q, chr8p, chr9, and gain of chr1q, chr7, and chr8q. Immune profiling &amp; pathway analysis of BTCs with clinical correlation is ongoing. Conclusions: Integrative sequencing of BTCs with clinical profiling will lead to more precise treatment of pts with BTCs.
Editor’s Choice: Draining costs
Authors: Tom Moberly
Journal: BMJ (2015)

The rising cost of doctors’ indemnity cover is now threatening the viability of some health services, doctors warn in BMJ Careers this week (http://bit.ly/1OeQ4fO). Anne Gulland looks at the sharp rise in indemnity fees and hears how these costs might affect the ability of GPs to continue to provide out of hours care to their patients. In addition, a recent news story reports …
Elastomeric sensor surfaces for high-throughput single-cell force cytometry
Authors: Ivan Pushkarsky, Peter Tseng, Dylan Black, Bryan France, Lyndon Warfe, Cynthia J. Koziol-White, William F. Jester, Ryan K. Trinh, Jonathan Lin, Philip O. Scumpia, Sherie L. Morrison, Reynold A. Panettieri, Robert Damoiseaux, Dino Di Carlo
Journal: Nature Biomedical Engineering (2018)
THE IMPACT OF CIRCULATING GALECTIN-3 LEVELS ON LONG-TERM OUTCOMES AFTER MYOCARDIAL INFARCTION IN THE COMMUNITY
Authors: Rabea Asleh, Maurice Enriquez-Sarano, Allan Jaffe, Sheila Manemann, Susan Weston, Ruoxiang Jiang, Veronique Roger
Journal: Journal of the American College of Cardiology (2018)
Impact of chronic hepatitis virus infection on the feasibility and efficacy for Asian patients with hepatocellular carcinoma in phase I clinical trials
Authors: T. Koyama, S. Kondo, T. Shimizu, Y. Fujiwara, S. Kitano, T. Ebata, A. Shimomura, C. Morizane, T. Okusaka, N. Yamamoto
Journal: Annals of Oncology (2018)
A multimodal infection control and patient safety intervention to reduce surgical site infections in Africa: a multicentre, before–after, cohort study
Authors: Benedetta Allegranzi, Alexander M Aiken, Nejla Zeynep Kubilay, Peter Nthumba, Jack Barasa, Gabriel Okumu, Robert Mugarura, Alexander Elobu, Josephat Jombwe, Mayaba Maimbo, Joseph Musowoya, Angèle Gayet-Ageron, Sean M Berenholtz
Journal: The Lancet Infectious Diseases (2018)
Thromboembolic events after high-intensity training during cisplatin-based chemotherapy for testicular cancer.
Authors: Lene Thorsen, Sophie D. Fossa, Hege Sagstuen Haugnes, Torgrim Tandstad, Marianne Brydoy, Torbjorn Wisloff, Elisabeth Edvardsen, Gunhild Maria Gjerset, Karl-Otto Larsen, Per Morten Sandset, Carola Henriksson, Helene FS Negaard
Journal: Journal of Clinical Oncology (2017)

4551 Background: Physical activity (PA) is believed to reduce acute side-effects as deconditioning, fatigue and nausea during chemotherapy and enhance post-treatment physical and psychosocial recovery. The national multicenter randomized TAST-trial (clinicaltrial.gov: NCT02577172) aimed to determine the effect of high-intensity training (HIT) during chemotherapy for testicular cancer (TC) on acute and post-treatment physical- and psychosocial outcomes. Methods: Patients aged 18 – 60 years with newly diagnosed metastatic TC, planned for 3 or 4 cisplatin-based chemotherapy cycles in combination with etoposide (EP) or etoposide plus bleomycin (BEP), were randomized to HIT during 9 or 12 weeks of chemotherapy or to one lifestyle counseling session (LCS) during first cycle. The HIT included two supervised endurance interval sessions per week, of which 10-15 minutes per session at 85 – 95 % of peak heart rate. The intensity, duration and number of the intervals were predetermined, but adjusted in accordance to the patients’ daily condition. Thromboembolic (TE) complications were registered consecutively. Results: Among the first 9 patients randomized to HIT, 33% (3 patients aged 22, 30 and 44 years) developed severe TE complications; 2 cases of pulmonary embolism (respectively at day 9 and 7 of BEP cycle 2) and 1 myocardial infarction (at day 7 of BEP cycle 3). Common for these patients were non-seminoma TC, clinical stage IIA, good prognosis group and no known risk factors for TE events. TE complications were not observed among the 10 patients randomized to the LCS. Conclusions: Since TC patients within good prognosis group are expected to have about 5 % risk of TE complications during or shortly after cisplatin-based chemotherapy, we cannot exclude that the HIT may have contributed to the unexpected high number of TE events. Until possible mechanisms explaining our observations have been explored, we discourage high-intensity endurance training during cisplatin-based chemotherapy for TC. These observations led to closure of the TAST-trial after inclusion of 19 of 94 planned patients. Clinical trial information: NCT02577172.
QUANTITATIVE MODELING OF LV INFLOW CHARACTERIZES IMPAIRED LEFT VENTRICULAR FUNCTION, ATRIAL FUNCTION AND LV-LA COUPLING
Authors: Julio A. Chirinos, Swetha Gaddam, Zeba Hashmath, Anila Hussain, Bilal Ansari, Jonathan Lee, Yueya Ge, Jessica Kim, Rachana Miller, Rushik Bhuva, Scott Akers
Journal: Journal of the American College of Cardiology (2018)
Medical profession must change to remove gender disparity across specialties, says Academy of Medical Royal Colleges
Authors: Caroline White
Journal: BMJ (2014)

The UK medical profession as a whole needs to look at its “structures, culture, and behaviours” to remove gender disparity across medical specialties, the Academy of Medical Royal Colleges has said.1

The academy raised the issue in response to a Daily Mail article by the surgeon J Meirion Thomas, which argued that women “avoid the more demanding specialities” and that the feminisation of medicine was harming the health service.2

In the article Thomas cited General Medical Council figures that indicated a shift in the gender balance of UK doctors in favour of women by 2017, describing them as “a worrying trend.”3 He said this shift would have “profound implications for the way the NHS works,” and he argued that “gender imbalance is already having a negative effect on …
MSc in Surgical Science (UCL)
Authors: Claire Middleton
Journal: BMJ (2006)

Senior house officers with membership of the Royal College of Surgeons (MRCS) who want to benefit from a structured research programme. It's popular among those hoping to do orthopaedics, plastic surgery, or general surgery. It is a full time 12 month taught programme consisting of a series of lectures for about two months, followed by laboratory based research for the remaining time.

Most candidates do the course after completing their basic surgical rotation and MRCS and before applying for a specialist registrar post.

To get experience of doing original research without having to worry about funding and grants. As it is for one year it is intensive, but the advantage is that you are out of mainstream surgery for only a year.

The course starts in …
Surgeons urge NHS England to ban minimum waits
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The Royal College of Surgeons has urged NHS England to stop clinical commissioning groups imposing minimum waiting times that result in some patients waiting at least three months to see a specialist.

A freedom of information request sent by the college found several examples of CCGs that had imposed minimum waiting times for non-urgent surgery in an effort to save money. These included South West Lincolnshire CCG, which has contractual agreements with three hospitals in its area stating that patients cannot receive routine elective care before 12 weeks. …
Treatment approaches and outcomes in plasmacytomas: analysis using a national dataset
Authors: Gaurav Goyal, Adam C. Bartley, Shealeigh Funni, Jonathan Inselman, Nilay D. Shah, Ariela L. Marshall, Aneel A. Ashrani, Prashant Kapoor, Urshila Durani, Shahrukh K. Hashmi, Mustaqeem A. Siddiqui, Francis K. Buadi, Ronald S. Go, Robert A. Kyle, Shaji Kumar, Wilson I. Gonsalves
Journal: Leukemia (2018)
INCREASED OXIDIZED LIPOPROTEINS ASSOCIATE WITH NON-CALCIFIED CORONARY PLAQUE IN PSORIASIS
Authors: Alexander Sorokin, Kazuhiko Kotani, Amit Dey, Charlotte Harrington, Joseph Lerman, Jonathan Chung, Justin Rodante, David A. Bluemke, Marcus Chen, Martin Playford, Nehal Mehta
Journal: Journal of the American College of Cardiology (2018)
Facing change: developing resilience for staff, associate specialist, and specialty doctors
Authors: Catherine Tregoning, Shirley Remington, Steven Agius
Journal: BMJ (2014)

There is growing recognition of the importance of resilience for doctors and their careers. <b>Catherine Tregoning</b>,<b> Shirley Remington</b>,<b> and Steven Agius </b>describe an initiative to introduce resilience workshops for SAS doctors