tbuckley/cabot-search huggingface dataset:
Outcomes in bone predominant (BP) urothelial carcinoma (UC).
Authors: Ariel Ann Nelson, Aman Opneja, Behtash Ghazi Nezami, Pingfu Fu, Scott Dawsey, Matthew David Wright, Cheryl Eitman, Simon P. Kim, Matthew M. Cooney, Petros Grivas, Gregory MacLennan, Christopher J. Hoimes
Journal: Journal of Clinical Oncology (2018)

441 Background: The clinical phenotype of BP UC includes those patients (pts) with at least as many or more bone lesions than non-bone lesions. UC molecular subtypes that may correlate with prognosis have been defined. Better understanding of the clinical BP phenotype, which might correspond to the p53-like molecular subtype, is needed. Methods: We searched our biorepository to identify pts with metastatic UC. Electronic records of identified pts were reviewed and those with accessible records who received treatment at our institution were selected. Demographic, pathologic, treatment, response, progression-free and overall survival (PFS, OS) data were recorded. Imaging was reviewed to identify non-bone predominant (NBP) or BP disease based on imaging criteria. Results: 23 NBP and 9 BP pts, (59% men) were identified. Of BP pts, 44% had bone metastatic disease present at diagnosis (dx) vs. none of the NBP. Only 8% of NBP pts developed bone metastases during their course. The median number of lines of therapy in the metastatic setting was 2 for each cohort. All BP pts received platinum therapy vs. 74% of NBP. 11% of BP pts were treated with checkpoint immunotherapy (CPI) vs. 34% of NBP. 70% of BP pts received palliative radiation (all to bone) vs. 4% of the NBP cohort. The median OS from date of UC dx was 27.5 months. There was a significant difference in OS between BP and NBP cohorts from UC dx date (16.9 vs. 30.6 months, p &lt; 0.0001) as well as from muscle invasive bladder cancer (MIBC) dx date (15.2 vs. 22.8 months, p = 0.019), respectively. OS from initiation of 1 st line treatment in the metastatic setting for the entire cohort was 12.5 months and was not significantly different between the cohorts (p = 0.633). PFS from dx of MIBC to date of 1st progression or death was not significant (p = 0.08) with median PFS of 8.4 vs. 13.6 months for BP vs. NBP cohorts, respectively. Conclusions: BP pts require more frequent palliative radiation and have shorter OS measured from time of dx, but not significantly different when measured from the initiation of 1 st line treatment, compared to NBP pts. Further analysis with a larger cohort is ongoing for validation. Molecular analysis on pathological specimens is planned.
REMO (Resuscitation and Emergency Management Onfield)
Authors: David Warriner
Journal: BMJ (2008)

The course is for anyone whose life support skills are rusty. Specifically it is aimed at health professionals involved in the acute care of adult athletes. I was the most junior member in attendance; the others were a mixture of sports doctors, general practitioners (civilian and military), junior doctors, and physiotherapists. Topics covered include airway management, basic and advanced life support, use of an automated external defibrillator, spinal immobilisation, and orthopaedic emergencies. Other acute medical topics such as the management of burns, anaphylaxis, hyperthermia and hypothermia, drowning, and soft tissue injuries are also dealt with.

I did the two day weekend course as a core trainee 1 at the start of my core medical training. It is held twice a year in May and September in Stoke on Trent.

Despite having worked in accident and emergency, I have little experience …
US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments
Authors: Suparna B. Wedam, Julia A. Beaver, Laleh Amiri-Kordestani, Erik Bloomquist, Shenghui Tang, Kirsten B. Goldberg, Rajeshwari Sridhara, Amna Ibrahim, Geoffrey Kim, Paul Kluetz, Amy McKee, Richard Pazdur
Journal: Journal of Clinical Oncology (2018)

Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5% (range: 4% to 26%), dependent on subtype. Investigator-assessed progression-free survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBM PFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.
Evaluation of the Roche LightMix Gastro parasites multiplex PCR assay detecting Giardia duodenalis, Entamoeba histolytica, cryptosporidia, Dientamoeba fragilis, and Blastocystis hominis
Authors: J. Friesen, J. Fuhrmann, H. Kietzmann, E. Tannich, M. Müller, R. Ignatius
Journal: Clinical Microbiology and Infection (2018)
Diet affects gut microbiota and modulates hospitalization risk differentially in an international cirrhosis cohort
Authors: Jasmohan S. Bajaj, Ramazan Idilman, Leila Mabudian, Matthew Hood, Andrew Fagan, Dilara Turan, Melanie B. White, Fatih Karakaya, Jessica Wang, Rengül Atalay, Phillip B. Hylemon, Edith A. Gavis, Robert Brown, Leroy R. Thacker, Chathur Acharya, Douglas M. Heuman, Masoumeh Sikaroodi, Patrick M. Gillevet
Journal: Hepatology (2018)

The relative ranking of cirrhosis-related deaths differs between high-/middle-income countries. Gut microbiome is affected in cirrhosis and is related to diet. Our aim was to determine the effect of differing dietary habits on gut microbiota and clinical outcomes. Outpatient compensated/decompensated patients with cirrhosis and controls from Turkey and the United States underwent dietary and stool microbiota analysis. Patients with cirrhosis were followed till 90-day hospitalizations. Shannon diversity and multivariable determinants (Cox and binary logistic) of microbial diversity and hospitalizations were studied within/between groups. Two hundred ninety-six subjects (157 U.S.: 48 controls, 59 compensated, 50 decompensated; 139 Turkey: 46 controls, 50 compensated, 43 decompensated) were included. Patients with cirrhosis between cohorts had similar Model for End-Stage Liver Disease (MELD) scores. American patients with cirrhosis had more men, greater rifaximin/lactulose use, and higher hepatitis C/alcohol etiologies. Coffee intake was higher in Americans whereas tea, fermented milk, and chocolate intake were higher in Turkey. The entire Turkish cohort had a significantly higher microbial diversity than Americans, which did not change between their controls and patients with cirrhosis. In contrast, microbial diversity changed in the U.S.-based cohort and was the lowest in decompensated patients. Coffee, tea, vegetable, chocolate, and fermented milk intake predicted a higher diversity whereas MELD score, lactulose use, and carbonated beverage use predicted a lower microbial diversity. The Turkish cohort had a lower risk of 90-day hospitalizations. On Cox and binary logistic regression, microbial diversity was protective against 90-day hospitalizations, along with coffee/tea, vegetable, and cereal intake.In this study of patients with cirrhosis and healthy controls from the United States and Turkey, a diet rich in fermented milk, vegetables, cereals, coffee, and tea is associated with a higher microbial diversity. Microbial diversity was associated with an independently lower risk of 90-day hospitalizations. (Hepatology 2018;68:234-247).
Making it in British Medicine—essential guidance for international doctors
Authors: Rais Irfan Ahmed
Journal: BMJ (2005)

T his book starts with basic information for somebody just starting to think about a medical career in the United Kingdom and it contains valuable information about exams, visa issues, and career prospects. There are fruitful instructions for doctors who are struggling to secure their entry into the NHS, including tips on organising their CVs, finding a clinical attachment, applying for jobs, and doing interviews.

The discussion about career progression in different specialties will be of great interest to doctors who are in training posts or working on …
“First, do no harm” is true for NHS management too
Authors: Ted A Willis
Journal: BMJ (2018)

McCartney is spot on in her column about the reasons for the current NHS crisis.1 Huge amounts of money been wasted on initiatives like the internal market, the white elephant Darzi centres, and the ultimate in futility that is the Care Quality Commission. But much worse is that these and other unproved and time consuming ideas (like the Quality and …
I would like to know your opinion on the demand for cosmetic (aesthetic) medicine in the United Kingdom at the moment, and in the future?
Authors: Abhilash Jain
Journal: BMJ (2005)

<b>www.bmjcareers.com/advicezone</b> 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.
Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-Cell Targets in Human IDH-Mutant Glioma
Authors: Steffen Dettling, Slava Stamova, Rolf Warta, Martina Schnölzer, Carmen Rapp, Anchana Rathinasamy, David Reuss, Kolja Pocha, Saskia Roesch, Christine Jungk, Uwe Warnken, Volker Eckstein, Niels Grabe, Christoph Schramm, Markus A. Weigand, Andreas von Deimling, Andreas Unterberg, Philipp Beckhove, Christel Herold-Mende
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Successful immunotherapies for IDHmut gliomas require better knowledge of T-cell target antigens. Here, we elucidated their antigen repertoire recognized by spontaneous T-cell responses using an unbiased proteomic approach. Experimental Design: Protein fractionations of tissue lysates from IDHmut gliomas (n = 4) were performed. Fractions were tested by IFNγ ELISpot assay for recognition through patients' T cells. Proteins of immunogenic fractions were identified by mass spectrometry and validated by in silico-predicted synthetic long peptides in patients of origin, additional IDHmut glioma patients (n = 16), and healthy donors (n = 13). mRNA and protein expression of immunogenic antigens was analyzed in tumor tissues and IDHmut glioma stem-like cells (GSC). HLA-A*02–restricted T-cell epitopes were functionally determined by short peptides and numbers of antigen-specific T cells by HLA-peptide tetramer analysis. Results: A total of 2,897 proteins were identified in immunogenic tumor fractions. Based on a thorough filter process, 79 proteins were selected as potential T-cell antigens. Twenty-six of these were recognized by the patients’ T cells, and five of them (CRKII, CFL1, CNTN1, NME2, and TKT) in up to 56% unrelated IDHmut glioma patients. Most immunogenic tumor-associated antigens (TAA) were expressed in IDHmut gliomas and GSCs, while being almost absent in normal brain tissues. Finally, we identified HLA-A*02–restricted epitopes for CRKII, NME2, and TKT that were recognized by up to 2.82% of antigen-specific peripheral cytotoxic T cells in IDHmut glioma patients. Conclusions: By analyzing the repertoire of T-cell target antigens in IDHmut glioma patients, we identified five novel immunogenic TAAs and confirmed their expression on IDHmut tumors and GSCs. Clin Cancer Res; 24(12); 2951–62. ©2018 AACR.
“Curious George Goes to the Hospital”: teaching toddlers how good healthcare works
Authors: Luca Bartolini
Journal: BMJ (2018)

I found Bell’s paper on Peppa Pig both amusing and deep.1 As the father of a 3 year old girl I’d like to discuss an episode of Curious George titled “Curious George Goes to the Hospital,” which is a positive example of how hospitals and diseases can be effectively explained to toddlers without resorting to magic or sugar coated scenarios. …
Hepatic-targeted RNA interference provides robust and persistent knockdown of alpha-1 antitrypsin levels in ZZ patients
Authors: Alice M. Turner, Jan Stolk, Robert Bals, Jason D. Lickliter, James Hamilton, Dawn R. Christianson, Bruce D. Given, Jonathan G. Burdon, Rohit Loomba, James K. Stoller, Jeffery H. Teckman
Journal: Journal of Hepatology (2018)
Informed Consent Training in Pediatrics—Are We Doing Enough?
Authors: Alan R. Tait, Raymond J. Hutchinson
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
68Ga-DOTATATE PET/CT Reveals Epstein-Barr Virus–Associated Nasopharyngeal Carcinoma in a Case of Suspected Sphenoid Wing Meningioma
Authors: Marcus Unterrainer, Cornelius Maihoefer, Clemens C. Cyran, Peter Bartenstein, Maximilian Niyazi, Nathalie Lisa Albert
Journal: Clinical Nuclear Medicine (2018)

Abstract In this case of suspected sphenoid wing meningioma, 68 Ga-DOTATATE PET/CT showed a somatostatin receptor (SSR)–expressing tumor with extension to the nasopharynx and SSR-expressing cervical lymph nodes. Subsequent biopsy from the nasopharynx revealed an Epstein-Barr virus (EBV)–associated, undifferentiated World Health Organization type 3 nasopharyngeal carcinoma (NPC), a potential clinical pitfall due to the reported high SSR expression of this tumor subtype. In consideration of the high target-to-background contrast, SSR ligands might be superior to 18 F-FDG for EBV-associated NPC PET imaging, particularly at the skull base. Somatostatin receptor ligands might furthermore offer interesting theranostic possibilities for patients with advanced/extensive EBV-associated NPC.
Editor’s Choice: Planning for patients
Authors: Tom Moberly
Journal: BMJ (2016)

The Royal College of Radiologists has presented a stark prediction that one in 10 consultant radiology posts will be vacant “for the foreseeable future” http://careers.bmj.com/careers/advice/Radiology\_services\_are\_%E2%80%9Con\_their\_knees%2C%E2%80%9D\_royal\_college\_warns.

The college argues that recruitment overseas and an expansion of training posts will be required to shore up the supply of radiologists that the UK needs. “Without that, the …
Repurposing ethacrynic acid for the treatment of bladder cancer.
Authors: Eugene Lee, Greg Reed, Prasad Dandawate, Gaurav Kaushik, Dharmalingam Subramaniam, Jeffrey M. Holzbeierlein, Shrikant Anant, Scott James Weir
Journal: Journal of Clinical Oncology (2018)

521 Background: Bladder cancer is a common cancer in the US. Approximately seventy-five percent of new cases present as non-muscle invasive bladder cancer (NMIBC) with a high recurrence rate. Our group has demonstrated in well-characterized human NMIBC cell lines that ethacrynic acid (EA) suppresses growth by inhibiting proliferation, clonogenicity, spheroid formation and inducing apoptosis. Additionally, EA affects markers of stemness and may work through the NOTCH signaling pathway. We present a clinical trial characterizing the safety and urinary tract exposure to EA and metabolites following oral administration in patients undergoing transurethral resection of bladder tumor (TURBT). Methods: Institutional review board approval (#3674) was obtained for a Pilot trial in patients with presumed non-muscle invasive bladder cancer undergoing TURBT. All participants were given a single, 50 mg oral dose of EA in the pre-operative bay. Urine was collected at baseline, upon insertion of cystoscope (30-60 minutes post dose), and post-operatively. Urine concentrations of EA and metabolites were determined using a fully-validated UPLC-MS/MS-based analytical method. Participants were monitored for adverse events. Results: Twelve participants participated in the trial between August 2016 and February 2017. Eleven male and one female patient (median age 70.5 years) were enrolled. Final pathology demonstrated urothelial carcinoma in 5/12 (42%) subjects, three with high grade T1 and two with low-grade Ta tumors. Urine concentrations of EA and conjugates observed 30-60 minutes post-dose were as follows: EA 0.1 ug/mL, EA-glutathione 0.2 ug/mL, EA-cysteine 3 ug/mL, and EA-mercapturate 2 ug/mL. No drug-related adverse events were observed following oral EA administration. Conclusions: Despite EA receiving FDA approval over 40 years ago, our pilot trial describes for the first time, urinary tract exposure of EA and its active metabolites in bladder cancer patients after a single oral dose. These data are guiding ongoing preclinical proof of principle studies evaluating EA alone and in combination with standard of care agents in bladder cancer models. These studies warrant further studies of EA in patients with non-muscle invasive bladder cancer. Clinical trial information: NCT02852564.
Increase in work intensity is unsustainable, say GPs
Authors: Abi Rimmer
Journal: BMJ (2015)

Delegates at the BMA’s conference of local medical committees in London on 21 May voted for a motion saying that the “increase in GP workload and increase in GP work intensity was unsustainable.”

The motion said that there was a disincentive to join the profession, “leading to an exodus of doctors away from the profession.” It called for urgent action to limit GPs’ workload …
Five novel loci associated with antipsychotic treatment response in patients with schizophrenia: a genome-wide association study
Authors: Hao Yu, Hao Yan, Lifang Wang, Jun Li, Liwen Tan, Wei Deng, Qi Chen, Guigang Yang, Fuquan Zhang, Tianlan Lu, Jianli Yang, Keqing Li, Luxian Lv, Qingrong Tan, Hongyan Zhang, Xiao Xiao, Ming Li, Xin Ma, Fude Yang, Lingjiang Li, Chuanyue Wang, Tao Li, Dai Zhang, Weihua Yue
Journal: The Lancet Psychiatry (2018)
A first-in-human phase I study of sEphB4-HSA (sEphB4) with expansion in hepatocellular (HCC) and cholangiocarcinoma (CCA).
Authors: Jacob Stephen Thomas, Heinz-Josef Lenz, Syma Iqbal, Denice D Tsao-Wei, Afsaneh Barzi, Vinay Duddalwar, Sarah Cole, Rabia Rehman, Xiomara Menendez, Valery Krasnoperov, Ren Liu, Qingru Feng, Parkash S. Gill, Anthony B. El-Khoueiry
Journal: Journal of Clinical Oncology (2018)

285 Background: EphrinB4, a receptor kinase, is associated with stage and survival in epithelial cancers. sEphB4 is a fusion protein of soluble EphB4 and albumin. sEphB4 binds to EphrinB2, a protein expressed in tumor cells and vessels, and blocks bidirectional signaling. sEphB4 downregulates the PI3K/AKT/mTOR pathway, inhibits angiogenesis, and promotes recruitment of cytotoxic T cells and NK cells. MTD was not reached during dose escalation. The RP2D was 10 mg/Kg weekly. Here we report the results of the expansion cohorts in HCC and CCA. Methods: The study evaluated the safety, PK, PD and efficacy of sEphB4 in pts with advanced solid tumors in a 3+3 design with expansion at the RP2D in 7 solid tumors including HCC and CCA. Pts received sEphB4 10 mg/kg IV weekly in 28-day cycles. Eligibility included ECOG 0-1, Child-Pugh score ≤ 7, platelets &gt; 50,000, AST/ALT ≤ 3xULN, serum bilirubin ≤ 1.5mg/dL and no uncontrolled hypertension. Results: 29 pts were treated: 17 HCC and 12 biliary cancers (8 CCA and 4 gallbladder). Median age was 63(25-77). ECOG PS was 1 in 76%. Median prior regimens were 1 (0-6) for HCC and 2 (1-3) for biliary cancers. 2 HCC pts had prior liver transplantation, 9 had prior anti PD-1 therapy and 2 had Child-Pugh score of B7. Median number of cycles was 4 (1-21) in HCC and 2 (1-17) in CCA. No grade 4 treatment-related adverse events (TRAE). Grade 3 TRAE were hypertension (41%) and fatigue, headache, neutropenia all in 1 pt each. Disease progression was the most common reason for treatment discontinuation. Median PFS in months was 5.0 (3.0-7.5) in HCC and 3.0 (1.6-9.2) in CCA. Median OS in months was 27.1 (4.4-27.1) in HCC and 12.0 (3.0-28.2) in CCA. Disease control rate was 70% in HCC and 42% in CCA including 1 PR in HCC. In HCC pts, 5/5 with 3+ EphrinB2 expression in tumor had PR or SD ≥ 6 months. Only 1/4 pts with ≤2+ expression had SD ≥ 4 months. 3/3 pts with HCC showed an increase in T cell infiltration, and decrease in pS6 (PI3K pathway activity) on post-treatment biopsy. Conclusions: sEphB4 has a manageable safety profile with preliminary evidence of anti-tumor activity in pretreated pts with HCC and biliary cancers. Several trials combining sEphB4-HSA with cytotoxic chemotherapy or immunotherapy are ongoing. Clinical trial information: NCT01642342.