tbuckley/cabot-search huggingface dataset:
Expanding the Scope of High-Value Practice Beyond Guideline-Based Care
Authors: Arjun Gupta, Kristin S. Alvarez, Deepak Agrawal
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
End use of terms “junior” and “trainee,” says Royal College president
Authors: Abi Rimmer
Journal: BMJ (2016)

The president of the Royal College of Surgeons of Edinburgh has called for the introduction of a new term to describe doctors in training rather than “junior” or “trainee” doctors.

In a letter to the health secretary, Jeremy Hunt, seen by BMJ Careers, Michael Lavelle-Jones wrote, “we ask that a less pejorative term be found …
Data sharing: making good on promises
Authors: Elizabeth Loder
Journal: BMJ (2018)

Nothing damages trust in medical research more than the idea that clinical trial data are being hidden or manipulated. Randomised controlled trials are widely considered the best way to evaluate treatment benefits, but trials are time consuming, expensive, and complex. It is thus vital to make full use of all information collected, and it seems evident that the public interest is served by independent scrutiny and replication of trial results. These things can happen only if trial data are shared.

In 2013 The BMJ became one of the first journals to require data sharing in clinical trials of drugs or devices (doi:10.1136/bmj.e7888). In 2015 we extended that policy to require data …
Outbreak of febrile gastroenteritis caused by Listeria monocytogenes 1/2a in sliced cold beef ham, Italy, May 2016
Authors: Cristiana Maurella, Silvia Gallina, Giuseppe Ru, Daniela Adriano, Alberto Bellio, Daniela Manila Bianchi, Laura Chiavacci, Maria Ines Crescio, Margherita Croce, Valeria D'Errico, Maria Franca Dupont, Alessandro Marra, Ubaldo Natangelo, Francesco Pomilio, Angelo Romano, Stefano Stanzione, Teresa Zaccaria, Fabio Zuccon, Maria Caramelli, Lucia Decastelli
Journal: Eurosurveillance (2018)

In May 2016, two separate clusters of febrile gastroenteritis caused by Listeria monocytogenes were detected by the local health authority in Piedmont, in northern Italy. We carried out epidemiological, microbiological and traceback investigations to identify the source. The people affected were students and staff members from two different schools in two different villages located in the Province of Turin; five of them were hospitalised. The epidemiological investigation identified a cooked beef ham served at the school canteens as the source of the food-borne outbreak. L. monocytogenes was isolated from the food, the stools of the hospitalised pupils and the environment of the factory producing the cooked beef ham. All isolates except one were serotype 1/2a, shared an indistinguishable PFGE pattern and were 100% identical by whole genome sequencing (WGS). By combining a classical epidemiological approach with both molecular subtyping and WGS techniques, we were able to identify and confirm a Listeria gastroenteritis outbreak associated with consumption of sliced cold beef ham.
Is it theoretically possible for a consultant to work exclusively in private practice?
Authors: Peter Mills
Journal: BMJ (2004)

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 (www.bmjcareers.com/advicezone) 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.
Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma: Exploratory pharmacogenomic analysis.
Authors: Daniel J. George, Jean-Francois Martini, Michael D. Staehler, Yen-Hwa Chang, Jan Breza, Jean-Jacques Patard, Robert J. Motzer, Ahmed Magheli, Giacomo Carteni, Frede Donskov, Bernard Escudier, Sherry Li, Michelle Casey, Olga Valota, Brigitte Laguerre, Allan J. Pantuck, Hardev S. Pandha, Anup Patel, Mariajose Lechuga, Alain Ravaud
Journal: Journal of Clinical Oncology (2018)

576 Background: In the phase III S-TRAC trial, adjuvant sunitinib (SU) prolonged disease-free survival (DFS) vs placebo (PBO) in patients with locoregional renal cell carcinoma at high risk of recurrence after nephrectomy (median 6.8 vs 5.6 y; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59–0.98; P= 0.03). An exploratory analysis evaluated associations between single nucleotide polymorphisms (SNPs) in angiogenesis-related genes and clinical outcomes in S-TRAC. Methods: Prospectively collected blood samples were genotyped for 10 SNPs and 1 insertion/deletion mutation with TaqMan assays. DFS was compared with a log-rank test for each SNP genotype in SU vs PBO arms and between SNP genotypes within each arm. P-values are unadjusted for multiplicity comparison. Results: Of 615 patients, 286 (142 SU; 144 PBO) were analyzed. There were generally no genotype frequency deviations from the Hardy-Weinberg equilibrium, but linkage disequilibrium was seen between VEGFA rs699947 and rs833061 on chromosome 6 (D′ = 1.000, r2 = 0.979). Longer DFS was observed with SU vs PBO for VEGFR1 rs9554320 C/C (median: not reached [NR] vs 5.56 y; HR 0.44, 95% CI 0.21–0.91; P= 0.023), VEGFR2 rs2071559 T/T (median: NR vs 4.47 y; HR 0.46, 95% CI 0.23–0.90; P= 0.020), and eNOS rs2070744 T/T (median: 7.07 vs 3.44 y; HR 0.53, 95% CI 0.30–0.94; P= 0.028), with a trend for VEGFR1 rs9582036 A/A (median: NR in both arms; P= 0.054) and SH3GL2 rs10963287 C/T (median: NR vs 5.35 y; P= 0.088). Shorter DFS was observed for VEGFR1 rs9582036 C/A vs C/C in the SU, PBO, and combined arms ( P&lt; 0.05); for A/A vs common, the association was only seen in the SU arm ( P= 0.022). VEGFR1 rs9554320 A/C was associated with shorter DFS vs A/A in the PBO ( P= 0.038) and combined arm ( P= 0.006), with a trend in the SU arm ( P= 0.051). VEGFR2 rs1870377 T/T was associated with longer DFS vs A/A in the combined arms, but not in the PBO arm (n = 7 with A/A genotype in the SU arm precluded statistical tests). Conclusions: Correlations between common VEGFR1 and VEGFR2 SNPs and longer DFS with SU suggest germline SNPs are predictive of improved outcomes with adjuvant SU. Due to the exploratory nature of this analysis, prospective validation studies are needed to confirm these findings. Clinical trial information: NCT00375674.
Prognostic value of serum interleukin-6 and YKL-40 and systemic inflammatory response in patients with unresectable pancreatic cancer.
Authors: Inna Chen, Christian Dehlendorff, Benny Vittrup Jensen, Per Pfeiffer, Jon K. Bjerregaard, Astrid Zedlitz Johansen, Svend Erik Nielsen, Fahimeh Andersen, Niels Henrik Hollander, Mette K. N. Yilmaz, Louise Skau Rasmussen, Julia S. Johansen
Journal: Journal of Clinical Oncology (2018)

267 Background: Interleukin-6 (IL-6) and YKL-40 (CHI3L1) are produced by pancreatic cancer (PC) cells and macrophages and activate inflammation. The aim of this prospective-retrospective biomarker study was to determine the prognostic value of serum IL-6 and YKL-40 and systemic inflammatory response in patients with PC receiving palliative chemotherapy. Methods: 625 patients with PC (M/F: 283/342; age &lt;70 vs. ≥70: 395/230; ECOG PS of 0/1/2/3: 214/315/92/4; stage 3 vs. 4: 129/496; treated with gemcitabine n=437, FOLFIRINOX n=117, gemcitabine and nab-Paclitaxel n=54 or other n=17) were included in the BIOPAC biomarker study from 5 hospitals in Denmark. Pretreatment serum values of IL-6 (R&amp;D Systems), YKL-40 (Quidel), and CA 19-9 (Siemens) were determined. Patients were grouped as low vs. high, dichotomized using cut-off for IL-6 &gt; 4.92 pg/ml, for CA19-9 &gt; 2183 U/ml and for YKL-40 &gt; 95% age-corrected percentile. The main outcome was overall survival (OS) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were computed using Cox proportional hazards regression. Results: 598 (95.7%) patients died during follow-up. In univariate analysis elevated IL-6 (HR 1.93, 95% CI 1.63-2.28) and elevated YKL-40 (HR 1.74, 95% CI 1.47-2.05) were associated with short OS. Similar results were found if IL-6 and YKL-40 were included as continuous log2-transformed variables. Multivariable analysis showed that elevated IL-6 (HR 1.61, 95% CI 1.33-1.94), elevated YKL-40 (HR 1.36, 95% CI 1.13-1.64), elevated CA19-9 (HR 1.30, 95% CI 1.09-1.56), higher PS (1 vs. 0; HR 1.46, 95% CI 1.21-1.77 and PS 2 vs. 0; HR 2.73, 95% CI 2.08-3.58) and stage 4 vs. 3 (HR 1.79, 95% CI 1.44-2.24) were independently associated with a poor OS. In a subgroup of 386 patients with available laboratory data, higher C-reactive protein (HR 1.20, 95% CI 1.13-1.26), white blood cells (HR 1.41, 1.17-1.71) and absolute neutrophils count (HR 1.35, 95% CI 1.15-1.59) log2-transformed and adjusted for age, sex, PS, CA 19-9 and stage were associated with short OS. Conclusions: Serum IL-6, YKL-40 and CA19-9 along with CRP, WBC and ANC are independent prognostic biomarkers in patients with unresectable PC.
Labour raises concern over public health, with a fifth of director posts vacant
Authors: Abi Rimmer
Journal: BMJ (2014)

Luciana Berger, Labour’s shadow minister for public health, has raised concern about public health provision after finding that 18% of director of public health posts in England are vacant. Berger asked the secretary of state for health how many local authorities currently employed acting or interim directors of public health and what steps were being taken to fill …
Endoscopic submucosal dissection for early esophageal cancer in elderly patients with relative indications for endoscopic treatment
Authors: Zhi-Peng Qi, Tao Chen, Bing Li, Zhong Ren, Li-Qing Yao, Qiang Shi, Shi-Lun Cai, Yun-Shi Zhong, Ping-Hong Zhou
Journal: Endoscopy (2018)

Abstract Background According to the Japanese Esophageal Society (JES) guidelines, early esophageal squamous cell carcinoma (SCC) involving the muscularis mucosae (M3) or upper submucosal (SM1) layers are relative indications for endoscopic submucosal dissection (ESD). Additional esophagectomy or chemoradiotherapy is recommended for patients with relative indications after evaluation. However, elderly patients (≥ 60 years) with relative indications in China often refuse additional treatment because of the debilitating side effects. The aim of this study was to evaluate the long-term outcomes of elderly patients with relative indications who did not undergo additional treatment after ESD. Methods Data from elderly patients with relative indications who underwent ESD for early esophageal SCC between January 2008 and December 2013 were reviewed retrospectively. Stricture and recurrence, and 5-year progression-free survival (PFS) and overall survival rates were compared with patients with absolute indications for ESD. Results 158 elderly patients were included and analyzed (89 in the absolute indications group and 69 in the relative indications group). The baseline characteristics were balanced between the two groups. During 56 months (range 1 – 108) of follow-up, the postoperative stricture rates were similar in the absolute and relative indications groups (21.3 % vs. 31.9 %; P = 0.13). The hazard ratio (HR) for PFS in the absolute vs. the relative indications groups was 1.025 (95 % confidence interval [CI] 0.36 – 2.95; P = 0.96). The 5-year PFS rates were 90.5 % (95 %CI 83.44 – 97.56) and 90.8 % (95 %CI 83.74 – 97.86) for the absolute and relative indications groups, respectively. The HR for overall survival in the absolute vs. the relative indications groups was 0.564 (95 %CI 0.13 – 2.52; P = 0.45). The 5-year overall survival rates were 96.6 % (95 %CI 92.88 – 100) and 95.6 % (95 %CI 90.70 – 100) for the absolute and relative indications groups, respectively. Conclusions Based on this study, regular follow-up without additional treatment may be considered as another choice for elderly patients with early esophageal SCC and relative indications after ESD.
Type III interferon-induced CBFβ inhibits HBV replication by hijacking HBx
Authors: Fengchao Xu, Hongxiao Song, Qingfei Xiao, Na Li, Hong Zhang, Genhong Cheng, Guangyun Tan
Journal: Cellular and Molecular Immunology (2018)

Hepatitis B virus (HBV) and its associated chronic infection remain serious health threats worldwide. However, there is still no impactful approach for clinical treatment of hepatitis B patients. Therefore, developing a better understanding of the interactions between HBV and its host is particularly important. HBV infection has been reported to induce type-III but not type-I or type-II interferon (IFN). In this study, we identified CBFβ, an HIV enhancer, as an HBV restriction factor that is specifically induced by type-III IFN in the early stages of HBV infection. Type-III IFN-induced IL-10 played an important role in the production of CBFβ. Interestingly, the interaction between CBFβ- and HBV-encoded regulatory protein X (HBx) enhanced the stability of CBFβ, but notably blocked HBx-mediated promotion of HBV replication. CBFβ expression was lower in HBV patients than in healthy persons, and the addition of serum from HBV patients inhibited CBFβ expression in HepG2 cells. On the contrary, HBV via HBsAg inhibited type-III IFN-induced CBFβ expression and decreased the anti-HBV activity of type-III IFN, suggesting that HBV inhibits antiviral interferon-stimulated gene (ISG) expression and induces IFN resistance. Collectively, our results demonstrate that type-III IFN-triggered and IL-10-induced CBFβ are crucial factors for inhibiting HBV replication, and the HBx–CBFβ–HBsAg axis reveals a new molecular mechanism of interaction between HBV and its hosts.
Effect of the leukocyte chemoattractant chemerin on PTEN via CMKLR1 in human prostate cancer.
Authors: Russell Kent Pachynski, Robert Crowder, William Shin, Keith Rennier
Journal: Journal of Clinical Oncology (2018)

282 Background: Recent data in preclinical models has shown that phosphatase and tensin homolog (PTEN) loss correlated with decreased tumor immune cell infiltration as well as decreased response to T cell-based immunotherapy. Chemerin ( RARRES2) is a recently identified endogenous leukocyte chemoattractant shown to recruit innate immune cells through its G-protein coupled receptor CMKLR1. RARRES2 is commonly downregulated in prostate and other cancers (eg sarcoma) compared to their normal tissue counterparts. Our previous preclinical studies showed that forced overexpression of chemerin in tumors was capable of recruiting immune effector cells into the tumor microenvironment and suppressing tumor growth. Methods: Here, we investigate the effects of chemerin on tumor cell intrinsic processes by exposing prostate and sarcoma tumor lines to exogenous recombinant chemerin in vitro. Evaluation of PTEN was performed at both the mRNA and protein levels, using both quantitative PCR as well as Western blotting. PTEN immunoprecipitation by and Malachite Green assays were used to determine PTEN activity. In vitro invasion assays were performed to investigate the functional impact of chemerin exposure on tumor intrinsic activity. Knockdown of CMKLR1 using siRNA was performed to determine its role in tumor response. Results: Using both prostate and sarcoma tumor lines, we found exogenous chemerin was able to significantly upregulate PTEN expression at both the mRNA and protein levels in a dose-dependent manner. PTEN phosphatase activity was also significantly increased by chemerin. Exposure to chemerin did not result in increased apoptosis or altered in vitro proliferation. Importantly, chemerin treatment significantly decreased in vitro tumor invasion. Knockdown of CMKLR1 resulted in loss of chemerin-induced PTEN and PTEN activity and restored tumor migration, suggesting a link between this GPCR and PTEN. Conclusions: For the first time to our knowledge, we have shown a link between chemerin and PTEN expression and activity in both prostate and sarcoma tumor lines. This work has potential clinical implications on both tumor cell intrinsic and extrinsic responses to chemerin-based immunotherapeutic strategies.
Genomic profiling of muscle invasive bladder cancer to predict response to bladder-sparing trimodality therapy.
Authors: David Tomoaki Miyamoto, Ewan Gibb, Kent William Mouw, Yang Liu, Chin-Lee Wu, Michael Drumm, Jonathan Lehrer, Hussam Al-Deen Ashab, Nicholas Erho, Marguerite Du Plessis, Kaye Ong, William U. Shipley, Elai Davicioni, Jason A. Efstathiou
Journal: Journal of Clinical Oncology (2018)

513 Background: Trimodality therapy with TURBT followed by chemoradiation is an acceptable alternative to cystectomy for muscle invasive bladder cancer (MIBC). Genomic profiling has demonstrated MIBC can be divided into molecular subtypes with differing responses to chemotherapy. We explored the utility of genomic data to select patients for bladder-sparing trimodality therapy. Methods: Transcriptome wide gene expression profiles were generated for 189 MIBC TURBT samples from patients treated with trimodality therapy at a single institution. Of these, 103 passed microarray QC. Molecular subtype and expression of bladder cancer genes were assessed for association with overall and disease-specific survival. Transcriptome wide differential expression analysis was used to explore gene set enrichment in trimodality therapy response groups. Results: The chemoradiation cohort (n = 103) had a median followup of 6.9 years for alive patients, and was classified into four subtypes: basal (n = 44), basal claudin-low (n = 12), infiltrated luminal (n = 17) and luminal tumors (n = 30). There was no significant difference in overall or disease-specific survival by subtype. However, higher expression of the luminal-associated PPARG was correlated with increased survival after adjusting for subtype and clinical factors (HR = 0.52, p = 0.002). In contrast, a p53 signature predicted worse survival after adjusting for clinical factors (HR = 1.92, p = 0.022). Elevated mRNA expression of the DNA damage repair gene MRE11 was associated with improved survival in the trimodality cohort (HR = 0.69, P = 0.031), consistent with its potential role as a predictive biomarker for radiation response. Gene set enrichment revealed differential regulation of immune pathways in trimodality therapy responders relative to non-responders, including enrichment of interferon gamma signaling (p = 0.01) and CXCL9 (p = 0.031), suggestive of an interplay between tumor immunologic microenvironment and response to chemoradiation. Conclusions: Transcriptional profiling of MIBC revealed gene signatures correlated with response to chemoradiation, suggesting the potential of genomics to guide use of trimodality therapy.
Peanut Allergy Prevention
Authors: Anna Volerman, Adam S. Cifu
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Loss of Toll-like receptor 2 results in accelerated leukemogenesis in the NUP98-HOXD13 mouse model of MDS
Authors: Darlene A. Monlish, Sima T. Bhatt, Eric J. Duncavage, Zev J. Greenberg, John L. Keller, Molly P. Romine, Wei Yang, Peter D. Aplan, Matthew J. Walter, Laura G. Schuettpelz
Journal: Blood (2018)
First Interim Analysis of the French National Observatory of Paroxysmal Nocturnal Hemoglobinuria Clones
Authors: Magali Le Garff-Tavernier, Bernard Drenou, Agathe Pruvot Debliquis, Remi Letestu, Bernard Chatelain, Thomas Boyer, Jean-Philippe Vial, Michael Peres, Véronique Harrivel, Gérard Socié, Regis Peffault De Latour, Orianne Wagner Ballon
Journal: Blood (2017)
GPs urge government to act on “unsustainable workload”
Authors: Abi Rimmer
Journal: BMJ (2014)

The “unsustainable workload” in general practice poses an “imminent risk to the safety of patients” and must be “urgently resolved” by the UK governments, GPs have said.

Delegates at the BMA’s conference of local medical committees (LMCs) in York voted unanimously in favour of a motion deploring the unsustainable workload in general practice. The motion warned of the “consequent collapse of services, the imminent risk to …