tbuckley/cabot-search huggingface dataset:
High neutrophil-to-lymphocyte ratio as an independent adverse prognostic factor in racial minorities with hepatocellular carcinoma.
Authors: Santiago Thibaud, Santiago Aparo, Jennifer W. Chuy, Andreas Kaubisch
Journal: Journal of Clinical Oncology (2018)

218 Background: An elevated neutrophil-to-lymphocyte ratio (NLR) has been shown to portend poor prognosis in various types of cancer, including hepatocellular carcinoma (HCC). However, studies that evaluated the prognostic significance of NLR did not include large numbers of Blacks and Hispanics. This single-center, retrospective study conducted on a large, racially diverse cohort explores the utility of NLR in predicting outcomes in minority populations. Methods: We identified patients (pts) diagnosed with HCC at our institution between the years 2000 and 2016. We calculated NLR at the time of diagnosis and divided pts into two groups: high NLR (NLR &gt; 3) and low NLR (NLR ≤3). Demographics, clinical characteristics, MELD/MELD-Na scores, ALBI scores and AFP levels were collected. Survival analysis was conducted using the Kaplan-Meier method. Cox proportional-hazards model was used for multivariate analysis. Results: 751 pts with HCC were included in this study. 542 (72%) were male. Median age was 61 years. 43% were Hispanic, 33% Black, 22% White and 2% Other. NLR was high in 246 pts (32.7%, mean 6.0 ± 3.8) and low in 505 pts (67.2%, mean 1.69 ± 0.7). Overall survival (OS) was significantly lower in the high NLR group (median survival 25.4 vs 49.6 months, HR 1.75, 95% CI 1.41-2.17, P &lt; 0.01). Subgroup analysis showed differences remained significant in the Hispanic group (n = 259, HR 1.93, 95% CI 1.30-2.86, P &lt; 0.01) and the Black group (n = 194, HR 1.99, 95% CI 1.28-3.09, P &lt; 0.01). The high NLR group had significantly higher MELD scores (mean 12.1 ± 5.0 vs 10.1 ± 3.8, P &lt; 0.01), MELD-Na scores (13.9 ± 5.6 vs 11.3 ± 4.4, P &lt; 0.01), ALBI scores (-2.05 ± 0.7 vs -2.28 ± 0.6, P &lt; 0.01) and AFP levels (median 28.9 vs 46.9, P = 0.02). An NLR &gt; 3 on multivariate analysis remained significantly associated with worse OS (HR 1.31; 95% CI 1.03-1.68; P = 0.02) after adjusting for age, gender, AFP and MELD-Na. Conclusions: NLR &gt; 3 at the time of diagnosis had a strong correlation with poor OS in a large, racially diverse cohort of pts with HCC. This correlation held true for both Hispanic and Black patients, who have been previously underrepresented in similar studies. Our findings support the utility of NLR as a prognostic tool in HCC.
BMA polls GPs on effects of 2013-14 contract changes
Authors: Helen Jaques
Journal: BMJ (2013)

The BMA is surveying its GP members on the effects of the general medical services (GMS) contract changes imposed on the profession in April.

The survey asks GPs in England how the 2013-14 contract has affected their workload, morale, practice income, and expenses. The survey also asks GPs for information about which directed enhanced services (DESs) GPs have chosen to offer and their level of engagement with their local clinical commissioning group (CCG). The results of the survey will be used to inform the next round of negotiations for the 2014-15 GMS …
Impact of lymph node ratio on survival in advanced head and neck cancer: National Cancer Data Base (NCDB).
Authors: Sukamal Saha, Mohammed Shaik, Gregory Johnston, Supriya Kumar Saha, Vikrom K. Dhar, Ujwala Koduru, Madan L. Arora, Lindsay Berbiglia, Jacob Burke, David Wiese
Journal: Journal of Clinical Oncology (2014)

6092 Background: Lymph node ratio (LNR), the no. of positive nodes divided by no. of nodes extracted, has prognostic importance in colon and breast cancer. We aim to evaluate the role of LNR in the treatment of head and neck cancer (HNC), as its prognostic value is unknown. Methods: Pts from NCDB with advanced HNC (1998-2010), including laryngeal (LC) and non laryngeal cancer (NLC), were analyzed. Pts underwent surgery of the primary site with neck dissection. Only pts with complete data of age, sex, grade, TNM staging, and LNR were included. Using the median LNR of 0.1, pts were divided into two groups: GpA (LNR <0.1) or GpB (LNR >0.1). 5yr overall survival (5yr OS) was compared using K-Meier. Multivariate analysis was performed using Cox-proportional model. An adjusted hazard ratio (aHR) was calculated for pts in both groups. Results: Of 81, 672 pts included, a majority were Stage III (16,562) or Stage IV (44,831) with 47,510 pts having nodal metastasis. Of these, 24,206 (51%) were in GpA and 23,304 (49%) in GpB. There were 4,564 LC pts in GpA and 4,059 in GpB. The median no. of +'ve LN were 2 and 4 while the median no. of LN extracted were 40 and 21, respectively. 5yr OS for GpA and GpB was 50% vs. 33% for Stage III and 40% vs. 24% for Stage IV. There were 19.462 NLC pts in GpA and 19,245 in GpB. The median no. of +'ve LN were 1 and 3 while the median no. of LN extracted were 36 and 17, respectively. 5yr OS for GpA and GpB was 60% vs. 57% for Stage III and 53% vs. 39% for Stage IV. The aHR of pts with LNR >0.1 compared to LNR <0.1 was 1.4 (95% CI 1.36-1.43), after adjusting for other prognostic covariates (Table 1). Conclusions: LNR has significant impact on the survival of pts with advanced HNC. LNR of 0.1 or higher in HNC is associated with 40% increased relative risk of death. Characteristics of patients in GpA (LNR < 0.1) and GpB (LNR > 0.1). Variables GpA(LNR<0.1) GpB(LNR>0.1) P-value No. of patients(%) 24,206(51%) 23,304(49%) Median age(yrs) 58 59 No. of LC(%) 4,564(53%) 4,059(47%) Median LN extracted 40 21 <0.001 Median positive LN 2 4 <0.001 5yr OS stage III 50% 33% <0.001 5yr OS stage IV 40% 24% <0.001 No. of NLC(%) 19,642(50.5%) 19,245(49.5%) Median LN extracted 36 17 <0.001 Median positive LN 1 3 <0.001 5yr OS stage III 60% 57% <0.001 5yr OS stage IV 53% 39% <0.001
Safety, effectiveness, and rapid adaptation of robotic gastrectomy for advanced gastric cancer.
Authors: Lin Chen, Jiyang Li, Hongqing Xi, Yunhe Gao, Jianxin Cui, Zhi Qiao, Kecheng Zhang, Tianyu Xie, Wenquan Liang, Bo Wei
Journal: Journal of Clinical Oncology (2018)

161 Background: As robotic surgery techniques advances, robotic gastrectomy has emerged as an alternative modality for advanced gastric cancer (AGC). However, there is a lack of supporting evidence regarding the safety, effectiveness and surgeon acceptance of robotic gastrectomy for AGC patients. Methods: An ambispective cohort study was conducted. We compared surgical and oncological outcomes between robotic and traditional laparoscopic gastrectomy for AGC patients. The Cumulative Sum (CUSUM) method was developed and used to analyze the learning curves of robotic gastrectomy for AGC by two surgeons who had different surgical experience. Results: From August 2011 to June 2017, a total of 134 AGC patients were performed robotic gastrectomy by surgeon A (n = 42) and surgeon B (n = 147). And there were 238 AGC patients received traditional laparoscopic gastrectomy which performed by the same two surgeons over the same period. There were no significant differences between the two operation methods regarding the clinicopathologic characteristics and long-term outcomes (p=0.737). However, robotic gastrectomy group had less operative blood loss (229 ml vs. 240 ml, p=0.031) and less Clavien-Dindo Grade II to IV complications (p=0.006) than laparoscopic group. Clinicopathologic characteristics, short-term and long-term outcomes of the patients treated by surgeon A and surgeon B are similarity. CUSUM analysis showed that operative time reached a stable state after around 12 cases in surgeon A who had more open gastrectomy experience than laparoscopic gastrectomy experience, and 21 cases in surgeon B who had more laparoscopic gastrectomy experience than open gastrectomy experience. The stable operation time was 242 min for surgeon A and 236 min for surgeon B. The number of lymph node dissections was 38 for surgeon A and 28 for surgeon B during their capacity-increasing phase. Conclusions: Robotic gastrectomy achieved superior short-term outcomes and comparable long-term outcomes compared with traditional laparoscopic gastrectomy for AGC patients. Surgeons with sufficient experience in either open or laparoscopic gastrectomy can rapidly overcome the learning curve and performed gastrectomy for AGC patients safely.
David Oliver: What’s wrong with being honest with the public about NHS pressures?
Authors: David Oliver
Journal: BMJ (2018)

In December I was on a conference panel discussing “How to save the NHS.” I said that we needed to be far more honest with the public and realistic about what the service can currently offer, given unprecedented demand, unfilled posts, and a widening gap in funding. We must make it clear to patients, I said, that they will often face longer waits in GP surgeries, emergency departments, and hospital clinics, and that they will be admitted to understaffed wards and often rushed out of hospital sooner than they might like, to free scarce beds for others.

The Daily Mail picked up on my comments, the subsequent headline screaming, “Top …
Accelerating Clinical Gene Editing
Authors: Bridget Kuehn
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
Safety and efficacy of axitinib (axi) in combination with pembrolizumab (pembro) in patients (pts) with advanced renal cell cancer (aRCC).
Authors: Michael B. Atkins, Elizabeth R. Plimack, Igor Puzanov, Mayer N. Fishman, David F. McDermott, Daniel C. Cho, Ulka N. Vaishampayan, Saby George, Thomas Olencki, Jamal Christo Tarazi, Brad Rosbrook, Kathrine C. Fernandez, Mariajose Lechuga, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2018)

579 Background: Prior studies combining programmed death-1 (PD-1) checkpoint inhibitors with tyrosine kinase inhibitors of the vascular endothelial growth factor (VEGF) pathway have been characterized by excess toxicity precluding further development. We hypothesized that a combination of axi, a more selective VEGF-pathway inhibitor, with pembro (anti-PD-1) would be well tolerated and yield antitumour activity in treatment-naïve pts with aRCC. Methods: This ongoing open-label phase Ib study of axi/pembro comprised a dose-finding phase to determine the maximum tolerated dose and dose expansion phase. Axi 5 mg was administered orally twice daily with pembro 2 mg/kg administered intravenously every 3 weeks. Tumors were assessed, using RECIST v1.1, at baseline, week 12, and every 6 weeks thereafter. The primary endpoint was dose-limiting toxicity (DLT) during the first 2 cycles (6 weeks), with secondary endpoints evaluating safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Between 23 Sept 2014 and 13 Oct 2015, 52 treatment-naïve pts with aRCC were enrolled. No unexpected toxicities were observed. Three DLTs were reported among the 11 pts treated in the dose-finding phase: transient ischemic attack (n = 1) and &lt; 75% of planned axi dosage administered due to treatment-related toxicity (n = 2). At cutoff date (March 30, 2017), 25 pts were receiving study treatment. Most common (≥10%) grade ≥3 all-causality AEs included hypertension (23%), diarrhoea (10%) and fatigue (10%). Most common ( &gt; 10%) potentially immune-related AEs included diarrhoea (29%), increased alanine aminotransferase (17%), or aspartate aminotransferase (13%), hypothyroidism (13%), and fatigue (12%). ORR was 73.1% (95% confidence intervals [CIs], 59.0–84.4). Median (95% CI) PFS was 20.9 (15.4–not evaluable) months. OS data were not mature at minimum follow-up period of 17.6 months, with 6 treatment-unrelated deaths reported. Conclusions: The combination axi/pembro is tolerable and exhibits promising antitumour activity in treatment-naïve pts with aRCC. A randomized phase 3 trial comparing the combination to sunitinib monotherapy is underway. Clinical trial information: NCT02133742.
The increasing mortality of idiopathic pulmonary fibrosis: fact or fallacy?
Authors: Christopher J. Ryerson, Martin Kolb
Journal: European Respiratory Journal (2018)

There is no debate that idiopathic pulmonary fibrosis (IPF) is a devastating disease that has a significant impact on patient morbidity and mortality. Patients with IPF experience symptoms throughout most of their disease, with disabling dyspnoea and cough that reduce quality of life. Most IPF patients eventually succumb to respiratory failure with a median survival of approximately 3 years from the time of diagnosis [1]. Two antifibrotic medications slow progression of IPF [2–5]; however, it has yet to be shown whether IPF mortality will change substantially with the availability of these therapies. There are likely multiple reasons that IPF-related mortality appears to be increasing in most European countries <http://ow.ly/Maty30gRrDl>
The role of whole pelvic nodal radiotherapy compared with prostate bed only radiotherapy after radical prostatectomy for prostate cancer.
Authors: Matthieu Caubet, David Pasquier, Aurelie Bertaut, Simon Grobois, Berardino De Bari, Francois Kleinclauss, Antoine Thiery Vuillemin, Etienne Martin, Magali Quivrin, Luc Cormier, Gilles Crehange
Journal: Journal of Clinical Oncology (2018)

93 Background: In international guidelines, target volumes for postoperative radiotherapy (PORT) after radical prostatectomy concern the bed of the prostate and seminal vesicles. The benefit of whole pelvic nodal radiotherapy (WPRT) in the case of PORT remains uncertain. Methods: We reviewed the charts of all patients diagnosed with high-risk prostate cancer after radical prostatectomy who were selected for PORT and treated with adjuvant radiotherapy (n = 242, 43.1%) or early salvage RT (n = 320, 56.9%) between 2002 and 2011. 111 patients (19.8%) who underwent WPRT were compared with 441 patients (80.2%) who had prostate bed radiotherapy only (PBRT). We examined associations between patient, tumor, and treatment characteristics and biochemical progression-free survival (bPFS), disease-free survival (DFS) and overall survival (OS) with uni- and multivariate analyses using Cox models. Acute and late toxicities were also compared between the two groups. Results: We found a significantly lower rate of acute G2+ gastrointestinal (GI) toxicity with PBRT than with WPRT with neither difference in acute G3+ nor on late GI toxicity. Regarding genitoruinary (GU) toxicity, we found no difference in acute G2+ or G3+ toxicity but rates of late G3+ GU toxicity were significantly lower in PBRT (1.55%) than in WPRT patients (p = 0.035). With a median follow-up of 65.2 months [95% CI: 62.8 - 67.9], a deleterious effect of WPRT was observed on OS (HR = 3.27 [95% CI: 1.44 - 7.45], p = 0.009). We found no impact of WPRT on bPFS (HR = 0.79 [95% CI: 0.49 - 1.25], p = 0.31) or DFS (HR = 0.97 [95% CI: 0.63 - 1.49], p = 0.88). Only a positive surgical margin was an independent prognostic factor for better bPFS. Age≥63 years and WPRT (HR = 2.86 [95% CI: 1.20-6.80], p = 0.018) were independent prognostic factors for worse OS. Conclusions: After radical prostatectomy, we found no difference on bPFS or DFS but lower rates of OS with WPRT compared to PBRT. PBRT must remain the standard of care. The results of RTOG NRG Oncology 0534 should shed light on this unresolved issue.
Molecular Testing of Nodules with a Suspicious or Malignant Cytologic Diagnosis in the Setting of Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP)
Authors: Kyle C. Strickland, Markus Eszlinger, Ralf Paschke, Trevor E. Angell, Erik K. Alexander, Ellen Marqusee, Matthew A. Nehs, Vickie Y. Jo, Alarice Lowe, Marina Vivero, Monica Hollowell, Xiaohua Qian, Tad Wieczorek, Christopher A. French, Lisa A. Teot, Edmund S. Cibas, Neal I. Lindeman, Jeffrey F. Krane, Justine A. Barletta
Journal: Endocrine Pathology (2018)
Regulation of age-associated B cells by IRF5 in systemic autoimmunity
Authors: Michela Manni, Sanjay Gupta, Edd Ricker, Yurii Chinenov, Sung Ho Park, Man Shi, Tania Pannellini, Rolf Jessberger, Lionel B. Ivashkiv, Alessandra B. Pernis
Journal: Nature Immunology (2018)
I would like to work in intensive care medicine in Australia, especially cities such as Sydney, Melbourne, and Perth. How do I apply and what are the requirements?
Authors: Peter Shirley
Journal: BMJ (2004)

<i>Got 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.</i>
Fecal transplant by oral capsule was noninferior to delivery by colonoscopy for <i>C difficile</i> recurrence
Authors: Giannoula S. Tansarli, Eleftherios Mylonakis
Journal: Annals of Internal Medicine (2018)

Source Citation Kao D, Roach B, Silva M, et al. Effect of oral capsule- vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection: a randomized clinical trial. JAMA. 2017;318:1985-93. 29183074
Abstract 15746: Cardiac PI3K{gamma} Regulates GSK-3 Independent Of Akt By Scaffolding PP2A
Authors: Maradumane L Mohan, Neelakantan T Vasudevan, Manveen K Gupta, Elizabeth E Martelli, Sathyamangla V Naga Prasad
Journal: Circulation (2011)

G-protein coupled receptor activation of phosphoinositide 3-kinase γ (PI3Kγ) regulates glycogen synthase kinase-3 (GSK-3) via protein kinase B (Akt) mediating cardiac hypertrophy. We show here that...
Guidance needed for consultants working for private providers, says BMA
Authors: Abi Rimmer
Journal: BMJ (2016)

Doctors have called on the BMA to create guidance for consultants who work for private companies but treat NHS patients.

Delegates at the BMA Annual Representatives’ Meeting in Belfast on Tuesday 21 June passed a motion which called for guidance for consultants “who treat NHS patients but are no longer employed by NHS trusts.”

Gordon Mathews, ‎a consultant orthopaedic surgeon, said that a “significant volume” of NHS elective surgery was now done in private hospitals. “You may not like …
Professor Dame Carol Black, chairman of the Academy of Medical Royal Colleges and immediate past president of the Royal College of Physicians
Authors: Hannah Peters
Journal: BMJ (2007)

“When I started medical school I had already completed a history degree. At the time it felt like I had wasted time and was behind everyone else. I was seven years older than most medical students starting at 18. There was no fast track graduate entry programme in those days. My course was six years long. In hindsight, however, the sacrifices I had to make as a graduate were a great motivating force. Having no financial support, making a firm career choice early on, and pursuing that choice were crucial.

“When I qualified the knowledge I needed to be a good doctor did not emerge overnight. I was fortunate, however, that I was well looked after by my extremely supportive registrar. I continued to learn after graduating, under this good support. …
RECURRENCE OF STROKE IN CLOSURE OF PATENT FORAMEN OVALE VERSUS MEDICAL THERAPY IN PATIENTS WITH CRYPTOGENIC STROKE: SYSTEMIC REVIEW AND META-ANALYSIS
Authors: Usama Nasir, Waqas Qureshi, Abhishek Dutta, Hanumantha Jogu, Fahd Farooq, Mouaz Al-Mallah
Journal: Journal of the American College of Cardiology (2018)
CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss
Authors: Tal Teitz, Jie Fang, Asli N. Goktug, Justine D. Bonga, Shiyong Diao, Robert A. Hazlitt, Luigi Iconaru, Marie Morfouace, Duane Currier, Yinmei Zhou, Robyn A. Umans, Michael R. Taylor, Cheng Cheng, Jaeki Min, Burgess Freeman, Junmin Peng, Martine F. Roussel, Richard Kriwacki, R. Kiplin Guy, Taosheng Chen, Jian Zuo
Journal: The Journal of Experimental Medicine (2018)

Hearing loss caused by aging, noise, cisplatin toxicity, or other insults affects 360 million people worldwide, but there are no Food and Drug Administration-approved drugs to prevent or treat it. We screened 4,385 small molecules in a cochlear cell line and identified 10 compounds that protected against cisplatin toxicity in mouse cochlear explants. Among them, kenpaullone, an inhibitor of multiple kinases, including cyclin-dependent kinase 2 (CDK2), protected zebrafish lateral-line neuromasts from cisplatin toxicity and, when delivered locally, protected adult mice and rats against cisplatin- and noise-induced hearing loss. CDK2-deficient mice displayed enhanced resistance to cisplatin toxicity in cochlear explants and to cisplatin- and noise-induced hearing loss in vivo. Mechanistically, we showed that kenpaullone directly inhibits CDK2 kinase activity and reduces cisplatin-induced mitochondrial production of reactive oxygen species, thereby enhancing cell survival. Our experiments have revealed the proapoptotic function of CDK2 in postmitotic cochlear cells and have identified promising therapeutics for preventing hearing loss.
Reirradiation for recurrent glioma
Authors: Aoife Williamson, Mairi Mackinnon, Allan James, Anthony Chalmers, Stefan Nowicki
Journal: Neuro-Oncology (2018)

14 patients who received re-irradiation for recurrent glioma were identified. GTV was defined as the contrast-enhancing lesion on T1 MRI. No CTV was defined. Median GTV- PTV margin was 1.25cm. All patients received VMAT, 2 non co-planar arcs. The dose was 30Gy in 5 fractions. A cohort of 22 recurrent glioma patients was also identified. This group did not receive reirradiation. Reirrradiation cohort: Median age was 49. 5 patients had GBM, 2 had astrocytoma and 7 had oligodendroglioma. All LGG patients had radiological evidence of transformation to higher grade. At time of re-irradiation, patients had a mean KPS of 70% and had progressed through at least one line of chemo. 1 week post XRT median KPS was 70%. 1 month post XRT median KPS was 90%. Median dexamethasone dose was 2mg pre-XRT, 4mg 1 week post XRT and 4 mg 1 month post XRT. No severe acute or late complications were observed. PFS from irradiation was 4.2 months for GBM, 6.1 months for LGG. Median survival from reirradiation was 8 months for GBM and 11 months for LGG. Median OS from diagnosis for GBM was 34 months, and 126 months for LGG. A similar cohort of patients aged <65, KPS >70% who had progressed through at least one line of chemo after primary xrt were identified. 12 were GBM patients: median survival from 2nd line treatment was 11 months, median OS was 31 months. 10 LGG patients were identified with a median survival from 2nd line treatment of 12 months and median OS was 61.5 months. Conclusion Re-irradiation is a safe and feasible treatment. The majority of patients experienced an improvement in PS after treatment. However in this small, retrospective study there was no signal that reirradiation was associated with improved survival when compared with similar cohorts managed without reirradiation.