tbuckley/cabot-search huggingface dataset:
Retraining: scary but worth it
Authors: Christopher Bulstrode
Journal: BMJ (2004)

I have worked as an academic orthopaedic surgeon for more than 15 years. However, during one of my career reorganisations about five years ago I somehow lost my operating lists and outpatient clinics. Nobody seemed to mind much, and I felt I was probably doing everyone else a favour, particularly as there was such an unholy battle for operating lists in the hospital at the time. I continued to see patients in the emergency department when I was teaching students. I did medical reports and soldiered away writing textbooks. Then last year, at my appraisal, I decided that I should return to full orthopaedic surgical practice, both for my own professional satisfaction and so that I could explore the practicalities of retraining surgeons who had not been operating for whatever reason or who had been suspended by the General Medical Council (GMC).

It was clear to me that the quickest way to become competent in surgery again was to concentrate on retraining in a limited range of simple operations. I needed to find a busy unit which would accept me, but I also needed to be careful not …
Tumoroid à la carte: Path for personalization
Authors: Kyle Lewis, Takanori Takebe
Journal: Hepatology (2018)

1Division of Gastroenterology, Hepatology & Nutrition Developmental Biology Center for Stem Cell and Organoid MedicineCincinnati Children's Hospital Medical CenterCincinnatiOH 2Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiOH 3Advanced Medical Research CenterYokohama City UniversityYokohamaKanagawaJapan 4Institute of ResearchTokyo Medical and Dental UniversityTokyoJapan
Vascular smooth muscle contraction in hypertension
Authors: Rhian M Touyz, Rheure Alves-Lopes, Francisco J Rios, Livia L Camargo, Aikaterini Anagnostopoulou, Anders Arner, Augusto C Montezano
Journal: Cardiovascular Research (2018)

Hypertension is a major risk factor for many common chronic diseases, such as heart failure, myocardial infarction, stroke, vascular dementia, and chronic kidney disease. Pathophysiological mechanisms contributing to the development of hypertension include increased vascular resistance, determined in large part by reduced vascular diameter due to increased vascular contraction and arterial remodelling. These processes are regulated by complex-interacting systems such as the renin-angiotensin-aldosterone system, sympathetic nervous system, immune activation, and oxidative stress, which influence vascular smooth muscle function. Vascular smooth muscle cells are highly plastic and in pathological conditions undergo phenotypic changes from a contractile to a proliferative state. Vascular smooth muscle contraction is triggered by an increase in intracellular free calcium concentration ([Ca2+]i), promoting actin–myosin cross-bridge formation. Growing evidence indicates that contraction is also regulated by calcium-independent mechanisms involving RhoA-Rho kinase, protein Kinase C and mitogen-activated protein kinase signalling, reactive oxygen species, and reorganization of the actin cytoskeleton. Activation of immune/inflammatory pathways and non-coding RNAs are also emerging as important regulators of vascular function. Vascular smooth muscle cell [Ca2+]i not only determines the contractile state but also influences activity of many calcium-dependent transcription factors and proteins thereby impacting the cellular phenotype and function. Perturbations in vascular smooth muscle cell signalling and altered function influence vascular reactivity and tone, important determinants of vascular resistance and blood pressure. Here, we discuss mechanisms regulating vascular reactivity and contraction in physiological and pathophysiological conditions and highlight some new advances in the field, focusing specifically on hypertension.
The β2 Integrin Mac-1 Induces Protective LC3-Associated Phagocytosis of Listeria monocytogenes
Authors: Alexander Gluschko, Marc Herb, Katja Wiegmann, Oleg Krut, Wolfram F. Neiss, Olaf Utermöhlen, Martin Krönke, Michael Schramm
Journal: Cell Host & Microbe (2018)
Abstract 18049: Chromosome Content of Cardiac Progenitor Cells Influences Regenerative Potential of the Heart
Authors: Kathleen Broughton, Tiffany Khieu, Nicky Nguyen, Sadia Mohsin, Dieter Khubli, Pearl Quijada, Jessica Wang, Megan Monsanto, Natalie Gude, Mark Sussman
Journal: Circulation (2016)

Introduction: Discovery of endogenous stem cells in the heart, cardiac progenitor cells (CPC), has prompted intense basic discovery in multiple experimental animal models and clinical trials in hea...
GP recruitment rose in 2015, but more work is needed, says HEE
Authors: Abi Rimmer
Journal: BMJ (2015)

The number of trainees recruited into general practice increased in 2015, Health Education England (HEE) has announced. 

GP recruitment opened for a third round in July this year.1 Normally two rounds of GP recruitment take place, but in 2014 and 2015 HEE opened a third round to boost uptake.2

HEE said that 180 doctors had been accepted into GP training through the third round of recruitment in 2015, more than triple the 47 in 2014. Overall, annual GP fill rates had increased by two percentage points: from just over 87% in 2014 to nearly …
Professor Robert Lechler, vice principal, health, and dean, School of Medicine and Dental Institute at Guy’s, King’s, and St Thomas’ Hospitals, King’s College London
Authors: Hannah Peters
Journal: BMJ (2008)

When I left medical school I had to relearn much of what I had been taught. In those days, the medical curriculum at Manchester was highly compartmentalised. Biochemistry, anatomy, physiology, and so on were taught as distinct subjects. This made it quite hard, for example, to apply knowledge of pharmacology to therapeutics.

I was taught little or nothing about communication skills. Some people are naturally great communicators and others are less good, no matter how much teaching they receive. Role play and video recordings of yourself are undeniably useful tools that I had no access to as a medical student. Often you do not realise how you are perceived. If lessons in communication skills achieve nothing else, they should at least make students conscious of the importance of good communication. Similarly, the use …
Tunable and sustained-release characteristics of venlafaxine hydrochloride from chitosan–carbomer matrix tablets based on in situ formed polyelectrolyte complex film coating
Authors: Xiaofei Zhang, Xiangqin Gu, Xiaodan Wang, Huimin Wang, Shirui Mao
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good system robustness and simple preparation process. Taking venlafaxine hydrochloride (VH) as a drug model, the feasibility of using chitosan (CS), carbomer (CBM) combination system to achieve this goal was studied. Formulation and process variables influencing drug release from CS-CBM matrix tablets were investigated. It was found that CS-CBM combination system weakened the potential influence of CS, CBM material properties and gastric emptying time on drug release profile. Demonstrated by direct observation, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), in situ self-assembled polyelectrolyte complex (PEC) film was formed on the tablet surface during gastrointestinal tract transition, which contributed to the tunable and robust control of drug release. The sustained drug release behavior was further demonstrated in vivo in Beagle dogs, with level A in vitro and in vivo correlation (IVIVC) established successfully. In conclusion, CS-CBM matrix tablets are promising system to tune and control the release of highly water-soluble drugs with good system robustness.
IMPACT OF OBSTRUCTIVE SLEEP APNEA IN PATIENTS HOSPITALIZED FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION: A NATIONWIDE ANALYSIS
Authors: Bing Yue, Chayakrit Krittanawong, Xin Wei, Abel Casso Dominguez, Shuyang Fang, Mariam Khandaker, Mike Gorenchtein, Eyal Herzog
Journal: Journal of the American College of Cardiology (2018)
NHS England outlines review of funding allocation for CCGs
Authors: Helen Jaques
Journal: BMJ (2013)

NHS England is undertaking a “fundamental review” of how it allocates funding to clinical commissioning groups (CCGs), after concerns were expressed about the formula it had intended to use for 2013-14.

NHS England has published details of how CCGs across England would have fared if it had used the allocation formula proposed by the Advisory Committee on Resource Allocation to set funding for 2013-14. NHS England was concerned that the formula would move money …
Formulation and evaluation of gels containing coconut kernel extract for topical application
Authors: Wantanwa Krongrawa, Sontaya Limmatvapirat, Nushjira Pongnimitprasert, Paranee Meetam, Chutima Limmatvapirat
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The biological activity of coconut (Cocos nucifera L.) extracts from its kernels and various parts was reported by many previous studies, it is therefore believable that the extracts of its kernels might show some activities in topical formulations. Among several kernel extracts, the TC06 extract prepared by soaking the steamed coconut kernels in hot water showed the highest total phenolic content (6.98 ± 0.30 mg GAE/g extract) and the strongest antioxidant activity as determined using FRAP and DPPH methods with a reducing power value of 4.12 ± 0.16 mg AAE/g of extract and an SC50 value of 2.38 ± 0.14 mg/ml, respectively. In addition, this extract did not display any cytotoxic effects in the concentration range of 50-3200 µg/ml. Meanwhile, it revealed cytoprotective effects against t-BHP-induced cytotoxicity in HaCaT cells at concentrations higher than 400 µg/ml. The results of phytochemical investigations including a chemical color test, TLC, 1H NMR and FTIR suggested that the TC06 extract was mainly composed of flavonoids and terpenoids. Furthermore, the concentrations of heavy metals including As, Cd, Hg, and Pb in the TC06 extract were below permissible limits. According to the solubility, the TC06 extract was incorporated into gels using Carbopol Ultrez 21 as a gelling agent. The formulated gel containing 3% (w/w) TC06 extract was stable at 4 °C and 25 °C with 75% RH throughout the storage period. It was found that the Carbopol Ultrez 21-based hydroalcoholic gel containing an aqueous extract of coconut kernels exhibited antioxidant activities in the two assays and showed a sufficient consistency, a pleasing color, and a non-oily perception during the period of observation.
A Magnetic Resonance Imaging–Based Prediction Model for Prostate Biopsy Risk Stratification
Authors: Sherif Mehralivand, Joanna H. Shih, Soroush Rais-Bahrami, Aytekin Oto, Sandra Bednarova, Jeffrey W. Nix, John V. Thomas, Jennifer B. Gordetsky, Sonia Gaur, Stephanie A. Harmon, Mohummad Minhaj Siddiqui, Maria J. Merino, Howard L. Parnes, Bradford J. Wood, Peter A. Pinto, Peter L. Choyke, Baris Turkbey
Journal: JAMA Oncology (2018)

Multiparametric magnetic resonance imaging (MRI) in conjunction with MRI-transrectal ultrasound (TRUS) fusion-guided biopsies have improved the detection of prostate cancer. It is unclear whether MRI itself adds additional value to multivariable prediction models based on clinical parameters.To determine whether an MRI-based prediction model can reduce unnecessary biopsies in patients with suspected prostate cancer.Patients underwent MRI, MRI-TRUS fusion-guided biopsy, and 12-core systematic biopsy in 1 session. The development cohort used to derive the prediction model consisted of 400 patients from 1 institution enrolled between May 14, 2015, and August 31, 2016, and the validation cohort included 251 patients from 2 independent institutions who underwent biopsies between April 1, 2013, and June 30, 2016, at 1 institution and between July 1, 2015, and October 31, 2016, at the other institution. The MRI model included MRI-derived parameters in addition to clinical variables. Area under the curve of receiver operating characteristic curves and decision curve analysis were performed.Risk of clinically significant prostate cancer on biopsy, defined as a Gleason score of 3 + 4 or higher in at least 1 biopsy core.Overall, 193 (48.3%) of the 400 patients in the development cohort (mean [SD] age at biopsy, 64.3 [7.1] years) and 96 (38.2%) of the 251 patients in the validation cohort (mean [SD] age at biopsy, 64.9 [7.2] years) had clinically significant prostate cancer, defined as a Gleason score greater than or equal to 3 + 4. By applying the model to the external validation cohort, the area under the curve increased from 64% to 84% compared with the baseline model (P < .001). At a risk threshold of 20%, the MRI model had a lower false-positive rate than the baseline model (46% [95% CI, 32%-66%] vs 92% [95% CI, 70%-100%]), with only a small reduction in the true-positive rate (89% [95% CI, 85%-96%] vs 99% [95% CI, 89%-100%]). Eighteen of 100 fewer biopsies could have been performed, with no increase in the number of patients with missed clinically significant prostate cancers.The inclusion of MRI-derived parameters in a risk model could reduce the number of unnecessary biopsies while maintaining a high rate of diagnosis of clinically significant prostate cancers.
GP who altered notes of patient who died after DVT was missed is suspended
Authors: Clare Dyer
Journal: BMJ (2018)

A GP has been suspended from the UK medical register for 12 months after he missed deep vein thrombosis in a patient’s leg and altered her notes after her death four days later.

Fardeen Haque was investigated by police for gross negligence manslaughter and attempting to pervert the course of justice. He was tried at a crown court for attempting to pervert the course of justice but was acquitted.

Haque saw Patient A at Flagg Court Health Centre in South Shields on 1 March 2013 and provisionally diagnosed a Baker’s cyst, a swelling at the back of the knee. He also asked her to arrange an appointment to investigate osteoarthritis.

On 5 March the patient collapsed and was taken to hospital but died on the way. A postmortem examination on 16 March found massive bilateral coiled thromboemboli of …
CLINICAL AND ELECTROCARDIOGRAPHIC CHARACTERISTICS IN PATIENTS WITH FULMINANT MYOCARDITIS
Authors: Tomonori Itoh, Jun Anzai, Yuya Oshikiri, Takamasa Kobayashi, Yumeka Arakawa, Mamoru Satoh, Motoyuki Nakamura, Yoshihiro Morino
Journal: Journal of the American College of Cardiology (2018)
Domestically Produced Radioisotope
Authors: Rebecca Voelker
Journal: JAMA (2018)

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Discordance rate of PD-L1 expression between primary and metastatic lesions in urothelial carcinoma (UC).
Authors: Earle Frederick Burgess, Caroline Naso, Shannon Doherty, Renato Guerrieri, Chad Livasy, Aaron Hartman, Myra M. Robinson, James Thomas Symanowski, Claud Grigg, David L. Graham, Kwabena Osei-Boateng, Stephen Boyd Riggs, Peter Clark, Derek Raghavan
Journal: Journal of Clinical Oncology (2018)

493 Background: Immune checkpoint inhibitors (ICI) targeting PD-1 or PD-L1 are effective in select patients with advanced UC. High PD-L1 expression enriches for response to ICIs; however, the predictive value of PD-L1 expression is limited, which may be due in part to dynamic expression of PD-L1 in the tumor environment. We sought to characterize PD-L1 expression in primary UC and paired metastatic lesions to gain insight into the potential temporal discordance of tumor PD-L1 expression during the metastatic process. Methods: Immunohistochemical (IHC) staining for PD-L1 using the SP-142 antibody was performed on primary tumors and matched metastatic specimens in 83 patients with advanced UC. IHC staining was scored for the percentage of cells positive ( &lt; 5%, ≥5%) in tumor cell (TC) and immune cell (IC) compartments. Correlation of PD-L1 expression in TCs and ICs was estimated using Spearman’s correlation coefficients (ρ). Cohen’s kappa statistics (κ) were utilized to assess the agreement in PD-L1 expression between groups. Results: High (≥5%) PD-L1 expression in primary and metastatic biopsies, respectively, was observed in 6.1% and 14.6% of TCs and in 7.8% and 11.7% of ICs. High co-expression of PD-L1 in both TC and IC compartments was infrequent in primary and metastatic lesions (3.6% and 2.6%, respectively). PD-L1 expression in TCs was positively correlated with PD-L1 expression in ICs in primary tumors (ρ = 0.47) and in metastatic lesions (ρ = 0.27). TC PD-L1 expression in primary tumors was correlated with TC PD-L1 expression in paired metastatic lesions (ρ = 0.44) but there was minimal agreement in high expression rates between primary and metastatic lesions in the TC compartment (κ = 0.147). IC PD-L1 expression in primary tumors was not correlated with IC PD-L1 expression in paired metastatic lesions (ρ = 0.05) and there was poor agreement in high expression rates between primary and metastatic lesions in the IC compartment (κ = 0.086). Conclusions: High PD-L1 IC expression is temporally discordant between primary and metastatic UC lesions. Future studies of PD-1/PD-L1 targeted therapies in patients with metastatic UC should utilize recent biopsies of metastatic lesions to define PD-L1 expression when feasible.
A consultant ophthalmologist
Authors: Antonella Berry-Brincat
Journal: BMJ (2006)

Raymond Brown gives up his own time and expertise to improve eye care in Paraguay. Mr Brown has set up an international link between University Hospital of North Staffordshire and Asuncion, Paraguay. He trains local surgeons, has started screening programmes for retinopathy of prematurity, and introduced the concept of orthoptic care to reduce the burden of childhood visual disability.
Impact of number of cycles of platinum-based first-line chemotherapy for advanced urothelial carcinoma.
Authors: Andrea Necchi, Luigi Mariani, Salvatore Lo Vullo, Daniele Raggi, Patrizia Giannatempo, Aristotelis Bamias, Simon J. Crabb, Joaquim Bellmunt, Evan Y. Yu, Guenter Niegisch, Ulka N. Vaishampayan, Christine Theodore, Dominik R. Berthold, Sandy Srinivas, Srikala S. Sridhar, Elizabeth R. Plimack, Jonathan E. Rosenberg, Thomas Powles, Matthew Galsky, Guru Sonpavde
Journal: Journal of Clinical Oncology (2018)

426 Background: 6 cycles of platinum-based chemotherapy (CT) are conventionally targeted to treat locally advanced unresectable or metastatic urothelial carcinoma (UC). However, cisplatin is associated with significant cumulative toxicities, which render it challenging to deliver 6 cycles. Since this issue has not been investigated prospectively, we conducted a retrospective analysis. Methods: The Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC) database was used to conduct a retrospective analysis. The association of the number of cycles of platinum-based first-line CT with overall survival (OS) was investigated by a Cox regression utilizing multivariate analysis after controlling for previously recognized prognostic factors used in a nomogram ( Eur Urol, 2017). The primary analysis was a comparison of &lt; 6 cycles vs. ≥6 cycles. Six-month landmark analysis was applied throughout, accounting for OS events. Additionally, we excluded patients (pts) receiving &lt; 3 or &gt; 9 cycles to reduce confounding due to early removal for toxicities, progression and patient decision and increased number of cycles due to response and pt-related factors. Results: Of 1020 pts available from RISC, 472 (cisplatin = 338, carboplatin = 134) were evaluable for the landmark analysis with 281 events. A total of 157 pts received 3-5 cycles (median 4) and 315 received 6-9 cycles (median 6). There was no significant difference between 3-5 vs. 6-9 cycles of platinum-based chemotherapy (HR 1.02, 95%CI: 0.77-1.33, p = 0.91). No significant interactions were observed with type of platinum (p = 0.09) and “completed planned CT” (p = 0.56). Comparison of 4 vs. 6 cycles (p = 0.57) and &lt; 6 vs 6 vs 7-9 (p = 0.9) also yielded no significant differences for association with OS. No differential association was observed with survival for 3-5 vs. 6-9 cycles when examining by nomogram-defined risk group tertiles. Limitations of a hypothesis-generating retrospective analysis apply. Conclusions: 4 cycles of platinum based first-line CT appear adequate to treat advanced UC. The omission of excessive cycles will avoid unnecessary toxicities and facilitate better transition to second-line and switch maintenance therapy.
Drawing for surgeons
Authors: Susie Yao
Journal: BMJ (2010)

The course is suitable for any medical professional with an interest in developing their artistic talents. Although the title of the course is “Drawing for surgeons,” physicians are also welcome. Medical “artists” at all levels of ability are invited to gain skills that will promote better communication with patients and colleagues alike, such as through anatomical diagrams and operation notes. 

This year an international mix of candidates attended the course, with people coming from Ireland, Italy, and Austria. Although only surgeons attended this time, a variety of specialties and grades of doctors were represented, including urology, orthopaedic, and maxillofacial consultants; paediatric surgical registrars; and ear, nose, and throat and plastic surgery senior house officers.

I have always enjoyed art from my school years through to university, and at work I have tried to use my abilities to produce …