tbuckley/cabot-search huggingface dataset:
Direct‐acting antivirals do not increase the risk of hepatocellular carcinoma recurrence after local‐regional therapy or liver transplant waitlist dropout
Authors: Annsa C. Huang, Neil Mehta, Jennifer L. Dodge, Francis Y. Yao, Norah A. Terrault
Journal: Hepatology (2018)

Whether direct‐acting antivirals (DAAs) increase the risk of hepatocellular carcinoma (HCC) recurrence after tumor‐directed therapy is controversial. We sought to determine the impact of DAA therapy on HCC recurrence after local‐regional therapy (LRT) and waitlist dropout among liver transplant (LT) candidates with HCC. We performed a retrospective cohort study of 149 LT candidates with hepatitis C virus (HCV) and HCC at a single center from 2014 through 2016. Cumulative incidence of HCC recurrence post‐LRT and waitlist dropout was estimated by the DAA group. Factors associated with each outcome were evaluated using competing risks regression. A propensity score stabilized inverse probability weighting approach was used to account for differences in baseline characteristics between groups. The no DAA group (n = 87) had more severe cirrhosis and lower rates of complete radiologic tumor response after LRT than those treated with DAA (n = 62) but had similar alpha‐fetoprotein and tumor burden at listing. Cumulative incidence of HCC recurrence within 1 year of complete response after LRT was 47.0% in the DAA group and 49.8% in the no DAA group ( P = 0.93). In adjusted competing risk analysis using weighted propensity score modeling, risk of HCC recurrence was similar in the DAA group compared to those without DAA (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.58‐1.42; P = 0.67). Patients treated with DAAs had lower risk of waitlist dropout due to tumor progression or death compared to the no DAA group in adjusted weighted analysis (HR, 0.30; 95% CI 0.13‐0.69; P = 0.005). Conclusion : In LT candidates with HCV and HCC with initial complete response to LRT, DAA use is not associated with increased risk of HCC recurrence but rather is associated with reduced risk of waitlist dropout due to tumor progression or death. (H epatology 2018).
The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China—recommendations from the Chinese Society of Hematology
Authors: Lanping Xu, Hu Chen, Jing Chen, Mingzhe Han, He Huang, Yongrong Lai, Daihong Liu, Qifa Liu, Ting Liu, Ming Jiang, Hanyun Ren, Yongping Song, Zimin Sun, Jianmin Wang, Depei Wu, Daobin Zhou, Ping Zou, Kaiyan Liu, Xiaojun Huang
Journal: Journal of Hematology & Oncology (2018)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used to treat malignant hematological neoplasms and non-malignant hematological disorders. Approximately, 5000 allo-HSCT procedures are performed in China annually. Substantial progress has been made in haploidentical HSCT (HID-HSCT), pre-transplantation risk stratification, and donor selection in allo-HSCT, especially after the establishment of the "Beijing Protocol" HID-HSCT system. Transplant indications for selected subgroups in low-risk leukemia or severe aplastic anemia (SAA) differ from those in the Western world. These unique systems developed by Chinese doctors may inspire the refining of global clinical practice. We reviewed the efficacy of allo-HSCT practice from available Chinese studies on behalf of the HSCT workgroup of the Chinese Society of Hematology, Chinese Medical Association and compared these studies to the consensus or guideline outside China. We summarized the consensus on routine practices of all-HSCT in China and focused on the recommendations of indications, conditioning regimen, and donor selection.
I am a first year resident in radiology at the Moscow medical academy in Sechenov, currently posted at the Russian cardiac research centre. I want to work as a radiologist in the United Kingdom. What are the requirements to gain training there?
Authors: Alan Denison
Journal: BMJ (2006)

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. <b>www.bmjcareers.com/advicezone</b>
AUTOMATED IDENTIFICATION OF SUDDEN DEATH RISK PHENOTYPES FROM ELECTRONIC HEALTH RECORDS OF PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY
Authors: Sungrim Moon, Sujith Samudrala, Sijia Liu, Jane L. Shellum, Steve Ommen, Rick A. Nishimura, Hongfang Liu, Adelaide Arruda-Olson
Journal: Journal of the American College of Cardiology (2018)
UK guidelines on oesophageal dilatation in clinical practice
Authors: Sarmed S Sami, Hasan N Haboubi, Yeng Ang, Philip Boger, Pradeep Bhandari, John de Caestecker, Helen Griffiths, Rehan Haidry, Hans-Ulrich Laasch, Praful Patel, Stuart Paterson, Krish Ragunath, Peter Watson, Peter D Siersema, Stephen E Attwood
Journal: Gut (2018)

These are updated guidelines which supersede the original version published in 2004. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG. The original guidelines have undergone extensive revision by the 16 members of the Guideline Development Group with representation from individuals across all relevant disciplines, including the Heartburn Cancer UK charity, a nursing representative and a patient representative. The methodological rigour and transparency of the guideline development processes were appraised using the revised Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.Dilatation of the oesophagus is a relatively high-risk intervention, and is required by an increasing range of disease states. Moreover, there is scarcity of evidence in the literature to guide clinicians on how to safely perform this procedure. These guidelines deal specifically with the dilatation procedure using balloon or bougie devices as a primary treatment strategy for non-malignant narrowing of the oesophagus. The use of stents is outside the remit of this paper; however, for cases of dilatation failure, alternative techniques-including stents-will be listed. The guideline is divided into the following subheadings: (1) patient preparation; (2) the dilatation procedure; (3) aftercare and (4) disease-specific considerations. A systematic literature search was performed. The Grading of Recommendations Assessment, Develop-ment and Evaluation (GRADE) tool was used to evaluate the quality of evidence and decide on the strength of recommendations made.
Novel therapeutic strategy to inhibit growth of pancreatic cancer organoids using a rational combination of drugs to induce mitotic arrest and apoptosis.
Authors: Zhijian Duan, Mei-Juan Tu, Qianyu Zhang, May Thet Cho, Jasmine Huynh, Aiming Yu, Edward Jae-hoon Kim
Journal: Journal of Clinical Oncology (2018)

322 Background: The ability of cancer cells to suppress apoptosis is critical for carcinogenesis. The Bcl-2-family of regulator proteins, including the anti-apoptotic members Bcl-2, Bcl-xL and Mcl-1, contributes to a complex network in control of apoptosis. BH3-mimetics (e.g. ABT-263) can inhibit anti-apoptotic Bcl-2 proteins and therefore have been developed as potential cancer therapeutics. Aurora Kinase A (AKA) is over-expressed in pancreatic cancer (PC) and is expressed to regulate G2-M transition during mitosis, making it an attractive target for PC. In this study we hypothesized that a combination of mitotic arrest using an AKA inhibitor (e.g. MLN8237) would sensitize PC to induction of apoptosis by a BH3-mimetic. Methods: Pancreatic cell lines (AsPC-1, PANC-1, MIA PaCa-2, HPAF-II) and patient-derived pancreatic cancer organoids (PDO) were treated with a BH3-mimetic (ABT-263) alone, an AKA inhibitor (MLN8237) alone, or the combination in comparison to untreated controls. Cell viability was measured using the CellTiter-Fluor (Promega) assay. Apoptosis was evaluated by Western blot (WB) for cleaved PARP, caspase 3 or caspase 7, and flow cytometry. Nude mice were implanted with pancreatic cancer cells to generate PC xenografts which were then treated with the same 4 treatment groups as in the in vitro studies. Results: ABT-263 combined with MLN8237 showed greater potency than either single drug alone, demonstrating synergy in inhibiting the growth of PC cells and PDOs. Combined treatment with MLN8237 and ABT-263 in PDOs suppressed organoid formation and proliferation by inducing apoptosis. Mechanistically, MLN8237 enhanced the activity of ABT-263 through reduction of Bcl-xL and Mcl-1 in pancreatic cancer cell lines and PDOs. The combination therapy also showed greater suppression of the growth of xenograft tumors, as compared with control treatments with single drug alone or vehicle. Conclusions: The combination of ABT-263 and MLN8237 appears to synergistically induce apoptosis via reduction of Bcl-2 family proteins in PC and should be further explored.
Experience of a Brazilian oncological center using abiraterone acetate in metastatic castration-resistant prostate cancer patients.
Authors: Daniel D`Almeida Preto, Luis Eduardo Zucca, Flavio Mavignier Carcano, Ricardo Zylberberg, Joao Antonio Junior Neif, Carlos Alberto Fruet Filho
Journal: Journal of Clinical Oncology (2018)

364 Background: Abiraterone acetate (AA), a selective inhibitor of androgen biosynthesis, improves overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients. In Brazil, despite this medication has been approved by health regulatory agency since 2013, due to the high cost, few public services release to their patients. It's interesting to note that this drug configures the eighth most judicial request medication in the country, as the way brazilian constitution ensures equal treatment for all patients. Methods: We performed a unicenter retrospective cohort study of 45 patients with mCRPC, receiving AA after chemotherapy with docetaxel, in the period from 2014 to 2016. The primary end point was OS. The secondary end points included the epidemiological profile, assessing the type of access to medication (judicial request, health insurance and patient's resource) and PSA response rate. Results: The median OS was 15 months. The mean duration use of AA was 10.87 months (± 6.8). Most patients (75.6%) have filed a lawsuit to get the medication and the average time between the request and the application of AA was bigger in this judicial request group (2.7 vs 1.4 months). Biochemical response was evidenced in 39% of patients. Conclusions: Our unicenter data on post-Docetaxel use of AA improved overall survival in a select group of mCRPC patients, and it is in line with the COU-AA-301 trial. Cost effectiveness evaluations combining with a patient`s protocol should be performed in order to incorporate this medication into the brazilian public health system. Characteristics of the patients. [Table: see text]
Chronic Active Arthritis Driven by Macrophages Without Involvement of T Cells
Authors: Cecilia Hagert, Outi Sareila, Tiina Kelkka, Kutty Selva Nandakumar, Mattias Collin, Bingze Xu, Simon Guérard, Johan Bäcklund, Sirpa Jalkanen, Rikard Holmdahl
Journal: Arthritis & Rheumatology (2018)

Objective To develop a new chronic rheumatoid arthritis model that is driven by the innate immune system. Methods Injection of a cocktail of 4 monoclonal antibodies against type II collagen, followed on days 5 and 60 by intraperitoneal injections of mannan (from Saccharomyces cerevisiae ), was used to induce development of chronic arthritis in B10.Q mice. The role of the innate immune system as compared to the adaptive immune system in this arthritis model was investigated using genetically modified mouse strains. Results A new model of chronic relapsing arthritis was characterized in B10.Q mice, in which a persistently active, chronic disease was found. This relapsing disease was driven by macrophages lacking the ability to mount a reactive oxygen species response against pathogens, and was associated with the classical/alternative pathway, but not the lectin pathway, of complement activation. The disease was independent of Fcγ receptor type III , and also independent of the activity of adaptive immune cells (B and T cells), indicating that the innate immune system, involving complement activation, could be the sole driver of chronicity. Conclusion Chronic active arthritis can be driven innately by macrophages without the involvement of T and B cells in the adaptive immune system.
6-MONTH ECHOCARDIOGRAPHIC OUTCOME AFTER TRANSCATHETER TRICUSPID VALVE REPAIR IN 25 PATIENTS WITH SEVERE TRICUSPID REGURGITATION
Authors: Mathias Orban, Daniel Braun, Thomas Stocker, Diana Rösler, Andrea Englmaier, Steffen Massberg, Michael Nabauer
Journal: Journal of the American College of Cardiology (2018)
DNA Nanostructure‐Based Systems for Intelligent Delivery of Therapeutic Oligonucleotides
Authors: Qinqin Hu, Sheng Wang, Lihua Wang, Hongzhou Gu, Chunhai Fan
Journal: Advanced Healthcare Materials (2018)

In the beginning of the 21st century, therapeutic oligonucleotides have shown great potential for the treatment of many life‐threatening diseases. However, effective delivery of therapeutic oligonucleotides to the targeted location in vivo remains a major issue. As an emerging field, DNA nanotechnology is applied in many aspects including bioimaging, biosensing, and drug delivery. With sequence programming and optimization, a series of DNA nanostructures can be precisely engineered with defined size, shape, surface chemistry, and function. Simply with hybridization, therapeutic oligonucleotides including unmethylated cytosine–phosphate–guanine dinucleotide oligos, small interfering RNA (siRNA) or antisense RNA, single guide RNA of the regularly interspaced short palindromic repeat–Cas9 system, and aptamers, are successfully loaded on DNA nanostructures for delivery. In this progress report, the development history of DNA nanotechnology is first introduced, and then the mechanisms and means for cellular uptake of DNA nanostructures are discussed. Next, current approaches to deliver therapeutic oligonucleotides with DNA nanovehicles are summarized. In the end, the challenges and opportunities for DNA nanostructure‐based systems for the delivery of therapeutic oligonucleotides are discussed.
Letter by Jin-shan and Xue-bin Regarding Article, “Physiology of Angina and Its Alleviation With Nitroglycerin: Insights From Invasive Catheter Laboratory Measurements During Exercise”
Authors: He Jin-shan, Li Xue-bin
Journal: Circulation (2018)

We read with great interest the article presented by Asrress and colleagues 1 about the physiology of angina and its alleviation with nitroglycerin (NTG), which characterizes intracoronary physiological behavior of coronary stenosis during exercise before and after NTG and explains the physiological consequences directly related to angina relief (reducing myocardial oxygen demand and increasing supply).We have 2 questions about this article.First, β-blocker, calcium channel antagonist, and NTG are common drugs used to alleviate angina.Now that we have a clear understanding of NTG's effect on angina, can we study the physiological influence of the other 2 kinds of drugs in the same way?If so, we would have a better understanding of their difference in angina relief and could prescribe them appropriately for different patients.Second, all the patients' angina in the study group is alleviated by NTG, which is different from outcomes in real clinical practice.Patients with unstable symptoms, previous myocardial infarction, ejection fraction <50%, known left main stem disease, and severe multivessel coronary artery disease are all excluded.In the future, can we include these patients in the study?Cases with angina that cannot be relieved by NTG will show up and help us understand the physiological mechanism of NTG-resistant angina.Is it because of failure in reducing myocardial oxygen demand?Or increasing supply?We will manage patients with angina better with this information, especially those who are resistant to common therapy.
Childhood in Syria
Authors: Alison Shepherd
Journal: BMJ (2018)

Bassam Khabieh/Reuters

Wounded children, who are among the 12 000 civilian casualties of the Syrian regime’s month long siege, are treated in a dilapidated hospital in Douma, Eastern Ghouta.

International aid agencies have been urging the government to allow doctors and medical equipment into the besieged suburb of the capital, Damascus. Many health facilities …
Safety and efficacy of exposure to bedaquiline−delamanid in multidrug-resistant tuberculosis: a case series from France and Latvia
Authors: Lorenzo Guglielmetti, Linda Barkane, Damien Le Dû, Dhiba Marigot-Outtandy, Jérôme Robert, Nicolas Veziris, Yazdan Yazdanpanah, Liga Kuksa, Eric Caumes, Mathilde Fréchet-Jachym
Journal: European Respiratory Journal (2018)

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) represent a therapeutic challenge [1]. Two anti-TB agents, bedaquiline and delamanid, have been recently approved for the treatment of MDR/XDR-TB. Bedaquiline has a terminal half-life of 5.5 months, in contrast with the short half-life of delamanid (38 h). Both drugs increase the QTcF (Fridericia-corrected QT) interval, although no clinically significant cardiac events have been reported in patients treated with one of these drugs [2, 3]. The clinical trials that led to approval of bedaquiline and delamanid tested these drugs by adding one of them, for a duration of 24 weeks and 6–8 months, respectively, to optimised background [2, 3]. To date, only six cases treated with the bedaquiline−delamanid combination have been reported, mostly presenting interim results [4–6]. The World Health Organization (WHO) recommends to use these drugs for a standardised duration of 24 weeks, the concomitant use of bedaquiline and delamanid being restricted to patients with "no other therapeutic options". Otherwise, it is recommended to start the two drugs sequentially after a washout period of 6 months, when switching from bedaquiline to delamanid, and 5 days, when switching from delamanid to bedaquiline [7]. We report the results of exposure to concomitant and sequential treatment with bedaquiline and delamanid, including treatment courses beyond 24 weeks, as part of multidrug MDR/XDR-TB regimens. Good tolerability of exposure to bedaquiline−delamanid association in MDR/XDR-TB patients <http://ow.ly/4uvr30i7az4> The authors acknowledge Camille Diallo, Bénédicte Lemaire and Dominique Szmigiel-Perret for their help in conducting the study.
NICE recommends dropping all QOF indicators on depression
Authors: Helen Jaques
Journal: BMJ (2011)

The National Institute for Health and Clinical Excellence (NICE) has suggested retiring all indicators relating to depression from the Quality and Outcomes Framework (QOF), in its recommendations for QOF for 2012-13.

The institute’s QOF advisory committee believes that the supporting evidence for the depression indicators DEP01, DEP04, and DEP05 “gave rise to significant concerns” and that the indicators were not shown to be effective in improving care or health outcomes for people with depression. 

The committee also reported concerns from GPs that the indicators encourage a bureaucratic approach to identifying …
First trimester fetal size and prescribed asthma medication at 15 years of age
Authors: Steve Turner, Shona Fielding, Graham Devereux
Journal: European Respiratory Journal (2018)

There is increasing evidence that antenatal factors predispose to childhood asthma. We tested the hypothesis that reduced first trimester fetal size is associated with increased risk for asthma at 15 years of age.Fetal size in the first and second trimester was ascertained by ultrasound scan. The primary outcome of being dispensed one or more asthma medications by the family doctor in the year before the 15th birthday was determined from routinely acquired dispensing data.Dispensing data were available for 1699 (88% of the original cohort) participants at 15 years of age and questionnaire data for 750 (39%). Each reduction in z-score for first trimester size was associated with increased odds for dispensed asthma medication at 15 years of age (OR 1.26, 95% CI 1.03-1.54) and self-reported use of asthma medications (OR 1.55, 95% CI 1.16-2.08). Overall, first and second trimester size and forced expiratory volume in 1 s at ages 5, 10 and 15 years were reduced for those dispensed asthma medications compared with those not dispensed asthma medications (p=0.003).Antenatal factors that are active by the first trimester may contribute to respiratory well-being throughout childhood. Dropout from a birth cohort study can overestimate of the magnitude of any true association.
The essence of Ellis
Authors: Ray Parsons
Journal: BMJ (2007)

Your article about Professor Harold Ellis1 brought back many memories of my time as a medical student at Westminster Medical School in the early 1960s.

I consider I was extremely fortunate to have been taught by Professor Ellis. He had just been appointed to Westminster as the first professor of surgery there, together with Malcolm Milne. I was also fortunate to be taught and to work with …