tbuckley/cabot-search huggingface dataset:
Idelalisib and Rituximab in 17p Deletion–Positive Splenic Marginal Zone Lymphoma
Authors: Aby Z. Philip
Journal: Journal of the National Comprehensive Cancer Network (2018)

Splenic marginal zone lymphoma (SMZL) is a rare indolent B-cell malignancy involving the spleen and bone marrow. Various cytogenetic abnormalities with prognostic value have been identified in SMZL. Complexity of karyotype, 14q aberrations, and TP53 deletions have been found to be poor prognostic indicators. We report an unusual case of SMZL with a complex karyotype including 17p deletion, primarily refractory to 2 chemoimmunotherapy regimens, that responded well to treatment with phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitors idelalisib and rituximab.
通过电子皮镜观察到在后天性痣亚型中常见 BRAF 和 NRAS 突变,表现出组成型 MAPK 通路活化
Authors: J.M. Tan, L.N. Tom, K. Jagirdar, D. Lambie, H. Schaider, R.A. Sturm, H.P. Soyer, M.S. Stark
Journal: British Journal of Dermatology (2018)

大多数人的皮肤上都有几个褐斑,我们称之为黑素细胞痣或痣。痣对人体无害,但偶尔可能转化为潜在致死性肿瘤,也就是恶性黑色素瘤。在放大镜(电子皮镜)下,皮肤科专家通过外观确定了不同类型的痣。广义上:“球状”痣在早年出现,并且可能转化为黑色素瘤;“网状”痣在成年期出现,并且可能与未长痣部位出现的黑色素瘤有关;带“外围球状体”(PG) 的网状痣会生长,但非恶性。良性痣及癌性痣(恶性黑色素瘤)中都可能出现 BRAF 和 NRAS 基因突变(变异)。这些基因是在肿瘤形成中起重要作用的 MAPK 通路的成分。为说明这些基因的作用,这些来自澳大利亚的研究人员探讨了电子皮镜下外观与良性痣中的 NRAS 和 BRAF 突变之间的关系。他们通过电子皮镜检查了 27 人的 40 个后天性(非先天性)痣,然后去痣以进行分析。在显微镜下,研究人员观察到大多数网状痣中的细胞结构无序,但这种情况在球状痣以及 PG 痣中很少见。研究人员使用了一种能够检测单细胞突变的新型高灵敏度方法(“微滴式数字 PCR”),他们发现大多数球状痣以及所有 PG 痣都出现 BRAF 突变,网状痣则出现 BRAF 或 NRAS 突变。研究人员得出结论,所有痣具有 MAPK 基因突变,证明 MAPK 通路在黑素细胞痣及黑色素瘤的形成中起基础性作用。
Is anaesthetics a stressful career?
Authors: Peter Maguire
Journal: BMJ (2004)

<i>Got a career or related 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>
Sixty seconds on . . . the Presidents Club
Authors: Anne Gulland
Journal: BMJ (2018)

It’s seedy, but has nothing to do with the president of the United States. It’s an annual men only fundraising dinner, attended by City grandees and captains of industry, where a bevy of attractive, scantily clad young hostesses are exposed to behaviour bordering on sexual assault, including groping and nudity. An undercover reporter from the Financial Times infiltrated …
SEX DIFFERENCES IN CARDIOVASCULAR DISEASE OUTCOMES IN RESPONSE TO FENOFIBRATE THERAPY IN TYPE 2 DIABETIC PATIENTS IN THE ACCORD LIPID STUDY
Authors: Avantika Banerjee, Tejas Patel, Gyorgy Csako, Andrew Dodge, Eileen Navarro, Colin O. Wu, Tesfaldet Bereket, Md Shamsuzzaman, Jerome Fleg, Charu Gandotra, George Sopko, Helena Sviglin, Gauri Dandi, Sean Coady, Nashwan Farooque, Lawton Cooper, Iffat Chowdhury, Ana Szarfman, Karim Calis, Keith Burkhart, Carlos Cure, Frank Pucino, Yves Rosenberg, Ahmed Hasan
Journal: Journal of the American College of Cardiology (2018)
I have a passion for HIV and infectious diseases and dream to be a specialist in this field. What pathways are there? I will be eligible for GMC registration soon
Authors: Ronald McCoy
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>
Trends in Hospital Admission for Diabetic Ketoacidosis in Adults With Type 1 and Type 2 Diabetes in England, 1998–2013: A Retrospective Cohort Study
Authors: Victor W. Zhong, Juhaeri Juhaeri, Elizabeth J. Mayer-Davis
Journal: Diabetes Care (2018)

This study determined trends in hospital admission for diabetic ketoacidosis (DKA) in adults with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) from 1998 to 2013 in England.The study population included 23,246 adults with T1DM and 241,441 adults with T2DM from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES). All hospital admissions for DKA as the primary diagnosis from 1998 to 2013 were identified. Trends in hospital admission for DKA in incidence, length of hospital stay, 30-day all-cause readmission rate, and 30-day and 1-year all-cause mortality rates were determined using joinpoint regression, negative binomial regression, and logistic regression models.For T1DM, the incidence of hospital admission for DKA increased between 1998 and 2007 and remained static until 2013. The incidence in 2013 was higher than that in 1998 (incidence rate ratio 1.53 [95% CI 1.09-2.16]). For T2DM, the incidence increased 4.24% (2.82-5.69) annually between 1998 and 2013. The length of hospital stay decreased over time for both diabetes types (P ≤ 0.0004). Adults with T1DM were more likely to be discharged within 2 days compared with adults with T2DM (odds ratio [OR] 1.28 [1.07-1.53]). The 30-day readmission rate was higher in T1DM than in T2DM (OR 1.61 [1.04-2.50]) but remained unchanged for both diabetes types over time. Trends in 30-day and 1-year all-cause mortality rates were also stable, with no difference by diabetes type.In the previous two decades in England, hospitalization for DKA increased in adults with T1DM and in those with T2DM, and associated health care performance did not improve except decreased length of hospital stay.
Abstract P1-01-18: Disrupting interactions between human breast cancer cells, adipocytes, and macrophages
Authors: KA Vallega, Q-XA Sang
Journal: Cancer Research (2018)

Abstract An increasing number of studies have found that other cells in the tumor microenvironment can influence tumor cells. Adipocytes, which were once thought to function only in energy storage, are now considered an active endocrine organ that secretes pro-inflammatory cytokines and proteases. In human breast cancer patients, invading tumor cells are surrounded by mature adipocytes. The breast cancer cells cause the adipocytes to undergo phenotypic changes and overexpress pro-inflammatory cytokines and matrix metalloproteinases (MMPs), such as MMP-3 and MMP-11. The presence of the changed adipocytes then increases the invasion capacity of breast cancer cells. Obesity is an important breast cancer risk factor. It causes changes to adipocytes and the surrounding microenvironment by invasion of macrophage cells. The effects of obesity-induced macrophage invasion have not been well characterized in the sector of breast cancer-adipocyte crosstalk. A novel 3D co-culture system was used to investigate how macrophage-induced inflammation can worsen this crosstalk, and what changes are involved in cytokine expression, adipocyte de-differentiation, breast cancer aggressiveness, and extracellular matrix (ECM) composition. When macrophage conditioned media was added to adipocytes and breast cancer cells in co-culture, the breast cancer cells showed increased cell proliferation and migration abilities. Experimental co-culture (adipocytes, breast cancer cells, macrophage conditioned media) showed almost twice the number of cells than the control co-culture (adipocytes, breast cancer cells, non-conditioned media). Interestingly, breast cancer cells alone in macrophage conditioned media did not show an increase in proliferation. This shows that macrophages may not affect breast cancer proliferation directly, as all three cell types are needed for increased proliferation of breast cancer cells. Introducing macrophages into this crosstalk also resulted in increased migration abilities. After 24 hours, breast cancer cells grown in experimental co-culture migrated further to close a wound than breast cancer cells grown in control co-culture. These results show that macrophages can affect adipocyte-breast cancer cell crosstalk. This may help explain why obese breast cancer patients have worse prognosis than non-obese breast cancer patients. Further investigation into these effects may identify targets to improve prognosis and abate breast cancer aggressiveness in obese breast cancer patients. Citation Format: Vallega KA, Sang Q-XA. Disrupting interactions between human breast cancer cells, adipocytes, and macrophages [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-01-18.
PHENOTYPING LEFT HEART DISEASES OF DIFFERENT ORIGIN THROUGH AN ANALYSIS OF EXERCISE VENTILATORY AND WEBER CLASSIFICATIONS: A COMPARATIVE CASE CONTROL ANALYSIS
Authors: Tadafumi Sugimoto, Francesco Bandera, Greta Generati, Eleonora Alfonzetti, Vincenzo Tufaro, Marco Guazzi
Journal: Journal of the American College of Cardiology (2018)
Interferon-β induced in female genital epithelium by HIV-1 glycoprotein 120 via Toll-like-receptor 2 pathway acts to protect the mucosal barrier
Authors: Aisha Nazli, Sara Dizzell, Muhammad Atif Zahoor, Victor H Ferreira, Jessica Kafka, Matthew William Woods, Michel Ouellet, Ali A Ashkar, Michel J Tremblay, Dawn ME Bowdish, Charu Kaushic
Journal: Cellular and Molecular Immunology (2018)

More than 40% of HIV infections occur via female reproductive tract (FRT) through heterosexual transmission. Epithelial cells that line the female genital mucosa are the first line of defense against HIV-1 and other sexually transmitted pathogens. These sentient cells recognize and respond to external stimuli by induction of a range of carefully balanced innate immune responses. Previously, we have shown that in response to HIV-1 gp120, the genital epithelial cells (GECs) from upper reproductive tract induce an inflammatory response that may facilitate HIV-1 translocation and infection. In this study, we report that the endometrial and endocervical GECs simultaneously induce biologically active interferon-β (IFNβ) antiviral responses following exposure to HIV-1 that act to protect the epithelial tight junction barrier. The innate antiviral response was directly induced by HIV-1 envelope glycoprotein gp120 and addition of gp120 neutralizing antibody inhibited IFNβ production. Interferon-β was induced by gp120 in upper GECs through Toll-like receptor 2 signaling and required presence of heparan sulfate on epithelial cell surface. The induction of IFNβ was dependent upon activation of transcription factor IRF3 (interferon regulatory factor 3). The IFNβ was biologically active, had a protective effect on epithelial tight junction barrier and was able to inhibit HIV-1 infection in TZM-bl indicator cells and HIV-1 replication in T cells. This is the first report that recognition of HIV-1 by upper GECs leads to induction of innate antiviral pathways. This could explain the overall low infectivity of HIV-1 in the FRT and could be exploited for HIV-1 prophylaxis.
Facial plastic surgery course
Authors: Sameer Gujral
Journal: BMJ (2011)

The facial plastic surgery course is held over three days at St Mary’s Hospital in London. The faculty is made up primarily of London based consultants in ear, nose, and throat surgery, in plastic surgery, and in dermatology and invited international guest speakers. The course organiser is Kalpesh Patel (consultant ear, nose, and throat and facial plastic surgeon at Imperial College Healthcare NHS Trust). The course gives a grounding in facial anatomy and aims to familiarise delegates with surgical dermatology; local flaps for the face; rhinoplasty; otoplasty; the ageing face and rejuvenation; and relevant cosmetic procedures and techniques, including the use of botulinum toxin (Botox).

The course is aimed at trainees in ear, nose, and throat surgery, plastic surgery, and maxillofacial surgery. It is also relevant to consultants with an interest in facial plastic surgery, to dentists, and to general practitioners with an interest in facial aesthetics procedures. Trainees were …
Perioperative nutrition status of radical cystectomy patients.
Authors: Meredith Metcalf, Jill Hamilton-Reeves, Martin DeRuyter, David Bishop, Lauren Hand, Jeffrey M. Holzbeierlein, Eugene Lee
Journal: Journal of Clinical Oncology (2018)

517 Background: Radical cystectomy patients are a vulnerable population, with up to 65% suffering complications and 26% readmitted within 90 days. Patients with aggressive bladder cancer are at high risk for malnutrition. Furthermore, malnutrition is a recognized risk factor for poorer outcomes following radical cystectomy. Unclear is the longitudinal assessment of malnutrition during the entire perioperative time frame of the radical cystectomy. Methods: We initiated a prospective, feasibility pilot trial (NCT NCT02942121) evaluating the usage of a healthcare application in the perioperative management of patients undergoing radical cystectomy. As a secondary aim of this prospective trial, we evaluated the perioperative malnutrition status of each participant using the validated Patient-Generated Subjective Global Assessment (PG-SGA). This assessment was administered by registered dieticians at baseline prior to radical cystectomy and at postoperative visits: 2 week, 6 weeks, and 12 weeks. No nutrition interventions occurred during the course of the trial in order to evaluate the natural longitudinal nutritional status of this patient population. Results: Enrollment has been completed with twenty patients. Thus far, 18 patients have completed baseline PG-SGA evaluation: 13 (72%) patients were well nourished, 3 (17%) had moderate malnutrition, and 2 (11%) were severely malnourished. 11 participants have completed their 2 week visit with all but one having decrease in their PG-SGA score. Interestingly, all six patients who have completed the 12 week visit have returned to their baseline rating of the PG-SGA score. Conclusions: Patients undergoing radical cystectomy for bladder cancer are already at risk for malnutrition, which is exacerbated post-operatively. The recovery to baseline is a slow process and may be a window for impactful nutritional interventions designed to lessen the burden of surgery. Clinical trial information: NCT02942121. [Table: see text]
Abstract P1-06-12: Optimizing the use of oncotype Dx in early breast cancer
Authors: R Ruiz, F Namuche, C Flores, A Aguilar, HL Gomez
Journal: Cancer Research (2018)

Abstract Background: Oncotype Dx (ODX) prognosticates the risk of recurrence and predicts the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). However, its cost makes it prohibitive for many health care systems. Our objective was to develop a model that uses routine clinical and pathological parameters to identify ODX high risk patients which require adjuvant chemotherapy. Methods: We retrospectively reviewed ODX and pathology reports from 190 early BC patients treated between 2014 and 2016 in a specialized cancer center. Our population was divided into a training (n:133) and validation set (n:57). In the training set, among available clinico-pathological variables (age, T, ER, PR, Ki67, Elston-Ellis grade) a multiple linear regression model was carried out to select those significantly associated with ODX. Coefficients of statistically significant variables were used to build an equation. The equation was applied in the training set. These results were confronted to ODX categories. The best threshold for selecting high risk patients was identified in the training set and tested in the validation set. Results: Among the tested variables, tumor size (pT), progesterone receptor (PR), Ki67 and Ellston-Ellis grade were significantly associated with ODX RS (Table 1). The linear predictor is: (0.2544 x pT) – (0.0739 x PR) + (0.0861 x Ki67) + (5.4232 x Elston grade). The threshold score for this equation was set on 14 to discriminate high from low-intermediate risk patients. The test was able to correctly classify high risk patients with a sensitivity of 78%, a specificity of 72% and a negative predictive value of 98%. Conclusion: With further refinement ODX could be omitted in patients classified as high risk by our predictor therefore restricting and optimizing the use of ODX to a smaller population of patients. The observed ODX distribution in our patients is similar to previously reported series suggesting that this equation could be informative in similar clinical settings. Additional external testing using new datasets is ongoing. Citation Format: Ruiz R, Namuche F, Flores C, Aguilar A, Gomez HL. Optimizing the use of oncotype Dx in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-12.
Doctors should raise concerns without risking careers, BMA says
Authors: Abi Rimmer
Journal: BMJ (2016)

Doctors must be allowed to raise concerns about potential system failures without risking harm to their careers, said the BMA.

Delegates at the BMA’s annual representatives meeting in Belfast passed a motion on 20 June calling on NHS bodies to “take ownership of concerns raised by doctors about potential high profile system failures.” The BMA said that NHS bodies should do this “without exposing those doctors to career risk or other detriment.”

Proposing …
NON-INVASIVE VERSUS INVASIVE MANAGEMENT IN PATIENTS WITH PRIOR CORONARY ARTERY BYPASS SURGERY WITH A NON-ST SEGMENT ELEVATION ACUTE CORONARY SYNDROME: COMPARISONS BETWEEN THE RANDOMIZED CONTROLLED PILOT TRIAL AND REGISTRY
Authors: Matthew M.Y. Lee, Mark Petrie, Paul Rocchiccioli, Joanne Simpson, Colette Jackson, Ammani Brown, David Corcoran, Kenneth Mangion, Pio Cialdella, Novalia Sidik, Margaret McEntegart, Aadil Shaukat, Alan Rae, Stuart Hood, Eileen Peat, Iain Findlay, Clare Murphy, Alistair Cormack, Nikolay Bukov, Kanarath Balachandran, Ian Ford, Olivia Wu, Alex McConnachie, Sarah Barry, Colin Berry
Journal: Journal of the American College of Cardiology (2018)
Acute Fatty Liver of Pregnancy<sup>1</sup>
Authors: W M Hague, D W Fenton, S L B Duncan, D N Slater
Journal: Journal of the Royal Society of Medicine (1983)

Six further cases of acute fatty liver of pregnancy are presented and discussed in relation to the world literature on this rare disease of pregnancy, the aetiology of which is still unknown. The importance of vomiting in late pregnancy is emphasized. A common feature seems to be a metabolic stress, possibly related to infection, which tips a susceptible liver into metabolic failure.
POSITIVE DYNAMICS OF ENDOTHELIAL FUNCTION IN PATIENTS WITH ST SEGMENT ELEVATION MI IS ASSOCIATED WITH LDL CHOLESTEROL TARGET LEVEL ACHIEVEMENT
Authors: Oleksandr Shumakov, Alexander Parkhomenko, Anton Stepura, Oleg Irkin, Yaroslav Lutay, Dmitry Biliy, Sergey Kushnir
Journal: Journal of the American College of Cardiology (2018)
More than half of junior doctors work more than their scheduled hours
Authors: Helen Jaques
Journal: BMJ (2013)

More than half of UK trainee doctors regularly work longer than their scheduled hours, a GMC survey has found.

Over 50 000 doctors in training completed the GMC’s national training survey, and 59% of respondents said that they regularly worked longer than their scheduled hours. A third (29%) said that they never did so. 

Nearly half of respondents said that their workload intensity was heavy or very heavy in the day (43%) and at night (46%). A fifth (22%) said that they …
Laminin-521 Protein Therapy for Glomerular Basement Membrane and Podocyte Abnormalities in a Model of Pierson Syndrome
Authors: Meei-Hua Lin, Joseph B. Miller, Yamato Kikkawa, Hani Y. Suleiman, Karl Tryggvason, Bradley L. Hodges, Jeffrey H. Miner
Journal: Journal of the American Society of Nephrology (2018)

Background Laminin α 5 β 2 γ 1 (LM-521) is a major component of the GBM. Mutations in LAMB2 that prevent LM-521 synthesis and/or secretion cause Pierson syndrome, a rare congenital nephrotic syndrome with diffuse mesangial sclerosis and ocular and neurologic defects. Because the GBM is uniquely accessible to plasma, which permeates endothelial cell fenestrae, we hypothesized that intravenous delivery of LM-521 could replace the missing LM-521 in the GBM of Lamb2 mutant mice and restore glomerular permselectivity. Methods We injected human LM-521 (hLM-521), a macromolecule of approximately 800 kD, into the retro-orbital sinus of Lamb2 −/− pups daily. Deposition of hLM-521 into the GBM was investigated by fluorescence microscopy. We assayed the effects of hLM-521 on glomerular permselectivity by urinalysis and the effects on podocytes by desmin immunostaining and ultrastructural analysis of podocyte architecture. Results Injected hLM-521 rapidly and stably accumulated in the GBM of all glomeruli. Super-resolution imaging showed that hLM-521 accumulated in the correct orientation in the GBM, primarily on the endothelial aspect. Treatment with hLM-521 greatly reduced the expression of the podocyte injury marker desmin and attenuated the foot process effacement observed in untreated pups. Moreover, treatment with hLM-521 delayed the onset of proteinuria but did not prevent nephrotic syndrome, perhaps due to its absence from the podocyte aspect of the GBM. Conclusions These studies show that GBM composition and function can be altered in vivo via vascular delivery of even very large proteins, which may advance therapeutic options for patients with abnormal GBM composition, whether genetic or acquired.
Real world outcomes of upfront docetaxel for hormone naïve metastatic prostate cancer in an ethnically diverse inner-city population.
Authors: Surabhi Pathak, Romy Jose Thekkekara, Ahmed T Ahmed, Udit Yadav, Michael Russell Mullane, Kumar Kunnal Batra, Thomas E. Lad, Sarah P Psutka
Journal: Journal of Clinical Oncology (2018)

359 Background: Upfront docetaxel (UD) in castration-sensitive metastatic prostate cancer (CSPC) has improved failure-free and overall survival in the CHAARTED, GETUG-AFU 15 and STAMPEDE trials, resulting in a paradigm shift in practice patterns. However, the impact of docetaxel-based chemotherapy regimens in minorities and in real-world practice remains to be described. The objective of this study is to evaluate tolerability and response to UD in an inner-city ethnically diverse CSPC cohort. Methods: We retrospectively reviewed clinical data for CSPC patients at Cook County Hospital. Patients treated with UD and androgen deprivation (UD, n = 49, 2013-17) were compared to those receiving androgen deprivation alone (ADT, n = 42, 2010-17) using descriptive statistics and Cox Proportional Hazards analysis. Results: Median age was 59 and 60 years in UD and ADT, respectively. African Americans, Hispanics and Caucasians formed 69%, 18%, and 10% in UD and 64%, 9.5% and 26% in ADT. Median PSA at diagnosis was: UD 536 [72-1110] ng/ml, ADT 229 [54-999] ng/ml (p = 0.3). Gleason score &gt; 7 was present in 89.8% [UD] and 92.8% [ADT]. UD and ADT had similar frequency of bone (91% vs. 95%, p = 0.5), visceral (12.2% vs. 11.9%, p = 0.9) and retroperitoneal nodal metastases (55% vs. 45.2%, p = 0.3). UD was initiated a median of 8 weeks from diagnosis. 94% in UD received &gt; 3 cycles of chemotherapy. CTCAE grade &gt; 3 events included anemia (6%); neutropenia (6%); infection (4%); diarrhea (4%); peripheral neuropathy (6%), and fatigue (2%). Median PSA nadir was 3.2 [0.5-40.1] vs. 3.45 [0.1-36.4] ng/ml and time to nadir was 20 [13-27] vs. 41 [19-69] weeks in UD vs. ADT. Biochemical progression was observed in 34.7% [UD] vs. 40.5% [ADT]. Median time to castration-resistance was UD: 39 [31-67] vs. ADT: 65 [34-76] weeks [HR: 0.9; 95% CI 0.4-1.8; p = 0.7]. There were 12 deaths [UD: 4; ADT: 8] during a median follow-up of 46 [23-86, UD] and 111 [68-157, ADT] weeks. Conclusions: In a diverse underserved population with CSPC, UD was well tolerated but was not associated with improvement in time to castration compared to ADT. These results warrant validation and underscore the importance of ensuring accrual of minorities in clinical trials.