tbuckley/cabot-search huggingface dataset:
Significance of serum buttyrylcholinesterase level before chemotherapy as an independent predictor of overall survival in patients with metastatic upper-tract urothelial cancer.
Authors: Takahiro Yoneyama, Hirotake Kodama, Shogo Hosogoe, Ayumu Kusaka, Noriko Tokui, Tohru Yoneyama, Atsushi Imai, Hayato Yamamoto, Shingo Hatakeyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2018)

486 Background: Systemic inflammation is a common host reaction to cancer progression. Serum level of buttyrylcholinesterase (BChE) have been reported to reflect the presence of inflammation and other clinical conditions. BChE is an alphaglycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, injury, infection, and malignant disease. We retrospectively evaluated the potential prognostic significance of buttyrylcholinesterase before chemotherapy as an independent predictor of overall survival in patients with advanced upper-tract urothelial cancer. Methods: We treated seventy-four patients (52 men and 22 women) with advanced upper-tract urothelial cancer (UTUC) at our clinic between August 2004 and September 2017. The average age was 69.3 (43–89), and average eGFR was 50.5 (11.6–99.3) ml/minute/1.73m 2 . Mean observation period was 28.7 (3–111) months. Levels of serum BChE (normal range 168-470 U/L) were measured 1 week before chemotherapy. The average serum level of BChE were 240.6 U/L (53-509). The patients received 2 courses of GCarbo consisted of 800mg/m 2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCcarbo was performed. If this regimen did not induce any tumor size reduction, we switched to 2 courses of GCarboD (D; 70mg/m 2 ) treatment as second-line treatment. Results: GCarbo regimen yielded 5 cases (6.8%) of CR, 32 (43.2%) of PR, and the average duration of response of 11.4 (2–29) months. GCarboD treatment was administered in 21 cases, and yielded 2 (9.5%) PR and a duration of response was 31.5(7-50) months. The median over-all survival period was 14.3 months. When analyzed by serum BChE level, the ovearall survival were 22.0 months in the BChE &gt; 168 U/L group and 11.0 months in the BChE &lt; 168 group (p = 0.0035). The level of serum BChE showed no association with treatment effect. Conclusions: Serum BChE level before chemotherapy may have the potential to predict overall survival in patients with advanced upper-tract urothelial cancer.
Author Correction: Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation
Authors: Sebastian Preissl, Rongxin Fang, Hui Huang, Yuan Zhao, Ramya Raviram, David U. Gorkin, Yanxiao Zhang, Brandon C. Sos, Veena Afzal, Diane E. Dickel, Samantha Kuan, Axel Visel, Len A. Pennacchio, Kun Zhang, Bing Ren
Journal: Nature Neuroscience (2018)
Detection of prostate cancer lesions using Gallium-68 PSMA-11 PET in men with biochemical recurrence following radical prostatectomy.
Authors: Adam J. Gadzinski, Kirsten L Greene, Peter Carroll, Charles J. Ryan, Felix Y Feng, Tom Hope
Journal: Journal of Clinical Oncology (2018)

236 Background: Conventional imaging techniques infrequently detect the site of prostate cancer disease in men with biochemical recurrence following radical prostatectomy (RP). We examine the use of Gallium-68 Prostate-Specific Membrane Antigen (PSMA) positron emission tomography (PET) to determine the site of disease recurrence in these men. Methods: We retrospectively reviewed men with persistently detectable prostate specific antigen (PSA) and those with formal biochemical recurrence (PSA ≥ 0.2 ng/mL) following RP who underwent PSMA PET scan under our institution's prospective trials (NCT02918357 &amp; NCT02611882). We assessed the location of detected recurrences, and examined the distribution of recurrence location (prostate bed, pelvic lymph nodes (LN), and extra-pelvic disease) according to PSA at time of PET scan. Results: One hundred and fifty-eight men underwent PSMA PET after RP, 46% of men had previously undergone either adjuvant or salvage radiation therapy. Eleven men (7%) had the scan for persistently detectable PSA &lt; 0.2 and 93% of men had biochemical recurrence. At time of RP, 66% of men had ≥pT3a disease, 40% had positive surgical margins, and 18% had positive lymph nodes. Gleason grade at RP was ≤3+3 in 5% of men, 3+4 in 27%, 4+3 in 32% and ≥4+4 in 36%. Overall, 77% of men had a lesion detectable on PSMA PET. Men with higher PSA at time of scan had a higher prevalence of lesions, with all men PSA &gt; 6.0 having at least one lesion on PSMA PET (Table). Overall, we found extra-pelvic lesions in 44% of all men, and 58% of men with PSA ≥ 1.0. These are areas not typically covered by salvage radiation fields. Conclusions: PSMA PET detects lesions in a high proportion of men with biochemical recurrence following RP, with many lesions outside of the pelvis. This may facilitate more precise targeting of treatment areas for these patients. Clinical trial information: NCT02918357. Clinical trial information: NCT02611882. [Table: see text]
Free online content for doctors and patients
Authors: Umar Sadat
Journal: BMJ (2006)

This website, developed by Flying Publisher, provides links to 650 books, which are listed in alphabetical order in a variety of specialties in English, German, Portuguese, Italian, and other languages. The interface is user friendly and provides access to links for free journals, websites, and the HIV medicine site from the home page. The user can also subscribe for free to journal alerts. The website promotes availability of free online medical literature by encouraging writers to publish their own …
Lysosomal Cholesterol Hydrolysis Couples Efferocytosis to Anti-Inflammatory Oxysterol Production
Authors: Manon Viaud, Stoyan Ivanov, Nemanja Vujic, Madalina Duta-Mare, Lazaro-Emilio Aira, Thibault Barouillet, Elsa Garcia, Francois Orange, Isabelle Dugail, Isabelle Hainault, Christian Stehlik, Sandrine Marchetti, Laurent Boyer, Rodolphe Guinamard, Fabienne Foufelle, Andrea Bochem, Kees G. Hovingh, Edward B. Thorp, Emmanuel L. Gautier, Dagmar Kratky, Paul Dasilva-Jardine, Laurent Yvan-Charvet
Journal: Circulation Research (2018)

Macrophages face a substantial amount of cholesterol after the ingestion of apoptotic cells, and the LIPA (lysosomal acid lipase) has a major role in hydrolyzing cholesteryl esters in the endocytic compartment.Here, we directly investigated the role of LIPA-mediated clearance of apoptotic cells both in vitro and in vivo.We show that LIPA inhibition causes a defective efferocytic response because of impaired generation of 25-hydroxycholesterol and 27-hydroxycholesterol. Reduced synthesis of 25-hydroxycholesterol after LIPA inhibition contributed to defective mitochondria-associated membrane leading to mitochondrial oxidative stress-induced NLRP3 (NOD-like receptor family, pyrin domain containing) inflammasome activation and caspase-1-dependent Rac1 (Ras-related C3 botulinum toxin substrate 1) degradation. A secondary event consisting of failure to appropriately activate liver X receptor-mediated pathways led to mitigation of cholesterol efflux and apoptotic cell clearance. In mice, LIPA inhibition caused defective clearance of apoptotic lymphocytes and stressed erythrocytes by hepatic and splenic macrophages, culminating in splenomegaly and splenic iron accumulation under hypercholesterolemia.Our findings position lysosomal cholesterol hydrolysis as a critical process that prevents metabolic inflammation by enabling efficient macrophage apoptotic cell clearance.
My son has been offered a place to study medicine at Cambridge and at University College London. Which should he choose and where are the best opportunities for postgraduate training?
Authors: Brian Angus
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>
All HEE staff are offered redundancy
Authors: Abi Rimmer
Journal: BMJ (2017)

All staff at Health Education England have been offered the chance to take voluntary redundancy.

On Thursday 23 February HEE, the organisation responsible for medical education and training in England, wrote to all its 2614 staff announcing that it had opened a “Volunteering for Redundancy Scheme” to allow them to say whether they would be prepared to volunteer for redundancy.

In 2014 HEE announced that it was consulting on substantial changes designed to ensure its sustainability, reduce its senior staffing bill, and cut its running costs. …
Potentially curable gastric adenocarcinoma (GAC) patients treated without surgery.
Authors: Dilsa Mizrak Kaya, Graciela M. Nogueras-Gonzalez, Jeannelyn Estrella, Kazuto Harada, Fatemeh Ghazanfari Amlashi, Quan Lin, Mariela A. Blum Murphy, Jeffrey H Lee, Brian Weston, Manoop S. Bhutani, Aurelio Matamoros, Tara L. Sagebiel, Catherine E Devine, Madhavi Patnana, Bruce D. Minsky, Prajnan Das, Brian D. Badgwell, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2018)

120 Background: Surgery is the best option to cure localized GAC. When surgery is not possible due to comorbidities or patient refusal, definitive chemoradiation is an option. We report on one of the largest cohorts of GAC patients who did not have surgery. Methods: We identified 71 patients with localized GAC who received chemo/chemoradiation therapy but did not have surgery. We assessed various endpoints (overall survival [OS] and recurrence-free survival [RFS]). Clinical complete response (cCR; negative post therapy biopsy and no evidence of cancer by imaging) was also assessed. Results: The median follow-up time was 1.8 years (range; 0.4-10.6). Most of the patients were men (64.8%) and the median age was 73 years (range; 30-96). Reason for not having surgery included comorbidities in 34 (47.9%), poor performance status 14 (19.7%), and patient refusal 23 (32.4%). Most of the patients (80.3%) received chemoradiation and 14 (19.7%) could receive only chemotherapy. Of all 71 patients, 32 (45.1%) achieved to a cCR. For the entire cohort, the median OS was 2.1 years (95% Cl 0.98-1.02). The estimated OS rates at 2 and 5 years were 46.5% and 11.3%, respectively. The median OS and the median RFS for patients with cCR were 2.3 and 1.8 years (95% Cl 0.97-1.01), respectively. Female gender (HR 0.47, 95% Cl 0.25-0.91, p = 0.024) and chemoradiation (HR 0.36, 95% Cl 0.16-0.85; p = 0.019) were independently associated with longer OS in the multivariate analysis. Histologic grade and the presence of signet ring cell had no effect on OS. Conclusions: Our data show that patients with localized GAC who do not undergo surgery have a low but measurable 5-year OS rate of 11.3%.
If I am contracted to do 1:8 weekend, can my trust change it to 1:7? Where do I stand legally?
Authors: David Adsett
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>
Post-abortion contraceptive acceptance and choice among women receiving abortion care at Saint Paul's Hospital, Addis Ababa, Ethiopia: a cross-sectional study
Authors: Matiyas Asrat, Delayehu Bekele, Sarah D Rominski
Journal: The Lancet Global Health (2018)

BackgroundAn exploration and comparison of the characteristics and choices of women who did and did not accept post-abortion contraception would help to provide recommendations for more effective and appropriate contraceptive counselling and services. We aimed to determine the contraceptive acceptance rate and factors associated with choice of contraception, in particular modern and long-acting methods, in women after an abortion at a hospital in Addis Ababa, Ethiopia.MethodsWe did a cross-sectional study at Saint Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia, with women who received abortion care services for induced or spontaneous abortions from January to June, 2015. Logistic regression was used to determine factors associated with acceptance and choice of method of contraceptives.Findings552 women were included in the study. 478 had spontaneous abortions and 74 had induced abortions. 500 (91%) of them adopted modern contraception post-abortion and 103 (19%) received long-acting reversible contraceptives (LARC). Multivariable analysis showed that being a housewife (adjusted odds ratio [aOR] 3·43, 95% CI 1·20–9·80), being married (3·31, 1·41–7·74), and parity greater than 1 (2·70, 1·04–7·03) had a significant association with the odds of adopting any modern method of contraception after abortion. Adoption of LARC was positively associated with being a student (4·62, 1·50–14·22), parity greater than 1 (2·21, 1·12–4·36), and induced abortion (2·91, 1·46–5·80).InterpretationThe post-abortion contraceptive acceptance rate was higher than other studies done in Ethiopia. However, there should be increased advocacy and multipronged activities by the hospital and federal Ministry of Health to further increase the acceptance of LARC post abortion. Further research to assess follow-up discontinuation rates of contraceptive methods after discharge is an important next step.FundingSaint Paul's Hospital Millennium Medical College.
Regeneration of Cochlear Hair Cells and Hearing Recovery through Hes1 Modulation with siRNA Nanoparticles in Adult Guinea Pigs
Authors: Xiaoping Du, Qunfeng Cai, Matthew B. West, Ibrahima Youm, Xiangping Huang, Wei Li, Weihua Cheng, Don Nakmali, Donald L. Ewert, Richard D. Kopke
Journal: Molecular Therapy (2018)

Deafness is commonly caused by the irreversible loss of mammalian cochlear hair cells (HCs) due to noise trauma, toxins, or infections. We previously demonstrated that small interfering RNAs (siRNAs) directed against the Notch pathway gene, hairy and enhancer of split 1 (Hes1), encapsulated within biocompatible poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) could regenerate HCs within ototoxin-ablated murine organotypic cultures. In the present study, we delivered this sustained-release formulation of Hes1 siRNA (siHes1) into the cochleae of noise-injured adult guinea pigs. Auditory functional recovery was measured by serial auditory brainstem responses over a nine-week follow-up period, and HC regeneration was evaluated by immunohistological evaluations and scanning electron microscopy. Significant HC restoration and hearing recovery were observed across a broad tonotopic range in ears treated with siHes1 NPs, beginning at three weeks and extending out to nine weeks post-treatment. Moreover, both ectopic and immature HCs were uniquely observed in noise-injured cochleae treated with siHes1 NPs, consistent with de novo HC production. Our results indicate that durable cochlear HCs were regenerated and promoted significant hearing recovery in adult guinea pigs through reversible modulation of Hes1 expression. Therefore, PLGA-NP-mediated delivery of siHes1 to the cochlea represents a promising pharmacologic approach to regenerate functional and sustainable mammalian HCs in vivo.
Effective teaching skills—how to become a better medical educator
Authors: Shvaita Ralhan, Paul Bhogal, Gauraang Bhatnagar, Jane Young, Matt Green
Journal: BMJ (2012)

<b>Shvaita Ralhan</b>, <b>Paul Bhogal</b>, <b>Gauraang Bhatnagar</b>, <b>Jane Young</b>, and <b>Matt Green</b>, authors of <i>Effective Medical Teaching Skills</i>, explore the importance of teaching in modern medicine and what steps you can take to enhance your teaching skills
Aryl hydrocarbon receptor signaling promotes ORMDL3-dependent generation of sphingosine-1-phosphate by inhibiting sphingosine-1-phosphate lyase
Authors: Hsueh-Chun Wang, Tzu-Hsuan Wong, Li-Ting Wang, Hsiang-Han Su, Hsiu-Yueh Yu, Ai-Hsuan Wu, Yu-Chun Lin, Hua-Ling Chen, Jau-Ling Suen, Shih-Hsien Hsu, Li-Chen Chen, Yufeng Zhou, Shau-Ku Huang
Journal: Cellular and Molecular Immunology (2018)
Comparison of Observed Harms and Expected Mortality Benefit for Persons in the Veterans Health Affairs Lung Cancer Screening Demonstration Project
Authors: Tanner J. Caverly, Angela Fagerlin, Renda Soylemez Wiener, Christopher G. Slatore, Nichole T. Tanner, Shira Yun, Rodney Hayward
Journal: JAMA Internal Medicine (2018)

Our study used self-reported, cross-sectional data without a comparison group of individuals enrolled in traditional plans.To identify HDHP enrollees, we relied on participants' knowledge of their deductible, because verification of insurance benefits was infeasible.Respondents were sampled from an internet survey panel and may have had different consumer characteristics than nonrespondents.There are a number of ways in which consumer behaviors could be encouraged among and made more helpful to individuals enrolled in HDHPs.Providers could help patients anticipate services that they may need in the future so that patients can try to save for them.Health systems could make prices for services available at the point of care to facilitate patient and clinician conversations about cost.Employers and insurers could go beyond disseminating price information to help patients learn how to use this information in health care decisions.Such efforts will become increasingly important as enrollment in HDHPs continues to increase and could become essential if modifications to the structure or implementation of the Affordable Care Act accelerate patients' exposure to high cost sharing.
Premier league doctor
Authors: Sara Kelly
Journal: BMJ (2004)

Background: Previous studies have shown activity against viruses, bacteria, inflammation and oral lichenoid dysplasia of alkaline extract of the leaves of Sasa senanensis Rehder (SE), suggesting its possible application to oral diseases. In the present study, we performed a small-scale clinical test to investigate whether SE is effective against halitosis and in oral bacterial reduction. Materials and Methods: A total of 12 volunteers participated in this study. They brushed their teeth immediately after meals three times each day with SE-containing toothpaste (SETP) or placebo toothpaste. Halitosis in the breath and bacterial number on the tongue were measured by commercially available portable apparatuses at a specified time in the morning. Results: Some relationship was observed between halitosis and bacterial number from each individual, especially when those with severe halitosis were included. Repeated experiments demonstrated that SETP significantly reduced halitosis but not the bacterial number on the tongue. Conclusion: The present study provides for the first time the basis for anti-halitosis activity of SE.
High PIM1 expression is a biomarker of T-cell acute lymphoblastic leukemia with JAK/STAT activation or t(6;7)(p21;q34)/TRB@-PIM1 rearrangement
Authors: Roberta La Starza, Monica Messina, Valentina Gianfelici, Valentina Pierini, Caterina Matteucci, Tiziana Pierini, Maria Zaira Limongi, Antonella Vitale, Giovanni Roti, Sabina Chiaretti, Robin Foà, Cristina Mecucci
Journal: Leukemia (2018)
Highland surgical boot camp—an apprenticeship in a week
Authors: Katharine Hamlin, David Finlayson
Journal: BMJ (2012)

Surgical training has changed: the apprenticeship model of training is dead, but what has taken its place? NHS Highland has developed the Highland surgical boot camp to help tackle this challenge.

The boot camp is aimed at trainees at the beginning of their careers: early years specialty or core trainees and surgically minded foundation doctors. My course had nine participants from foundation year 1 to core training year 2.

The excellent new Centre for Health Sciences at Raigmore Hospital in Inverness is a new facility with state of the art wet labs, clinical simulators, and a mock ward.

The course was developed and is led by the general surgeons Angus Watson and Kenneth …
MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD
Authors: Hannah Major-Monfried, Anne S. Renteria, Attaphol Pawarode, Pavan Reddy, Francis Ayuk, Ernst Holler, Yvonne A. Efebera, William J. Hogan, Matthias Wölfl, Muna Qayed, Elizabeth O. Hexner, Kitsada Wudhikarn, Rainer Ordemann, Rachel Young, Jay Shah, Matthew J. Hartwell, Mohammed S. Chaudhry, Mina Aziz, Aaron Etra, Gregory A. Yanik, Nicolaus Kröger, Daniela Weber, Yi-Bin Chen, Ryotaro Nakamura, Wolf Rösler, Carrie L. Kitko, Andrew C. Harris, Michael Pulsipher, Ran Reshef, Steven Kowalyk, George Morales, Ivan Torres, Umut Özbek, James L. M. Ferrara, John E. Levine
Journal: Blood (2018)
Doctors must pursue quality improvement despite challenges, King’s Fund says
Authors: Matthew Limb
Journal: BMJ (2015)

Doctors should pursue schemes to improve the quality of care, however hardpressed and lacking in resources they think they are, says Vijaya Nath, director of leadership development at the think tank the King’s Fund. 

Speaking at a debate held at the King’s Fund, Nath told leading clinicians that doctors who feared that NHS trusts were paying “lip service” to quality improvement while cutting back vital posts should continue to drive forward innovations. 

“If clinical leaders don’t engage in the process of quality improvement [QI] and don’t keep talking about it and asking for it, who will? Now, in times of scarcity, is exactly the wrong time to disinvest in developing the talent of people in QI,” she said.

Nath hosted an event on 23 September on the topic of achieving medical engagement through quality improvement. She said that strong medical leadership was vital to organisations’ efforts to improve the safety of patients and the quality of care and to the delivery of long lasting benefits to patients. But the NHS was unlikely to see a nationally funded quality improvement scheme, she said.

She told her audience of around 40 clinicians, “You can’t wait for a national programme. You have to go out there and do something with what you can do. You have to focus on the 20% of the things that will give you a bigger impact, not the whole 100%.”

Health experts increasingly look to the United States for evidence on improving care quality, she said, and the event …