tbuckley/cabot-search huggingface dataset:
<i>IKZF1</i><sup>plus</sup>Defines a New Minimal Residual Disease–Dependent Very-Poor Prognostic Profile in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Martin Stanulla, Elif Dagdan, Marketa Zaliova, Anja Möricke, Chiara Palmi, Giovanni Cazzaniga, Cornelia Eckert, Geertruy te Kronnie, Jean-Pierre Bourquin, Beat Bornhauser, Rolf Koehler, Claus R. Bartram, Wolf-Dieter Ludwig, Kirsten Bleckmann, Stefanie Groeneveld-Krentz, Denis Schewe, Stefanie V. Junk, Laura Hinze, Norman Klein, Christian P. Kratz, Andrea Biondi, Arndt Borkhardt, Andreas Kulozik, Martina U. Muckenthaler, Giuseppe Basso, Maria Grazia Valsecchi, Shai Izraeli, Britt-Sabina Petersen, Andre Franke, Petra Dörge, Doris Steinemann, Oskar A. Haas, Renate Panzer-Grümayer, Hélène Cavé, Richard S. Houlston, Gunnar Cario, Martin Schrappe, Martin Zimmermann
Journal: Journal of Clinical Oncology (2018)

Purpose Somatic deletions that affect the lymphoid transcription factor–coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions. Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica–Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22.33/Yp11.31 (PAR1 region; CRLF2, CSF2RA, and IL3RA), and ERG; replication of findings involved 417 patients from the same trial. Results IKZF1 deletions that co-occurred with deletions in CDKN2A, CDKN2B, PAX5, or PAR1 in the absence of ERG deletion conferred the worst outcome and, consequently, were grouped as IKZF1 plus . The IKZF1 plus group comprised 6% of patients with BCP ALL, with a 5-year event-free survival of 53 ± 6% compared with 79 ± 5% in patients with IKZF1 deletion who did not fulfill the IKZF1 plus definition and 87 ± 1% in patients who lacked an IKZF1 deletion ( P ≤ .001). Respective 5-year cumulative relapse incidence rates were 44 ± 6%, 11 ± 4%, and 10 ± 1% ( P ≤ .001). Results were confirmed in the replication cohort, and multivariable analyses demonstrated independence of IKZF1 plus . The IKZF1 plus prognostic effect differed dramatically in analyses stratified by minimal residual disease (MRD) levels after induction treatment: 5-year event-free survival for MRD standard-risk IKZF1 plus patients was 94 ± 5% versus 40 ± 10% in MRD intermediate- and 30 ± 14% in high-risk IKZF1 plus patients ( P ≤ .001). Corresponding 5-year cumulative incidence of relapse rates were 6 ± 6%, 60 ± 10%, and 60 ± 17% ( P ≤ .001). Conclusion IKZF1 plus describes a new MRD-dependent very-poor prognostic profile in BCP ALL. Because current AIEOP-BFM treatment is largely ineffective for MRD-positive IKZF1 plus patients, new experimental treatment approaches will be evaluated in our upcoming trial AIEOP-BFM ALL 2017.
The Productivity Burden of Diabetes at a Population Level
Authors: Dianna J. Magliano, Valencia J. Martin, Alice J. Owen, Ella Zomer, Danny Liew
Journal: Diabetes Care (2018)

Recent studies suggest that diabetes may impact work productivity. In the current study, we sought to estimate the lifetime and population impact of diabetes on productivity using the novel measure of "productivity-adjusted life years" (PALYs).Using age-specific mortality rates and a productivity index attributable to diabetes (akin to the quality of life index, but which adjusts for reduction in productivity) and life table modeling, we estimated years of life and PALYs lost to diabetes among Australians with diabetes currently aged 20-65 years, with follow-up until 69 years. Life tables were first constructed for the cohort with diabetes and then repeated for the same cohort but with the assumption that they no longer had diabetes. The "nondiabetic" cohort had lower mortality rates and improved productivity. The differences in total years of life lived and PALYs lived between the two cohorts reflected the impact of diabetes.Overall, diabetes reduced total years of life lived by the cohort by 190,219 years or almost 3%. Diabetes reduced PALYs by 11.6% and 10.5% among men and women, respectively. For both sexes, the impact of diabetes on productivity was lowest in those aged 65-69 years and highest in those 20-24 years. Among the latter, PALYs were reduced by 12.2% and 11.0% for men and women, respectively.Elimination of diabetes can prolong life years lived by the whole population and increase the amount of productive years lived. Employers and government should be aware that having diabetes affects work force productivity and implement prevention programs to reduce the impact of diabetes on the workforce.
Conceptually Novel Black Phosphorus/Cellulose Hydrogels as Promising Photothermal Agents for Effective Cancer Therapy
Authors: Chenyang Xing, Shiyou Chen, Meng Qiu, Xin Liang, Quan Liu, Qingshuang Zou, Zhongjun Li, Zhongjian Xie, Dou Wang, Biqin Dong, Liping Liu, Dianyuan Fan, Han Zhang
Journal: Advanced Healthcare Materials (2018)

Abstract Black phosphorus (BP) has recently emerged as an intriguing photothermal agent in photothermal therapy (PTT) against cancer by virtue of its high photothermal efficiency, biocompatibility, and biodegradability. However, naked BP is intrinsically characterized by easy oxidation (or natural degradation) and sedimentation inside the tumor microenvironment, leading to a short‐term therapeutic and inhomogeneous photothermal effect. Development of BP‐based nanocomposites for PTT against cancer therefore remains challenging. The present work demonstrates that green and injectable composite hydrogels based on cellulose and BP nanosheets (BPNSs) are of great efficiency for PTT against cancer. The resultant cellulose/BPNS‐based hydrogel possesses 3D networks with irregular micrometer‐sized pores and thin, strong cellulose‐formed walls and exhibits an excellent photothermal response, enhanced stability, and good flexibility. Importantly, this hydrogel nanoplatform is totally harmless and biocompatible both in vivo and in vitro. This work may facilitate the development of BP–polymer‐based photothermal agents in the form of hydrogels for biomedical‐related clinic applications.
Doctors without indemnity cover could have their licence removed, says GMC
Authors: Abi Rimmer
Journal: BMJ (2014)

Doctors without appropriate insurance or indemnity cover could have their licence to practise removed, the General Medical Council has said.

The GMC has proposed changes that would award it new powers to withdraw doctors’ licences if they failed to have appropriate indemnity cover for “liabilities incurred in their practice.”1 Doctors are also at risk of losing their licence if they cannot provide evidence or information that proves that they have such cover in place, the GMC said.

“The new regulations …
What help is available to retrain (or help create jobs for) doctors with chronic disabilities who cannot continue to work as medics in the NHS?
Authors: Ruth Chambers
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>
Managing the Most Precious Resource in Medicine
Authors: Graham T. McMahon
Journal: New England Journal of Medicine (2018)

Many health care institutions appear to have lost sight of the truism that our health professionals are our most precious resource. With increasing commoditization, commercialization, productivity targets, and administrative burdens, the volunteerism and soul that have typified our profession for generations are suffering. It is increasingly clear that many residents and physicians are focused on surviving rather than thriving. The residents who participated in the iCOMPARE (Individualized Comparative Effectiveness of Models Optimizing Patient Safety and Resident Education) trial,1 reported now in the Journal, may provide the clearest signal yet of the distress they feel and may also help us identify . . .
Oral and maxillofacial surgery—is it time to rethink the long training pathway?
Authors: Peter A Brennan, Velupillai Ilankovan, James S Brown, Alex Goodson, Karl Payne, Arpan Tahim, David A Koppel
Journal: BMJ (2016)

Oral and maxillofacial surgery has the longest training pathway of any medical specialty in the UK. Peter Brennan and colleagues look at ways to shorten this
T cell responses to tumor associated antigens in multiple myeloma patients treated with MV-NIS, an oncolytic measles virus.
Authors: Nandakumar Packiriswamy, Deepak Upreti, Yumei Zhou, Angela Dispenzieri, Kah Whye Peng, Stephen J. Russell
Journal: Journal of Clinical Oncology (2018)

218 Background: Evidence from mouse studies shows that Oncolytic viral mode of tumor cell killing can boost the cytotoxic T lymphocyte response against tumor associated antigens (TAA), leading to ‘bystander’ killing of uninfected tumor cells. Methods: To investigate whether oncolytic virotherapy can boost immune responses to tumor antigens in human subjects we studied T cell responses to 10 different TAA reported to have high expression in patients with multiple myeloma (n = 10) before and after intravenous administration of an oncolytic measles virus (MV-NIS). Baseline and 6 week post-therapy PBMC samples were stimulated with peptides specific to each of the selected TAA and their responses to this antigenic stimulation were measured using IFNγ ELISPOT. Results: Despite their prior exposure to multiple immunosuppressive treatment regimens, some of the tested patients had higher T cell responses to some of the TAA even prior to MV-NIS. Baseline T cell responses against MAGEc1 were present in 50% of the patients, and against hTERT and NYESO-1 in 30% of the patients. Furthermore, MV-NIS treatment significantly boosted T cell responses against NYESO-1, MAGEc1, MAGEA1 and MUC1 in 40% of the patients. Interestingly, in one outlier patient who achieved a stringent and durable complete disease remission after MV-NIS therapy, strong baseline T cell responses were present against 8 of the 10 tested TAA but did not change significantly after virotherapy. Based on the T cell responses to the TAA, three distinct phenotypes can be identified. Phenotype 1 was characterized by positive T cell responses to TAA prior and post therapy, Phenotype 2 was characterized by positive T cell responses to TAA only post therapy and phenotype 3 was characterized by negative T cell responses to TAA prior and post therapy. Conclusions: Our data suggests oncolytic measles virotherapy boosted the cytotoxic T lymphocyte response against tumor associated antigens in some of the patients. Identifying patient’s phenotype based on responsiveness to the TAA could be useful marker for identifying the immune responsive state in multiple myeloma patients and identify patients who can be most responsive to oncolytic measles virotherapy. Clinical trial information: NCT00450814.
Diverse Evolutionary Origins and Mechanisms of Lens Regeneration
Authors: Jonathan J Henry, Paul W Hamilton
Journal: Molecular Biology and Evolution (2018)

In this review, we compare and contrast the three different forms of vertebrate lens regeneration: Wolffian lens regeneration, cornea-lens regeneration, and lens regeneration from lens epithelial cells. An examination of the diverse cellular origins of these lenses, their unique phylogenetic distribution, and the underlying molecular mechanisms, suggests that these different forms of lens regeneration evolved independently and utilize neither conserved nor convergent mechanisms to regulate these processes.
Evaluation and Treatment of Hirsutism in Premenopausal Women
Authors: Mizuho S. Mimoto, Julie L. Oyler, Andrew M. Davis
Journal: JAMA (2018)

ProblemHirsutism is defined as excessive terminal (coarse) hair growth in male androgen-dependent areas and is distinguished from hypertrichosis (generalized nonsexual excessive hair growth).Hirsutism affects 5% to 10% of women worldwide and can lead to significant emotional distress and expense 1,2 involving medications, cosmetics, and hair removal procedures.Hirsutism is a clinical diagnosis based on the Ferriman-Gallwey (FG) score, which rates hair growth from 0 to 4 in 9 androgen-dependent areas.In the US general population, a normal score is less than 8; mild, 8-15; and severe, greater than 15. 1 Polycystic ovary syndrome, associated with abnormally increased androgen levels, accounts for 75% to 80% of hirsutism. 1Another 5% to 20% of cases are due to idiopathic hirsutism, which is diagnosed in the absence of increased androgen levels. 1 The remainder of cases (<5%) are due to rare but clinically important diagnoses that include nonclassic congenital adrenal hyperplasia, androgensecreting tumors, and Cushing syndrome as well as medication adverse effects.Importantly, the current guideline recognizes and recommends treating patient-important hirsutism, defined as hair growth that causes distress in the absence of an abnormal hirsutism score. 1,
The clinician-programmer: designing the future of medical practice
Authors: David Bargiela, Misha M Verkerk
Journal: BMJ (2013)

The role of clinician-programmer provides a novel opportunity for doctors in all specialties to apply their creativity to improve patient care. <b>David Bargiela</b> and <b>Misha M Verkerk</b> look at this role and explain why doctors need to be involved in the development of healthcare software
Interim Analysis of a Phase 1 Trial of SGN-CD33A in Patients with CD33-Positive Acute Myeloid Leukemia (AML)
Authors: Eytan M. Stein, Anthony Stein, Roland B. Walter, Amir T. Fathi, Jeffrey E. Lancet, Tibor J. Kovacsovics, Anjali S. Advani, Daniel J DeAngelo, Megan M. O'Meara, Baiteng Zhao, Dana A. Kennedy, Harry P. Erba
Journal: Blood (2014)
Nontoxic, double-deletion-mutant rabies viral vectors for retrograde targeting of projection neurons
Authors: Soumya Chatterjee, Heather A. Sullivan, Bryan J. MacLennan, Ran Xu, YuanYuan Hou, Thomas K. Lavin, Nicholas E. Lea, Jacob E. Michalski, Kelsey R. Babcock, Stephan Dietrich, Gillian A. Matthews, Anna Beyeler, Gwendolyn G. Calhoon, Gordon Glober, Jennifer D. Whitesell, Shenqin Yao, Ali Cetin, Julie A. Harris, Hongkui Zeng, Kay M. Tye, R. Clay Reid, Ian R. Wickersham
Journal: Nature Neuroscience (2018)
The value of skills
Authors: Tom Moberly
Journal: BMJ (2014)

At the same time as emergency medicine has to deal with the staff shortages that have resulted from long running recruitment problems, the specialty also faces a downward spiral of lost skills.

As Abi Rimmer reports (http://careers.bmj.com/careers/advice/view-article.html?id=20018602), a recent meeting heard about the impact on trainees’ skills of the constant pressure to triage, rather than treat, patients. One trainee spoke of a “self fulfilling cycle” where …
I'm interested in general practice and will start F2 in August 2005. What would I do after F2 when I finish?
Authors: Anne Hastie
Journal: BMJ (2005)

Apparently we live in the time of post-truth and alternative facts. However, we do not have to take this lying down. What we, the scientific community, can offer is a viable alternative, meaning real facts. There are two things that are critical in this: what to do when faced with outright lies or opinions parading as facts and what to offer in their place. The key to both issues is bias. Alternative facts consciously ignore biases and their effects. Somehow a personal gut feeling just trumps scientific reasoning. The best thing we can do is to accept the existence of biases and to try and minimise their effects in what we do. One way to do this is by means of systematic review. It is a means of abstracting a higher level of truth from multiple scientific studies that each examine a similar issue. Whilst synthesising their results and formulating overall conclusions, one explicitly displays the biases affecting both the existing research (what others have done) and the process of synthesis (what you do to combine the results of the studies in one conclusion). For example, a Cochrane review found high quality evidence that the use of blunt needles appreciably reduces the risk of exposure to blood and bodily fluids for surgeons and their assistants over a range of operations. High quality evidence means that the finding is not significantly affected by biases in the evidence or in the process to combine their results. Future research is unlikely to change this conclusion. Conversely another Cochrane review found very low quality evidence that bullying behaviours may be prevented in the workplace. Future research is very likely to change this conclusion. Know thyself and be open about your failings. That is a sound basis for true facts.
Internet interventions help patients newly diagnosed with cancer improve their quality of life
Authors: Ted Gansler
Journal: CA A Cancer Journal for Clinicians (2018)

Key Points Distress is very common among individuals living with cancer, and can adversely affect quality of life and decrease adherence to treatment regimens. All individuals diagnosed with cancer should be evaluated for distress and treated according to guideline recommendations. Many individuals with cancer‐related distress remain undiagnosed and untreated. Web‐based psychosocial interventions may provide a valuable option for some patients facing access barriers to face‐to‐face psychological interventions for cancer‐related distress.
What factors must be considered in ‘return to school’ following concussion and what strategies or accommodations should be followed? A systematic review
Authors: Laura K Purcell, Gavin A Davis, Gerard A Gioia
Journal: British Journal of Sports Medicine (2018)

Objective To evaluate the evidence regarding (1) factors affecting return to school (RTS) and (2) strategies/accommodations for RTS following a sport-related concussion (SRC) in children and adolescents. Design A systematic review of original studies specifically addressing RTS following concussion in the paediatric and sporting context. Data sources MEDLINE (Ovid), Embase (Ovid), PsycInfo (Ovid) electronic databases and the grey literature OpenGrey, ClinicalTrials.gov and Google Advanced. Eligibility criteria Studies were included if they were original research on RTS following SRC in children aged 5–18 years published in English between 1985 and 2017. Results A total of 180 articles were identified; 17 articles met inclusion criteria. Several factors should be considered for RTS after concussion, including: symptomatology; rest following injury; age/grade; and course load. On RTS after concussion, 17%–73% of students were provided academic accommodations or experienced difficulty with RTS. Students were more likely to obtain academic accommodations in schools with a concussion policy if they had a medical RTS letter and had regular medical follow-up after concussion. Conclusions Schools should have a concussion policy and offer individualised academic accommodations to students recovering from SRC on RTS; a medical letter should be provided to facilitate provision/receipt of academic accommodations; students should have early, regular medical follow-up following SRC to help with RTS and monitor recovery; students may require temporary absence from school after SRC; clinicians should assess risk factors/modifiers that may prolong recovery and require more intensive academic accommodations. PROSPERO registration number CRD42016039184 .
Surgeon Practice Patterns of Arthroscopic Partial Meniscectomy for Degenerative Disease in the United States
Authors: Philip F. Stahel, Peiqi Wang, Susan Hutfless, Eric McCarty, Philip S. Mehler, Greg Michael Osgood, Martin A. Makary
Journal: JAMA Surgery (2018)

Our previous study 2 using limited 5% Medicare data reported an 11.3% reintervention rate at 90 days and a 33% rate at 5 years.In a 5-year follow-up study of patients implanted with SNM for overactive bladder, Siegel et al 6 also reported only a 67% therapeutic success rate.We extend these results in, to our knowledge, the first large-scale, all-inclusive statewide study demonstrating high SNM device failure.We found that device malfunction was the second most common indication for early reinterventions and the predominant indication at 5 years.Moreover, our results demonstrate that even in the hands of high-volume surgeons, the invasive surgical reintervention rate remains very high.Limitations include generalizability to the entire US population, despite inclusion of all ages and data from all of New York, with its diverse population and practices.Use of billing codes may introduce some misclassification but is a valid method, particularly for reinterventions.Conclusions | Sacral neuromodulation is associated with a very high rate of failure, as measured by reinterventions, that occur at alarming rates within 5 years of placement.A device registry is urgently needed in this setting to advise stakeholders and assist future innovations.
Advanced age and prostate cancer specific mortality among geriatric patients with metastatic prostate cancer.
Authors: Grace L. Lu-Yao, William Kevin Kelly, Andrew E. Chapman
Journal: Journal of Clinical Oncology (2018)

319 Background: Data from clinical trials has shown that octogenarians are at increased risk for prostate cancer specific mortality (PCSM). Patients with significant comorbidities were excluded from the trials; consequently, the findings from clinical trials may not be applicable to the general population. Data on patients age 80+ with metastatic prostate cancer in the general population are limited. This population-based study assesses PCSM for metastatic prostate cancer patients diagnosed at age 70+. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, identified 418,982 patients diagnosed with prostate cancer at age 70+ between 01/01/2004-12/31/13, of which 12,749 had metastatic prostate cancer. The SEER database covers about 28% of the US population from all racial/ethnic groups. We used Cox proportional hazards (PH) model to calculate cause specific hazard ratio adjusted by age, race, marital status, urban-rural classification, income level, insurance type, primary cancer therapy, stage, and diagnosis period. Results: Of the 12,749 patients, 49.4% of the patients were in their 70's and 8.3% in their 90's+, with 79.1% of patients white and 57.1% married. About 17% of these patients received radiotherapy as their primary cancer treatment. The distribution of M1 subtype is: M1a (4.2%), M1b (68.5%), M1c (22.7%), M1 Not Otherwise Specified (or NOS,4.6%). The median survival for patients with M1 prostate cancer aged 70-79, 80-89 and 90+ were 25, 15, and 7 months, respectively. Compared to patients diagnosed in their 70's, there was 38% and 109% increase in PCSM among those diagnosed at ages 80-89 and 90+ respectively (Table). Conclusions: PCSM increases among geriatric patients with metastatic prostate cancer after accounting for potential confounding factors. Further investigation is needed to shed light on the underlying biological mechanisms. [Table: see text]