tbuckley/cabot-search huggingface dataset:
Doctors who was struck off for misconduct is restored to the register after changing his ways
Authors: Clare Dyer
Journal: BMJ (2020)

A doctor who was struck off the UK medical register in 2013 for misconduct has been allowed back on the register after a medical practitioners tribunal decided that he was now “a different person.”

Doctors who are struck off may apply after five years for restoration to the register, but few succeed. Of 13 who applied in 2019 only two were successful, and in 2018 only four of 14 applications were granted.

Babak Shokouhi, who qualified in Iran, was erased from the register in September 2013 after the second of two hearings by a medical practitioners tribunal.

At the first hearing, held in May of that year, the tribunal found that when …
Neutrophil-to-lymphocyte ratio as a predictor of oncologic outcomes in locally advanced non-metastatic clear cell renal carcinoma.
Authors: Gilberto Rodrigues, Pablo Sierra, Emanuel Albuquerque, Fabio Pescarmona Gallucci, Eder Nisi Ilario, Paulo Afonso de Carvalho, David Queiroz Borges Muniz, Alvaro Sarkis, Rafael Coelho, Mauricio Cordeiro, William Carlos Nahas
Journal: Journal of Clinical Oncology (2020)

661 Background: An elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with worse oncologic outcomes in several malignancies, its prognostic role in kidney cancer, specifically in the non metastatic setting is controversial. We aimed to evaluate if an elevated NLR in patients with locally advanced non metastatic clear cell renal cell carcinoma (CCRCC) is associated with a worse survival and/or a higher cancer recurrence rate. Methods: We retrospectively identified 880 nephrectomies performed between 01/2009 to 12/2016 in a single center, reviewed data from 478 consecutive radical nephrectomies (RN) for kidney tumors and identified 187 patients with locally advanced non-metastatic CCRCC patients (pT3-T4 N0M0). The cut-off point of NLR = 2.5 was obtained using the receiver operating curve analysis (ROC). NLR was obtained preoperatively and calculated by dividing absolute neutrophil count by absolute lymphocyte count. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method. Cox regression models were utilized to evaluate predictors of recurrence and survival. Results: Median follow up was 48.7 months. The 3 year OS was significantly lower for patients with NLR ≥ 2.5 than those with NLR &lt; 2.5 (70% vs 85%, p = 0.049). In patients with a Fuhrman nuclear grade of differentiation of 3-4, the median time to recurrence was significantly shorter for patients with NLR ≥ compared to those with NLR &lt; 4 (24 vs 55 months p 0.045). On multivariable analysis adjusted for NLR ≥ 2.5, microvascular invasion, sarcomatoid differentiation, tumor size and body mass index, only nuclear grade of differentiation was found to be an independent predictor for recurrence (hazard ratio= 2.18; 95% confidence interval [CI]: 1.07 – 4.92, p = 0.03). Conclusions: Patients with non-metastatic CCRCC with higher nuclear grade of differentiation and a high preoperative NLR have shorter RFS and worse OS compared to patients with lower NLR.
Fatal Case of Legionnaires’ Disease After Home Exposure to <i>Legionella pneumophila</i> Serogroup 3 — Wisconsin, 2018
Authors: Amy Schumacher, Anna Kocharian, Amanda Koch, John Marx
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

The case described in this report highlights the potential for people at risk for Legionnaires' disease to be exposed to Legionella through home water systems containing the bacteria and demonstrates the difficulty of removing the bacteria from residential settings.
Detection of Barrett’s oesophagus through exhaled breath using an electronic nose device
Authors: Yonne Peters, Ruud W M Schrauwen, Adriaan C Tan, Sanne K Bogers, Bart de Jong, Peter D Siersema
Journal: Gut (2020)

Timely detection of oesophageal adenocarcinoma (OAC) and even more so its precursor Barrett’s oesophagus (BO) could contribute to decrease OAC incidence and mortality. An accurate, minimally-invasive screening method for BO for widespread use is currently not available. In a proof-of-principle study in 402 patients, we developed and cross-validated a BO prediction model using volatile organic compounds (VOCs) analysis with an electronic nose device. This electronic nose was able to distinguish between patients with and without BO with good diagnostic accuracy (sensitivity 91% specificity 74%) and seemed to be independent of proton pump inhibitor use, the presence of hiatal hernia, and reflux. This technique may enable an efficient, well-tolerated, and sensitive and specific screening method to select high-risk individuals to undergo upper endoscopy.
Prevalence and clinical impact of <i>BRCA1/2</i> mutations in patients with <i>de novo</i> metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Nieves Martinez Chanza, Marie Tkint De Roodenbeke, Laurence Desmyter, Francoise Wilkin, Cindy Badoer, Isabelle Vandernoot, Guillaume Smits, Anna Ayako Accarain, Spyridon Sideris, Thierry Gil, Ahmad Awada, Thierry Andre Roumeguere, Anis Hamid
Journal: Journal of Clinical Oncology (2020)

44 Background: Somatic BRCA gene mutations ( sBRCAm) have been identified in a significant proportion of patients (pts) with castration resistant PC (CRPC), with mixed data regarding effect on CRPC therapies. However, the prevalence and clinical significance in mHSPC are not well characterized. Methods: Sequencing of primary tumor for sBRCA1/2 was performed in unselected pts with de novo mHSPC. We assessed the association of sBRCAm on time to CRPC (TTCRPC) and overall survival (OS) from diagnosis using Kaplan-Meier method, as well as PSA response (50% fall from baseline). Associations were evaluated using a Cox regression model with multivariable analyses adjusting for docetaxel use. Results: We identified 69 pts with de novo mHSPC, of whom 7 (10%) harbored a pathogenic sBRCA2m. Median age at diagnosis was 66 years. The majority were classified as high volume disease (n=54; 84%) with Gleason 9-10 grade (n=40; 61%). Therapies in the HSPC setting included ADT alone (n=29, 42%), ADT + Docetaxel (n=35, 51%), and ADT + Docetaxel + Abiraterone (n=5, 7%). Only 1 s BRCA2m case compared to 39 wild-type pts were treated with docetaxel. PSA response was achieved in 65 (96%) and PSA £ 0.2 ng/ml at 7 mos in 20 (31%) pts, without significant association with BRCA status ( p=0.13 and p=0.66, respectively). At a median FU of 29 mos, CRPC occurred in 44 (64%) pts with a median TTCRPC of 24 mos. TTCRP was numerically shorter for non-mutated pts compared to sBRCAm (22 vs. 40 mos, HR 0.5, p=0.23); there was no significant association with docetaxel use. In multivariate analyses, there was no significant association between sBRCAm and TTCRPC (HR 0.43, p=0.175). Median OS was 74 mos without any difference according to BRCA status ( p=0.30) nor docetaxel use ( p=0.14). Conclusions: In this real-world study of routine s BRCA1/2 assessment, we found a 10% prevalence in de novo mHSPC. Time to CRPC trended longer in the sBRCAm population despite less use of docetaxel, indicating that pts with sBRCAm appear to have at least similar outcomes with standard mHSPC therapies. Larger datasets correlating genomics with outcomes in this subset of pts are warranted.
Genotyping structural variants in pangenome graphs using the vg toolkit
Authors: Glenn Hickey, David Heller, Jean Monlong, Jonas A. Sibbesen, Jouni Sirén, Jordan Eizenga, Eric T. Dawson, Erik Garrison, Adam M. Novak, Benedict Paten
Journal: Genome biology (2020)

Structural variants (SVs) remain challenging to represent and study relative to point mutations despite their demonstrated importance. We show that variation graphs, as implemented in the vg toolkit, provide an effective means for leveraging SV catalogs for short-read SV genotyping experiments. We benchmark vg against state-of-the-art SV genotypers using three sequence-resolved SV catalogs generated by recent long-read sequencing studies. In addition, we use assemblies from 12 yeast strains to show that graphs constructed directly from aligned de novo assemblies improve genotyping compared to graphs built from intermediate SV catalogs in the VCF format.
Faeces and vaccines could be the key to tackling antimicrobial resistance
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Relying on the discovery of new antibiotics as the main solution to antimicrobial resistance (AMR) is not realistic and scientists should instead be looking to alternatives such as vaccines and faecal transplantations, according to a researcher from the National Institute for Biological Standards and Control.

Gregory Amos, who heads up the microbiome section of the standards body—part of the Medicines and Healthcare Products Regulatory Agency—said that multiple strategies are needed to overcome AMR and, while “new antibiotics would be nice, what we really need to do is reduce our dependency and usage of antibiotics.”

He suggested this could be …
Erratum: Corrigendum: Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer
Authors: Yufei Wang, James D McKay, Thorunn Rafnar, Zhaoming Wang, Maria N Timofeeva, Peter Broderick, Xuchen Zong, Marina Laplana, Yongyue Wei, Younghun Han, Amy Lloyd, Manon Delahaye-Sourdeix, Daniel Chubb, Valerie Gaborieau, William Wheeler, Nilanjan Chatterjee, Gudmar Thorleifsson, Patrick Sulem, Geoffrey Liu, Rudolf Kaaks, Marc Henrion, Ben Kinnersley, Maxime Vallée, Florence Le Calvez-Kelm, Victoria L Stevens, Susan M Gapstur, Wei V Chen, David Zaridze, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Hans E Krokan, Maiken Elvestad Gabrielsen, Frank Skorpen, Lars Vatten, Inger Njølstad, Chu Chen, Gary Goodman, Simone Benhamou, Tonu Vooder, Kristjan Välk, Mari Nelis, Andres Metspalu, Marcin Lener, Jan Lubiński, Mattias Johansson, Paolo Vineis, Antonio Agudo, Francoise Clavel-Chapelon, H Bas Bueno-de-Mesquita, Dimitrios Trichopoulos, Kay-Tee Khaw, Mikael Johansson, Elisabete Weiderpass, Anne Tjønneland, Elio Riboli, Mark Lathrop, Ghislaine Scelo, Demetrius Albanes, Neil E Caporaso, Yuanqing Ye, Jian Gu, Xifeng Wu, Margaret R Spitz, Hendrik Dienemann, Albert Rosenberger, Li Su, Athena Matakidou, Timothy Eisen, Kari Stefansson, Angela Risch, Stephen J Chanock, David C Christiani, Rayjean J Hung, Paul Brennan, Maria Teresa Landi, Richard S Houlston, Christopher I Amos
Journal: Nature Genetics (2017)
Variance in symptom assessment between patient and caregiver: A prospective study of patients staged as metastatic prostate cancer—An interim analysis.
Authors: Sadie Swift, Jane Vitin, Hillary Prime, Robert Topp, Paul Dato, Edward Cohen, Franklin Gaylis
Journal: Journal of Clinical Oncology (2020)

56 Background: Closely monitored and managed patient reported outcomes (PROs) can impact survival of cancer patients. However, the reliability and validity of patients’ self-reported symptoms are somewhat open to question, as past studies have shown that patients may underreport health information to their physicians. Identifying where the discrepancy between PROs and actual symptomology lies may be important in improving providers’ grasp of a patients’ disease state. The purpose of this study is to compare prostate cancer patients’ reports of their symptoms and functioning with the patients’ caregivers’ perception of the same factors. Methods: 50 patients with metastatic prostate cancer on Androgen Deprivation Therapy (ADT) and their caregivers were asked to independently complete the Functional Assessment of Cancer Therapy- Prostate (FACT-P), Brief Pain Inventory- Short Form (BPI-SF), and EQ-5D-3L questionnaires in relation to the patient’s condition. Patient and caregiver dyad responses to these instruments were then compared by t-tests for continuous measures and Chi-Square for discrete measures. Results: Not all patient and caregiver dyads completed all of the data collection instruments. Patients are more likely than caregivers to rate themselves as having fewer limitations on mobility (n=47, p≤0.001), less pain and/or discomfort (n=46, p≤0.001), and less limitations with self-care (n=46, p≤0.001). Furthermore, caregivers were more likely to rate patients as having more anxiety (n=47, p≤0.001), more severe pain (n=20, p&lt;0.05), and lower overall physical wellbeing scores (n=40, p&lt;0.005). Ratings for emotional and social functioning were not significantly different between the patient and their caregiver. Conclusions: Overall a high degree of agreement was reported between patient and caregiver ratings of the patient’s symptoms and functioning; however, when differences were present the caregivers consistently rated the patients’ conditions as more severe, particularly in relation to physical symptoms. This may indicate that patients are minimizing their symptoms when reporting to their physicians.
Negative pressure wound therapy versus standard treatment in patients with acute conflict-related extremity wounds: a pragmatic, multisite, randomised controlled trial
Authors: Andreas Älgå, Rawand Haweizy, Khaldoon Bashaireh, Sidney Wong, Kalle Conneryd Lundgren, Johan von Schreeb, Jonas Malmstedt
Journal: The Lancet Global Health (2020)

In armed conflict, injuries among civilians are usually complex and commonly affect the extremities. Negative pressure wound therapy (NPWT) is an alternative to standard treatment of acute conflict-related extremity wounds. We aimed to compare the safety and effectiveness of NPWT with that of standard treatment.In this pragmatic, randomised, controlled superiority trial done at two civilian hospitals in Jordan and Iraq, we recruited patients aged 18 years or older, presenting with a conflict-related extremity wound within 72 h after injury. Participants were assigned (1:1) to receive either NPWT or standard treatment. We used a predefined, computer-generated randomisation list with three block sizes. Participants and their treating physicians were not masked to treatment allocation. The primary endpoint was wound closure by day 5. The coprimary endpoint was net clinical benefit, defined as a composite of wound closure by day 5 and freedom from any bleeding, wound infection, sepsis, or amputation of the index limb. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02444598, and is closed to accrual.Between June 9, 2015, and Oct 24, 2018, 174 patients were randomly assigned to either the NPWT group (n=88) or the standard treatment group (n=86). Five patients in the NPWT group and four in the standard treatment group were excluded from the intention-to-treat analysis. By day 5, 41 (49%) of 83 participants in the NPWT group and 49 (60%) of 82 participants in the standard treatment group had closed wounds, with an absolute difference of 10 percentage points (95% CI -5 to 25, p=0·212; risk ratio [RR] 0·83, 95% CI 0·62 to 1·09). Net clinical benefit was seen in 33 (41%) of 81 participants in the NPWT group and 34 (44%) of 78 participants in the standard treatment group, with an absolute difference of 3 percentage points (95% CI -12 to 18, p=0·750; RR 0·93, 95% CI 0·65 to 1·35). There was one in-hospital death in the standard treatment group and none in the NPWT group. The proportion of participants with sepsis, bleeding leading to blood transfusion, and limb amputation did not differ between groups.NPWT did not yield superior clinical outcomes compared with standard treatment for acute conflict-related extremity wounds. The results of this study not only question the use of NPWT, but also question the tendency for new and costly treatments to be introduced into resource-limited conflict settings without supporting evidence for their effectiveness. This study shows that high-quality, randomised trials in challenging settings are possible, and our findings support the call for further research that will generate context-specific evidence.The Stockholm County Council, the Swedish National Board of Health and Welfare, and Médecins Sans Frontières.
Evolving role of biomaterials in diagnostic and therapeutic radiation oncology
Authors: Siyu Shi, Ravi Vissapragada, Joseph Abi Jaoude, Caroline Huang, Anmol Mittal, Elisa Liu, Jim Zhong, Vivek Kumar
Journal: Bioactive Materials (2020)

Radiation therapy to treat cancer has evolved significantly since the discovery of x-rays. Yet, radiation therapy still has room for improvement in reducing side effects and improving control of cancer. Safer and more effective delivery of radiation has led us to novel techniques and use of biomaterials. Biomaterials in combination with radiation and chemotherapy have started to appear in pre-clinical explorations and clinical applications, with many more on the horizon. Biomaterials have revolutionized the field of diagnostic imaging, and now are being cultivated into the field of theranostics, combination therapy, and tissue protection. This review summarizes recent development of biomaterials in radiation therapy in several application areas.
Systematic Dementia Screening by Multidisciplinary Team Meetings in Nursing Homes for Reducing Emergency Department Transfers
Authors: Yves Rolland, Neda Tavassoli, Philipe de Souto Barreto, Amélie Perrin, Clarisse Laffon de Mazières, Thomas Rapp, Sophie Hermabessière, Elodie Tournay, Bruno Vellas, Sandrine Andrieu
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Dementia is often underdiagnosed in nursing homes (NHs). This potentially results in inappropriate care, and high rates of emergency department (ED) transfers in particular. <h3>Objective</h3> To assess whether systematic dementia screening of NH residents combined with multidisciplinary team meetings resulted in a lower rate of ED transfer at 12 months compared with usual care. <h3>Design, Setting, and Participants</h3> Multicenter, cluster randomized trial with NHs as the unit of randomization. The IDEM (Impact of Systematic Tracking of Dementia Cases on the Rate of Hospitalization in Emergency Care Units) trial took place at 64 public and private NHs in France. Recruitment started on May 1, 2010, and was completed on March 31, 2012. Residents who were aged 60 years or older, had no diagnosed or documented dementia, were not bedridden, had lived in the NH for at least 1 month at inclusion, and had a life expectancy greater than 12 months were included. The residents were followed up for 18 months. The main study analyses were completed on October 14, 2016. <h3>Intervention</h3> Two parallel groups were compared: an intervention group consisting of NHs that set up 2 multidisciplinary team meetings to identify residents with dementia and to discuss an appropriate care plan, and a control group consisting of NHs that continued their usual practice. During the inclusion period of 23 months, all residents of participating NHs who met eligibility criteria were included in the study. <h3>Main Outcomes and Measures</h3> The primary end point (ED transfer) was analyzed at 12 months, but the residents included were followed up for 18 months. <h3>Results</h3> A total of 64 NHs participated in the study and enrolled 1428 residents (mean [SD] age, 84.7 [8.1] years; 1019 [71.3%] female): 599 in the intervention group (32 NHs) and 829 in the control group (32 NHs). The final study visit was completed by 1042 residents (73.0%). The main reason for early discontinuation was death (318 residents [22.7%]). The intervention did not reduce the risk of ED transfers during the 12-month follow-up: the proportion of residents transferred at least once to an ED during the 12-month follow-up was 16.2% in the intervention group vs 12.8% in the control group (odds ratio, 1.32; 95% CI, 0.83-2.09;<i>P</i> = .24). <h3>Conclusions and Relevance</h3> This study failed to demonstrate that systematic screening for dementia in NHs resulted in fewer ED transfers. The findings do not support implementation of multidisciplinary team meetings for systematic dementia screening of all NH residents, beyond the national recommendations for dementia diagnosis, to reduce ED transfers. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01569997
Promising new broad spectrum antibiotic compound identified by algorithm
Authors: Elisabeth Mahase
Journal: BMJ (2020)

A new broad spectrum antibiotic compound, which appears to be effective against dozens of bacterial strains and has a different chemical structure to existing antibiotics, has been identified by researchers at MIT.

The team used a machine learning algorithm to assess thousands of compounds and identify potential antibiotic candidates. It selected a molecule which was previously investigated as a potential diabetes drug and has now been named halicin after the fictional artificial intelligence system …
A Phase 1, Five-Period, Five-Treatment, Randomized Crossover Study of the Pharmacokinetics (PK) and Pharmacodynamics (PD) of Epinephrine After Administration of Intranasal (IN) ARS-1 and Intramuscular (IM) Epinephrine to Healthy Volunteers
Authors: Sarina Tanimoto, F. Estelle Simons, Richard Lockey, Phillip Lieberman, Michael Kaliner, Richard Lowenthal
Journal: Journal of Allergy and Clinical Immunology (2020)
Coronaviruses in animals and humans
Authors: Lisa F P Ng, Julian A Hiscox
Journal: BMJ (2020)

Controlling outbreaks will require detailed knowledge of their biology and behaviour Coronaviruses have been around for many years and were first discovered in the 1960s. They include viruses contributing to the common cold (HCoV-229E) and a variety of animal and avian coronaviruses, such as
Outcomes of acute myeloid leukemia with myelodysplasia related changes depend on diagnostic criteria and therapy
Authors: Guillermo Montalban‐Bravo, Rashmi Kanagal‐Shamanna, Caleb A. Class, Koji Sasaki, Farhad Ravandi, Jorge E. Cortes, Naval Daver, Koichi Takahashi, Nicholas J. Short, Courtney D. DiNardo, Elias Jabbour, Gautam Borthakur, Kiran Naqvi, Ghayas C. Issa, Marina Konopleva, Joseph D. Khoury, Mark Routbort, Sherry Pierce, Kim‐Anh Do, Carlos Bueso‐Ramos, Keyur Patel, Hagop Kantarjian, Guillermo Garcia‐Manero, Tapan M. Kadia
Journal: American Journal of Hematology (2020)

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a heterogeneous disorder defined by multilineage dysplasia, myelodysplastic syndrome (MDS)-related karyotype, or history of prior MDS. We evaluated 415 patients with AML-MRC treated from 2013 to 2018 and analyzed their clinical outcomes based on the diagnostic criteria of AML-MRC, therapy type and mutation profile. Criteria for AML-MRC included: cytogenetic abnormalities (AML-MRC-C) in 243 (59%), prior history of MDS in 75 (18%) including 47 (11%) with previously untreated MDS (AML-MRC-H) and 28 (7%) with previously treated MDS (AML-MRC-TS), and 97 (23%) with multilineage dysplasia (AML-MRC-M). Median age was 70 years (range 18-94). Among 95 evaluable patients, a total of 37 (39%) had secondary-type (ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2) mutations. Mutations in ASXL1, BCOR, SF3B1, SRSF2, and U2AF1 tended to appear in dominant clones. By multivariate analysis, AML-MRC subtype, age and serum LDH levels were independent predictors of outcome, with patients with AML-MRC-M (HR 0.56, CI 0.38-0.84, P = .004) and AML-MRC-H having better OS. Compared to a cohort of 468 patients with AML without MRC, patients with AML-MRC-M/AML-MRC-H had similar outcomes to those with intermediate risk AML by European LeukemiaNet criteria. Intensive therapy was associated with improved OS in patients with AML-MRC-M (HR 0.42, CI 0.19-0.94, P = .036) and with improved EFS in AML-MRC-M and AML-MRC-H (HR 0.26, CI 0.10-0.63, P = .003). This data suggests that not all diagnostic criteria for AML-MRC define high-risk patients and that specific subgroups may benefit from different therapeutic interventions.