tbuckley/cabot-search huggingface dataset:
Abstract P5-14-14: A validated clinical risk prediction model for cardiac toxicity in patients treated with antiHER2 agents
Authors: Pooja P Advani, Lauren Cornell, Zhuo Li, Jordan Ray, Catalina Sanchez, Armando Villanueva, Taryn Smith, Alvaro Moreno-Aspitia
Journal: Cancer Research (2020)

Abstract Background: Cardiac toxicity (CT) in the form of left ventricular systolic dysfunction is a well-known complication of anti-HER2 therapy. Prior clinical trial data has suggested potential factors associated with increased risk for CT. We sought to develop a clinical risk prediction model from real world patients to better identify patients who may be at higher risk for CT. Methods: Patients treated with anti-HER2 agents at all Mayo Clinic sites from Jan 2008 to July 2015 were reviewed. Patient data including age, race, body mass index, comorbidities, smoking history, baseline ejection fraction (EF), presence of left ventricular hypertrophy (LVH), prior cancer treatments, number of anti-HER2 agents used, and cardiac medication use were recorded. Factors were compared in patients with and without development of CT. Cox regression models were used to identify univariate and multivariate predictors of CT. A risk score was then assigned based on the final multivariable model. Results: 604 patients were included in final analysis. Median follow-up 2.9 yrs; median age: 57 yr; baseline EF: 64%. One yr CT rate was 7%. Independent predictors of CT were age, baseline EF, LVH, and anthracycline use (C index=0.74). Based on model coefficient, scores of 1, 1, 2 and 3 were assigned to age&amp;gt;55, EF &amp;lt;60%, anthracycline exposure and LVH, respectively. Two random samples of 300 patients were created out of the original cohort for internal validation of the risk score model. In each, the risk score was found to be a highly significant predictor for CT with C index of 0.72 {HR 2.13 (95% CI 1.57-2.90), p &amp;lt;0.001} and 0.77 {HR 2.45 (95% CI 1.74-3.44), p &amp;lt;0.001}. Conclusions: Patients with risk factors of older age, lower baseline EF, anthracycline use and LVH are at increased risk for CT when treated with anti-HER2 agents. Using a risk prediction model at therapy initiation may enhance identification of patients who benefit from cardiology referral, closer cardiac monitoring, and/or prophylactic treatment while on anti-HER2 targeted therapy. Table 1. Multivariable Cox regression model predicting cardiac dysfunctionParameterParameter EstimateHR (95%CI)p valueScoreAge &amp;gt;550.909552.48(1.27, 4.84)0.00751EF&amp;lt;600.634361.89(1.01, 3.53)0.04751Anthracycline Exposure1.046132.85(1.48, 5.46)0.00162Baseline LVH1.633565.12(2.04,12.85)&amp;lt;0.0013 Citation Format: Pooja P Advani, Lauren Cornell, Zhuo Li, Jordan Ray, Catalina Sanchez, Armando Villanueva, Taryn Smith, Alvaro Moreno-Aspitia. A validated clinical risk prediction model for cardiac toxicity in patients treated with antiHER2 agents [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-14.
David Oliver: Racism in medicine—what ethnic minority doctors told me on Twitter
Authors: David Oliver
Journal: BMJ (2020)

When my editor asked me to write a column for this issue, I was hesitant. As a white, male, middle class British doctor, what could I possibly say that was useful?

I could emphasise that I work alongside doctors, nurses, and allied professionals from ethnic minority backgrounds and that, without their commitment, our health and care services would collapse.

I could write about the data. For instance, 13.1% of the NHS workforce have non-British nationality,1 and 20.7% of NHS doctors are from ethnic minority backgrounds23—higher in general practice. Lower paid occupations such as social care rely even more on overseas and ethnic minority recruits.

I could describe the mismatch between their numbers in the rank and file and the number of doctors in high profile leadership positions. They don’t reflect the balance of the workforce in terms of gender or ethnicity. Speaker and panel line-ups at medical conferences, and expert media talking heads on …
Laboratory readiness and response for novel coronavirus (2019-nCoV) in expert laboratories in 30 EU/EEA countries, January 2020
Authors: Chantal B.E.M. Reusken, Eeva K. Broberg, Bart Haagmans, Adam Meijer, Victor M. Corman, Anna Papa, Remi Charrel, Christian Drosten, Marion Koopmans, Katrin Leitmeyer
Journal: Eurosurveillance (2020)

Timely detection of novel coronavirus (2019-nCoV) infection cases is crucial to interrupt the spread of this virus. We assessed the required expertise and capacity for molecular detection of 2019-nCoV in specialised laboratories in 30 European Union/European Economic Area (EU/EEA) countries. Thirty-eight laboratories in 24 EU/EEA countries had diagnostic tests available by 29 January 2020. A coverage of all EU/EEA countries was expected by mid-February. Availability of primers/probes, positive controls and personnel were main implementation barriers.
Abstract P5-08-24: Impaired glucose tolerance decreases mammographic breast density in Japanese women
Authors: Ken Uchida, Naruki Kitano, Daisuke Yamaguchi, Hiroko Nogi, Makiko Kamio, Hiroshi Takeyama
Journal: Cancer Research (2020)

Abstract Background; Many studies have demonstrated an association between diabetes and breast cancer risk. Purpose; We examined whether fasting glucose and hemoglobin A1c (HbA1c) are associated with mammographic breast density in Japanese women. Methods; Study consisted of 6,203 women who attend breast cancer screening with the medical health check-up (2014-2019). We used mammographic breast density assessed at the first breast screening. Fasting serum glucose and HbA1c were examined at the same day on the breast cancer screening. The association between breast density and fasting serum glucose and HbA1c were analyzed by logistic regression adjusted for potential confounding factors. Serum glucose and HbA1c levels were calculated with continuous variables. BI-RADS c and d were defined as dense breast tissue. Results; Of 6,203 women with mean age of 51 years, dense breast tissue was present in 60.0 % of participants. 960 (15.1%) had hyper-glycemia (≥100) and 2,830 (45.62%) had hyper-HbA1c (&amp;gt;5.5%). As table 1 illustrates, hyper-glycemia and hyper-HbA1c were significantly inversely associated with dense breast tissue, (serum glucose: odds ratio; 0.987 confidence interval: 0.982-0.992, p&amp;lt;0.01, HbA1c: odds ratio; 0.699, confidence interval:0.614-0.796, p&amp;lt;0.01). There was no effect modification of these associations by menopausal status, body mass index (BMI) and other confounding factors. Conclusions; Hyper-glycemia and hyper-HbA1c are associated with a decrease in mammographic breast density in Japanese women. Table 1 The relations of glucose intolerance and mammographic breast density.odds ratioconfidence intervalp valueFasting serum glucose0.9870.982-0.992&amp;lt;0.01HbA1c0.6990.614-0.796&amp;lt;0.01 Citation Format: Ken Uchida, Naruki Kitano, Daisuke Yamaguchi, Hiroko Nogi, Makiko Kamio, Hiroshi Takeyama. Impaired glucose tolerance decreases mammographic breast density in Japanese women [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-24.
Abstract 239: 911 Caller Description of Seizure-Like Symptoms and Delays to Starting Telecommunicator CPR
Authors: Kara Kronemeyer, Kameron Shee, Vatsal Chikani, Normandy Villa, Lesley Osborn, Micah Panczyk, Bentley Bobrow
Journal: Circulation (2019)

Background: Bystander cardiopulmonary resuscitation (BCPR) improves survival after out-of-hospital cardiac arrest (OHCA). Identifying delays to starting Telecommunicator CPR (TCPR) may improve outcomes. Identifying terms callers use to describe seizure-like symptoms may improve accuracy and expedite TCPR. Methods: A total of 586 confirmed OHCA calls from 3 regional 911 centers in Arizona were reviewed between 2013 to 2016. Frequency of terms callers use to describe seizure-like symptoms were assessed. Demographics and TCPR process measures were compared between the seizure and non-seizure cohorts using Chi-square analysis for categorical variables and Kruskal-Wallis test for continuous variables. Other data points were time to start of seizure description, time to end of description, and time to start of seizure intervention. Results: There were 545 calls after exclusions. Twenty-six (.05%) had seizure-like symptoms described. Of these, “seizure” or “seizing” were used in 22 (84.6%) calls, “shaking” in 6 (23.1%), “cramping up” in 2 (7.7%) and convulsing in 2 (7.7%). Descriptions were more common in witnessed arrests [65.4% (17/26) vs. 34.6% (9/26); p=0.045] and in younger patients [median age=57 (QI=45, Q3=68) vs. 66 (Q1=51, Q3=77); p=0.036.] In calls with descriptions, telecommunicators were less likely to recognize OHCA [56.0% (14/25) vs. 74.5% (382/513), .031% (17/545) missing; (p=0.041] but bystanders were not less likely to start compressions [42.3% (11/26) vs. 57.6% (289/501), .033% (18/545) missing; p=0.122]. Median time to recognition in calls with descriptions was delayed vs. calls without descriptions [142 s (Q1=74 s, Q3=194 s), n=13, vs. 63 s (Q1=40 s, Q3=112 s), n=336; p=0.005], as was time to first chest compression [262 s (Q1=182 s, Q3=291 s), n=6 vs. 154 s (Q1=110 s, Q3=206 s), n=155; p=0.011]. Median times to start of description, end of description, and start of intervention were respectively: 33 s (Q1=20 s, Q3=40 s; 54 s (Q1=37 s, Q3=138 s; and 50 s (Q1=38 s, Q3=162 s). Conclusion: Description of seizure-like symptoms were uncommon and were associated with reduced and delayed OHCA recognition and delayed start of compressions.
Medicinal chemistry strategies toward host targeting antiviral agents
Authors: Xingyue Ji, Zhuorong Li
Journal: Medicinal Research Reviews (2020)

Abstract Direct‐acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow‐spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad‐spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed.
Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice
Authors: Collin Challis, Acacia Hori, Timothy R. Sampson, Bryan B. Yoo, Rosemary C. Challis, Adam M. Hamilton, Sarkis K. Mazmanian, Laura A. Volpicelli-Daley, Viviana Gradinaru
Journal: Nature Neuroscience (2020)
Abstract 17807: Cyclophilin D Deficiency Attenuates Ca2+ Waves During Mitochondrial Depolarization in Mouse Cardiomyocytes
Authors: Richard Gordan, Nadezhda Fefelova, Lai-Hua Xie
Journal: Circulation (2013)

Recent studies have indicated that mitochondrial Ca flux plays a significant role in modulating micro-domain Ca2+ levels, near the ryanodine receptors, and spontaneous Ca wave (CaW) behaviors in is...
Abstract P4-02-19: First reported use of the Faxitron LOCalizer™ Radiofrequency Identification (RFID) system in the axilla- A pilot trial in targeted axillary dissection (TAD)
Authors: Wolfram Malter, Christian Eichler, Julian Puppe, Fabishy Thangarajah, Peter Mallmann, Barbara Krug, Mathias Warm, Johannes Holtschmidt
Journal: Cancer Research (2020)

Abstract Introduction: Adequately marking suspicious lymph nodes before neoadjuvant chemotherapy in breast cancer patients is commonly done by introducing a titanium clip followed by stereotactic hook wire location. However, clip dislocation and/or wire dislocation are common problems. Furthermore, locating a clip within the axilla is problematic since stereotactic location may be anatomically challenging. An ideal solution would be a clip which can be easily found without the use of a stereotactic intervention. This pilot trial proves the concept of using radiofrequency identification devices (RFID) in targeted axillary dissection (TAD).Methods: This pilot trial represents a single center, consecutively recruited, evaluation (n=10) for targeted axillary dissection using the Faxitron LOCalizer™ radiofrequency identification chip system. Patients were given the choice between wire guided TAD vs. LOCalizer™ TAD. Primary endpoints were: percentage of successful location /failure to locate. Secondary endpoints were major and minor complication rates as well as surgeon evaluated outcome.Results: Primary endpoints showed a 100% location rate of the suspicious lymph nodes at a 0% major complication (revision surgery) rate. Additional guided wire marking was not necessary for lymph node location. Surgeons evaluated the new system as being safe to use and only slightly more difficult to place than a standard clip or a wire system.Conclusion: This pilot trial proved the concept of TAD via a RFID system. When using this system, preoperative stereotactic lymph node marking is no longer required, thus patients may be spared additional x-ray exposure. Using the LOCalizer™ system should therefore be considered for any TAD. Citation Format: Wolfram Malter, Christian Eichler, Julian Puppe, Fabishy Thangarajah, Peter Mallmann, Barbara Krug, Mathias Warm, Johannes Holtschmidt. First reported use of the Faxitron LOCalizer™ Radiofrequency Identification (RFID) system in the axilla- A pilot trial in targeted axillary dissection (TAD) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-19.
Defining “stable chronic hypercapnia” in patients with COPD: the physiological perspective
Authors: Caroline Hedsund, Torgny Rostrup Wilcke, Ronan M.G. Berg
Journal: European Respiratory Journal (2020)

We read with interest the “European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD” [1]. In recent years, several studies have attempted to improve outcomes by using home non-invasive ventilation in patients with end-stage COPD who suffer from chronic hypercapnic respiratory failure (CHRF). As noted in the guidelines, the definition of “stable chronic hypercapnia” following an acute exacerbation has historically been ambiguous, which has probably contributed to the inconsistent findings across clinical trials of home non-invasive ventilation [2]. A time period of 2–4 weeks is required before a state of “stable chronic hypercapnia” is likely to be present following an acute COPD exacerbation <http://bit.ly/2D4lOok>
Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota
Authors: Hiroko Nagao-Kitamoto, Jhansi L. Leslie, Sho Kitamoto, Chunsheng Jin, Kristina A. Thomsson, Merritt G. Gillilland, Peter Kuffa, Yoshiyuki Goto, Robert R. Jenq, Chiharu Ishii, Akiyoshi Hirayama, Anna M. Seekatz, Eric C. Martens, Kathryn A. Eaton, John Y. Kao, Shinji Fukuda, Peter D. R. Higgins, Niclas G. Karlsson, Vincent B. Young, Nobuhiko Kamada
Journal: Nature Medicine (2020)
Comparison of risk factor associations in UK Biobank against representative, general population based studies with conventional response rates: prospective cohort study and individual participant meta-analysis
Authors: G David Batty, Catharine R Gale, Mika Kivimäki, Ian J Deary, Steven Bell
Journal: BMJ (2020)

Abstract Objective To compare established associations between risk factors and mortality in UK Biobank, a study with an exceptionally low rate of response to its baseline survey, against those from representative studies that have conventional response rates. Design Prospective cohort study alongside individual participant meta-analysis of other cohort studies. Setting United Kingdom. Participants Analytical sample of 499 701 people (response rate 5.5%) in analyses in UK Biobank; pooled data from the Health Surveys for England (HSE) and the Scottish Health Surveys (SHS), including 18 studies and 89 895 people (mean response rate 68%). Both study populations were linked to the same nationwide mortality registries, and the baseline age range was aligned at 40-69 years. Main outcome measure Death from cardiovascular disease, selected malignancies, and suicide. To quantify the difference between hazard ratios in the two studies, a ratio of the hazard ratios was used with HSE-SHS as the referent. Results Risk factor levels and mortality rates were typically more favourable in UK Biobank participants relative to the HSE-SHS consortium. For the associations between risk factors and mortality endpoints, however, close agreement was seen between studies. Based on 14 288 deaths during an average of 7.0 years of follow-up in UK Biobank and 7861 deaths over 10 years of mortality surveillance in HSE-SHS, for cardiovascular disease mortality, for instance, the age and sex adjusted hazard ratio for ever having smoked cigarettes (versus never) was 2.04 (95% confidence interval 1.87 to 2.24) in UK Biobank and 1.99 (1.78 to 2.23) in HSE-SHS, yielding a ratio of hazard ratios close to unity (1.02, 0.88 to 1.19). The overall pattern of agreement between studies was essentially unchanged when results were compared separately by sex and when baseline years and censoring dates were aligned. Conclusion Despite a very low response rate, risk factor associations in the UK Biobank seem to be generalisable.
Radiologist who claimed to be GP to write road injury reports is struck off
Authors: Clare Dyer
Journal: BMJ (2020)

A former consultant radiologist who described himself as a GP when writing a medicolegal report on a road traffic injury has been struck off the UK medical register for persistent dishonesty.

David Foster also claimed to be a GP in a curriculum vitae sent to an agency that assigns doctors to prepare reports on people who have been injured in road traffic crashes.

Foster, who qualified in 1972 and practised for years as a radiologist in Wales, did not attend his hearing. He had applied for voluntary erasure, but the …
Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity
Authors: Maria Raffaella Barbaro, Cesare Cremon, Antonio Maria Morselli-Labate, Antonio Di Sabatino, Paolo Giuffrida, Gino Roberto Corazza, Michele Di Stefano, Giacomo Caio, Giovanni Latella, Carolina Ciacci, Daniele Fuschi, Marianna Mastroroberto, Lara Bellacosa, Vincenzo Stanghellini, Umberto Volta, Giovanni Barbara
Journal: Gut (2020)

Non-coeliac gluten sensitivity (NCGS) is characterised by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing foods, in the absence of coeliac disease (CD) and wheat allergy. No biomarkers are available to diagnose NCGS and the gold standard double-blind placebo-controlled gluten challenge is clinically impractical. The aim of our work was to investigate the role of serum zonulin as a diagnostic biomarker of NCGS and to develop a diagnostic algorithm.In a multicentre study, we enrolled 86 patients with either self-reported or double-blind confirmed NCGS, 59 patients with diarrhoea-predominant IBS (IBS-D), 15 patients with CD and 25 asymptomatic controls (AC). Zonulin serum levels were assessed and the associated diagnostic power calculated. Clinical and symptomatic data were recorded. The effect of diet on zonulin levels was evaluated in a subgroup of patients with NCGS.Compared with ACs, the NCGS, irrespective of modality of diagnosis, and patients with CD had significantly increased levels of zonulin, as did both NCGS and patients with CD compared with participants with IBS-D. Self-reported NCGS showed increased zonulin levels compared with double-blind confirmed and not-confirmed NCGS. Six-month wheat avoidance significantly reduced zonulin levels only in HLA-DQ2/8-positive participants with NCGS. The diagnostic accuracy of zonulin levels in distinguishing NCGS from IBS-D was 81%. After exclusion of CD, a diagnostic algorithm combining zonulin levels, symptoms and gender improved the accuracy to 89%.Zonulin can be considered a diagnostic biomarker in NCGS and combined with demographic and clinical data differentiates NCGS from IBS-D with high accuracy. Wheat withdrawal was associated with a reduction in zonulin levels only in NCGS carrying HLA genotype.
Pemetrexed-carboplatin adjuvant chemotherapy with or without gefitinib in resected stage IIIA-N2 non-small cell lung cancer harbouring EGFR mutations: A randomized phase II study.
Authors: Si-Yu Wang, Wei Ou, Ning Li, Haibo Sun, Liang Zhang, Qin Fang
Journal: Journal of Clinical Oncology (2013)

7519 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations. The BR.19 trial exploring the role of adjuvant gefitinib in resected early stage NSCLC (stage IB 49%, II 38%, III 13%) did not show significant progression-free survival (PFS) or overall survival (OS) improvement in all patients. The efficacy of gefitinib following adjuvant chemotherapy in patients with EGFR mutation is unknown. Methods: In this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations (either the exon 19 deletion or L858R point mutation) were randomly assigned to receive pemetrexed (500mg/m 2 ) and carboplatin (AUC=5), administered every 21 days for 4 cycles, followed with (n=30) or without (n=30) gefitinib (250mg per day) for 6 months. The primary end point was PFS. The second end point was OS. Results: From August 2008 toSeptember 2011, 60 patients (35 males and 25 females) were included in our center. Of the 60 patients (56 adenocarcinomas, 2 squamous cell carcinomas, 2 adenosquamous carcinomas), 20 patients (33.3%) had exon 19 deletion mutation, 40 (66.7%) patients had exon 21 L858R point mutation. The most common adverse event was rash (43.3%, 13 of 30) in the pemetrexed and carboplatin (PC)-gefitinib group and the addition of gefitinib to chemotherapy was well tolerated. The PFS was significantly longer among those who received PC-gefitinib than among those who received PC alone (median,39.8 months vs 27.0 months; hazard ratio [HR],0.369; 95% confidence interval [CI], 0.161-0.847; P=0.014). There was no significant difference in OS between the two group(median,41.6 months vs 32.6 months,P=0.066). The rates of 2-year PFS and OS were 78.9% and 92.4% in PC-gefitinib group, and 54.2% and 77.4% in PC alone group, respectively. Conclusions: The addition of gefitinib to pemetrexed and carboplatin adjuvant therapy showed significant improvement in PFS for patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations.
Mast cell activation test using patient‐derived mast cells exhibits distinct combinatorial phenotypic profiles among allergic patients
Authors: Issan Yee San Tam, Hang Yung Alaster Lau, See‐Ying Tam, Tak Hong Lee
Journal: Allergy (2020)

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