tbuckley/cabot-search huggingface dataset:
Human factors in risk management masterclass
Authors: Niroshan Sivathasan, Mark-Alexander Sujan
Journal: BMJ (2010)

“Medical staff reported that error is important but difficult to discuss and not handled well in their hospital,” states the BMJ .1 Though not an obvious association, patient safety and safety in the airline industry have numerous parallels. Crew resource management (CRM) from the airline industry has been adapted to team resource management (TRM) for other industries, most notably health care. Terema is a key provider of “ te am re source ma nagement” skills to the NHS, using analogies and lessons from the aviation industry. After numerous enthusiastic recommendations from colleagues, we attended this evidence based masterclass in March 2010.

This course provides an introduction to human factors and their impact on patient safety, and is suitable for raising awareness among all those involved in health care, but especially doctors and nurses. Almost three quarters of errors in aviation have a human cause, but nobody knows what the proportion is in health care. To encourage good practice from the outset, certain hospitals, such as University College Hospital London, send …
Adjuvant Treatment for <i>POLE</i> Proofreading Domain–Mutant Cancers: Sensitivity to Radiotherapy, Chemotherapy, and Nucleoside Analogues
Authors: Inge C. Van Gool, Emily Rayner, Elisabeth M. Osse, Remi A. Nout, Carien L. Creutzberg, Ian P.M. Tomlinson, David N. Church, Vincent T.H.B.M. Smit, Niels de Wind, Tjalling Bosse, Mark Drost
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Pathogenic POLE proofreading domain mutations are found in many malignancies where they are associated with ultramutation and favorable prognosis. The extent to which this prognosis depends on their sensitivity to adjuvant treatment is unknown, as is the optimal therapy for advanced-staged or recurrent POLE-mutant cancers. Experimental Design: We examined the recurrence-free survival of women with POLE-mutant and POLE–wild-type endometrial cancers (EC) in the observation arm of the randomized PORTEC-1 endometrial cancer trial (N = 245 patients with stage I endometrial cancer for analysis). Sensitivity to radiotherapy and selected chemotherapeutics was compared between Pole-mutant mouse-derived embryonic stem (mES) cells, generated using CRISPR-Cas9 (Pole mutations D275A/E275A, and cancer-associated P286R, S297F, V411L) and isogenic wild-type cell lines. Results: In the observation arm of the PORTEC-1 trial (N = 245), women with POLE-mutant endometrial cancers (N = 16) had an improved recurrence-free survival (10-year recurrence-free survival 100% vs. 80.1% for POLE–wild-type; HR, 0.143; 95% confidence interval, 0.001–0.996; P = 0.049). Pole mutations did not increase sensitivity to radiotherapy nor to chemotherapeutics in mES cells. In contrast, Pole-mutant cells displayed significantly increased sensitivity to cytarabine and fludarabine (IC50 Pole P286R–mutant vs. wild-type: 0.05 vs. 0.17 μmol/L for cytarabine, 4.62 vs. 11.1 μmol/L for fludarabine; P &amp;lt; 0.001 for both comparisons). Conclusions: The favorable prognosis of POLE-mutant cancers cannot be explained by increased sensitivity to currently used adjuvant treatments. These results support studies exploring minimization of adjuvant therapy for early-stage POLE-mutant cancers, including endometrial and colorectal cancers. Conversely, POLE mutations result in hypersensitivity to nucleoside analogues, suggesting the use of these compounds as a potentially effective targeted treatment for advanced-stage POLE-mutant cancers. Clin Cancer Res; 24(13); 3197–203. ©2018 AACR.
Response to Comments on Santema et al. Hyperbaric Oxygen Therapy in the Treatment of Ischemic Lower-Extremity Ulcers in Patients With Diabetes: Results of the DAMO2CLES Multicenter Randomized Clinical Trial. Diabetes Care 2018;41:112–119
Authors: Katrien T.B. Santema, Robert M. Stoekenbroek, Mark J.W. Koelemay, Dirk T. Ubbink
Journal: Diabetes Care (2018)

We thank Drs. Mutluoglu (1) and Huang (2) for their critical comments. They both express concerns regarding our conclusion based on the results of the DAMO2CLES [Does Applying More Oxygen (O2) Cure Lower Extremity Sores?] trial that hyperbaric oxygen therapy (HBOT) does not confer benefit in the treatment of patients with ischemic foot ulcers and diabetes (3).

During the course of the trial, lagging patient inclusion necessitated a downward adjustment of the sample size to meet the time limit imposed by the sponsor of the trial. Nevertheless, this trial still is the largest trial on HBOT in the treatment of ischemic ulcers and allows for future meta-analysis.

Huang (2) was concerned about the variation in clinical practice. The common treatments for diabetic ischemic foot ulcers, such as wound management, vascular surgery, and total …
Response by O’Byrne et al to Letter Regarding Article, “Effect of Obesity and Underweight Status on Perioperative Outcomes of Congenital Heart Operations in Children, Adolescents, and Young Adults: An Analysis of Data From the Society of Thoracic Surgeons Database”
Authors: Michael L. O’Byrne, Jeffrey P. Jacobs, Marshall L. Jacobs, Richard A. Jonas
Journal: Circulation (2018)
Evidence of Drug-Free Interventions for Postoperative Pain Management After Total Knee Arthroplasty
Authors: Jing-hua Jiao, Lei Liu, Xiao-feng Sun
Journal: JAMA Surgery (2018)

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CLINICAL IMPACT OF IN-HOSPITAL CONDUCTION BLOCKS IN PATIENTS UNDERGOING TRANS-CATHETER AORTIC VALVE REPLACEMENT: ANALYSIS FROM NATIONWIDE INPATIENT SAMPLE DATABASE (NIS)
Authors: Mohit Pahuja, Kinsuk Chauhan, Manmohan Singh, Achint Patel, Tomo Ando, Tushar Mishra, Luis Afonso
Journal: Journal of the American College of Cardiology (2018)
Simultaneous, single cell, flow cytometric quantification of PD-L1/TILs/cell cycle in non-small cell lung cancer tissue biopsies: Concordance of PD-L1 expression detection between flow cytometry and immunohistochemistry.
Authors: Stephen Young, Christen Griego-Fullbright, Aaron Wagner, Amanda Chargin, Bruce Kendrick Patterson
Journal: Journal of Clinical Oncology (2018)

159 Background: Tumor cell expression of PD-L1 leads to the inhibition of immune responses specifically inactivation of cytotoxic T-cells. PD-L1 expression on tumor cells by immunohistochemistry does not provide the complete picture of therapeutic (PD-L1) and prognostic (TILs, aneuploidy) markers. Here, we report a clinical assay that quantifies tumor infiltrating lymphocytes (TILs), cell cycle/DNA content as well as PD-L1 expression on tumor and aneuploid tumor cell populations. Methods: Punch biopsies were taken from 19 fresh tissues specimens and were processed into single cell suspensions using the IVD/CE-IVD IncellPREP Single Cell Preparation Kit. Cells were fixed and permeabilized in 1 mL IncellMax. Cells were tested with the OncoTect iO Lung Assay which contains antibodies directed against PD-L1 (clone 28-8), CD45, CD3, and CD8, and a cell cycle dye. Concordance to IHC was tested by the Dako PD-L1 IHC 28-8 PharmDx Kit. Immune cell populations were quantified and aneuploidy was determined using a DNA index &gt; 1.05. Results: The number of CD8+ CTL were significantly increased (P = 0.02) in tumor compared to normal lung tissue (37.4% to 28.2%). The number of CTL in aneuploid tumors was twice the number of CTL in diploid tumors. The percentage of antigen presenting cells (CD45+, high SSC) was decreased in the tumor cell samples relative to the normal lung tissue (P = 0.01). PD-L1 expression varies in cells depending on the cell cycle. Conclusions: In this study, the concordance between Oncotect iO and IHC was 95% (NPA-97%, PPA-89%). PD-L1 expression varies with DNA content, PD-L1 expression decreases with increasing DNA content. Though CTL are increased in aneuploid tumors, PD-L1 expression decreasing with DNA content may contribute to the association of aneuploidy with distant metastases. PD-L1 expression is a powerful determinant of treatment and aneuploidy is a powerful prognostic factor that combined yield important clinical information.
Abstract P6-15-07: Not presented
Authors: G Somlo, J Waisman, Y Yuan, M Li, L Kruper, V Jones, T Treece, P Frankel, J Yim, L Tumyan, D Schmolze, F Menghi, ET Liu, A Hurria, C Yeon, J Mortimer
Journal: Cancer Research (2018)

Abstract This abstract was not presented at the symposium.
Local Delivery Of Irinotecan To Recurrent Glioblastoma At Reoperation Offers A Safe Therapeutic Advantage Over Systemic Delivery
Authors: Garth Cruickshank, Desire Ngoga, Allah Detta, Andy Lewis, Rebecca Holden, Olufawe Fayaye
Journal: Neuro-Oncology (2018)

Direct drug delivery to a brain tumours offers the surety of access, together with the potential to realise at least therapeutic concentrations. With previously used systemic drugs toxicity and removal mechanisms are avoided. With new formulations drug activation and duration can be explored for low local toxicity, and tumour impact with sequential imaging. In this early study Irinotecan a drug with known efficacy against glioma but with limiting systemic toxicity has been incorporated into biodegradeable hydrogel microspheres and injected into the post-surgical cavity wall in patients with recurrent glioblastoma. 10 patients with focally recurrent GBM were recruited with 9 undergoing injection with up to 3mls of microbeads in alginate suspension in up to 60 ~ 8mm injection tracks after surgical resection (100mg). Patients were assessed for immediate (72hrs) toxicity with clinical assessment and imaging. Pharmacokinetic determination of Irinotecan and SN 38 active metabolite allowed confirmation of activation and comparator with known plasma toxicity profiles. Follow-up was planned for a minimum of 6/12 for SAE but continued to allow overall survival estimation. No overt SAE were determined for this group of patients with imaging and steroid use indicating less local swelling and wound healing issues than have been demonstrated for Carmustine wafers despite early offloading. Phamacokinetic measures (SN38 plasma curves) indicate a much higher activation of Irinotecan (>90%) than expected but shorter period of exposure. Survival curves suggest clinical benefit with 4/9 patient living longer than 8 months warranting further exploration of this safe approach
CHANGE IN LEFT VENTRICULAR SYSTOLIC WALL STRESS PREDICTS HEART FAILURE READMISSIONS IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Nikhil Agrawal, Abhishek Sawant, Aishwarya Bhardwaj, Thammi Ramanan, Rosemary Hansen, Everett Sinibaldi, Priya Sadawarte, Ankush Lahoti, Arnav Kumar, Kimi Sato, Kalaimani Elango, Tanvi Shah, Stanley Fernandez, Umesh Sharma, Vijay Iyer
Journal: Journal of the American College of Cardiology (2018)
The COMMD Family Regulates Plasma LDL Levels and Attenuates Atherosclerosis Through Stabilizing the CCC Complex in Endosomal LDLR Trafficking
Authors: Alina Fedoseienko, Melinde Wijers, Justina C. Wolters, Daphne Dekker, Marieke Smit, Nicolette Huijkman, Niels Kloosterhuis, Helene Klug, Aloys Schepers, Ko Willems van Dijk, Johannes H.M. Levels, Daniel D. Billadeau, Marten H. Hofker, Jan van Deursen, Marit Westerterp, Ezra Burstein, Jan Albert Kuivenhoven, Bart van de Sluis
Journal: Circulation Research (2018)

Rationale: COMMD (copper metabolism MURR1 domain)-containing proteins are a part of the CCC (COMMD–CCDC22 [coiled-coil domain containing 22]–CCDC93 [coiled-coil domain containing 93]) complex facilitating endosomal trafficking of cell surface receptors. Hepatic COMMD1 inactivation decreases CCDC22 and CCDC93 protein levels, impairs the recycling of the LDLR (low-density lipoprotein receptor), and increases plasma low-density lipoprotein cholesterol levels in mice. However, whether any of the other COMMD members function similarly as COMMD1 and whether perturbation in the CCC complex promotes atherogenesis remain unclear. Objective: The main aim of this study is to unravel the contribution of evolutionarily conserved COMMD proteins to plasma lipoprotein levels and atherogenesis. Methods and Results: Using liver-specific Commd1 , Commd6 , or Commd9 knockout mice, we investigated the relation between the COMMD proteins in the regulation of plasma cholesterol levels. Combining biochemical and quantitative targeted proteomic approaches, we found that hepatic COMMD1, COMMD6, or COMMD9 deficiency resulted in massive reduction in the protein levels of all 10 COMMDs. This decrease in COMMD protein levels coincided with destabilizing of the core (CCDC22, CCDC93, and chromosome 16 open reading frame 62 [C16orf62]) of the CCC complex, reduced cell surface levels of LDLR and LRP1 (LDLR-related protein 1), followed by increased plasma low-density lipoprotein cholesterol levels. To assess the direct contribution of the CCC core in the regulation of plasma cholesterol levels, Ccdc22 was deleted in mouse livers via CRISPR/Cas9-mediated somatic gene editing. CCDC22 deficiency also destabilized the complete CCC complex and resulted in elevated plasma low-density lipoprotein cholesterol levels. Finally, we found that hepatic disruption of the CCC complex exacerbates dyslipidemia and atherosclerosis in ApoE3*Leiden mice. Conclusions: Collectively, these findings demonstrate a strong interrelationship between COMMD proteins and the core of the CCC complex in endosomal LDLR trafficking. Hepatic disruption of either of these CCC components causes hypercholesterolemia and exacerbates atherosclerosis. Our results indicate that not only COMMD1 but all other COMMDs and CCC components may be potential targets for modulating plasma lipid levels in humans.
I trained in general practice but I am currently a full time mother. I have no plans to return to medical work for at least five years. What should I be doing about revalidation?
Authors: Brian Keighley
Journal: BMJ (2004)

Cryo-electron tomography (cryo-ET) allows for the high resolution visualization of biological macromolecules. However, the technique is limited by a low signal-to-noise ratio (SNR) and variance in contrast at different frequencies, as well as reduced Z resolution. Here, we applied entropy regularized deconvolution (ER DC) to cryo-electron tomography data generated from transmission electron microscopy (TEM) and reconstructed using weighted back projection (WBP). We applied DC to several <i>in situ</i> cryo-ET data sets, and assess the results by Fourier analysis and subtomogram analysis (STA).
Comment on Jaiswal et al. Prevalence of and Risk Factors for Diabetic Peripheral Neuropathy in Youth With Type 1 and Type 2 Diabetes: SEARCH for Diabetes in Youth Study. Diabetes Care 2017;40:1226–1232
Authors: Amélie Simoneau, Marie Monlun, Pauline Poupon, Laurence Baillet-Blanco, Laure Alexandre, Kamel Mohammedi, Vincent Rigalleau
Journal: Diabetes Care (2018)

We were interested by the recent article by Jaiswal et al. (1), who reported a high prevalence (22%) of diabetic peripheral neuropathy (DPN) in young subjects with type 2 diabetes in the SEARCH for Diabetes in Youth (SEARCH) study. Although significance was not reached for all the analyses in the type 2 diabetes group, long-term poor glycemic control, dyslipidemia, and smoking emerged as modifiable risk factors, and the authors suggested that their management may help to prevent or delay irreversible nerve damage. This optimistic view is, however, challenged by the results of multifactorial interventions: no improvement of vibration perception thresholds (VPT) in the Steno-2 study (2) and only a small initial improvement with later seemingly inexorable progression …
Molecular Lymph Node Status for Prognostic Stratification of Prostate Cancer Patients Undergoing Radical Prostatectomy with Extended Pelvic Lymph Node Dissection
Authors: Matthias M. Heck, Margitta Retz, Miriam Bandur, Marc Souchay, Elisabeth Vitzthum, Gregor Weirich, Tibor Schuster, Michael Autenrieth, Hubert Kübler, Tobias Maurer, Mark Thalgott, Kathleen Herkommer, Jürgen E. Gschwend, Roman Nawroth
Journal: Clinical Cancer Research (2018)

Purpose: Molecular lymph node (LN) analysis using quantitative polymerase chain reaction (qPCR) detects LN metastases with higher sensitivity than histopathology. However, the prognostic role of molecular LN status in prostate cancer patients treated with radical prostatectomy (RP) and extended pelvic LN dissection (ePLND) is unclear. To investigate the association of molecular compared with histopathologic LN status with biochemical recurrence.Experimental Design: Patients with intermediate and high-risk prostate cancer were prospectively enrolled and underwent RP with ePLND, including the obturator, internal, external, and the common iliac region. LNs ≥3 mm were bisected and examined by standard histopathology and qPCR for Kallikrein3 (KLK3) expression. Biochemical recurrence was defined by confirmed postoperative PSA > 0.2 ng/mL.Results: In 111 patients, 2,411 of 3,173 removed LNs were examined by both methods. Histopathology detected 68 LN metastases in 28 (25%) patients. Molecular analysis confirmed elevated KLK3 expression in 65 histopathologic LN metastases of all 28 pN1 patients (pN1/molN1) and additionally reclassified 224 histopathologic negative LNs and 32 (29%) pN0 patients as LN-positive (pN0/molN1).At a median follow-up of 48 months, 52 (47%) patients developed biochemical recurrence. Median biochemical recurrence-free survival was 9 months [95% confidence interval (CI), 0.0-20.1] in pN1/molN1 patients, 24 months (95% CI, 1.7-46.3) in pN0/molN1 patients and was not reached in pN0/molN0 patients (P < 0.001). On multivariable Cox regression analysis, molecular LN status [HR 4.1 (95% CI, 1.9-8.8), P < 0.001] but not histopathologic LN status [HR 1.5 (95% CI, 0.8-3.0), P = 0.198] was confirmed as independent predictor of biochemical recurrence.Conclusions: Molecular LN analysis identified pN0 patients with a high risk of biochemical recurrence and provided superior prognostic information in comparison with histopathology alone. Clin Cancer Res; 24(10); 2342-9. ©2018 AACR.
Health care resource utilization and costs in metastatic castration-resistant prostate cancer patients treated with enzalutamide or abiraterone acetate.
Authors: Vahan Kassabian, Scott Flanders, Samuel Wilson, Bruce A. Brown, Yan Song, Hongbo Yang, Stanislav Lechpammer, Neil M. Schultz
Journal: Journal of Clinical Oncology (2018)

232 Background: Cost of care is an important component of valuation of novel treatments in oncology. Enzalutamide (ENZA) and abiraterone acetate (ABI) are approved hormonal agents for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study compared healthcare resource utilization (HRU) and costs for patients treated with ENZA or ABI in the U.S. Methods: Adult mCRPC patients initiating ENZA or ABI before and or after cytotoxic chemotherapy were identified from the Truven MarketScan claims database (2012–2015). The first claim of ENZA or ABI was defined as the index date; continuous enrollment ≥6 months before and ≥3 months after the index date was required. HRU and costs were estimated during the post-index period for both cohorts. Generalized linear models compared HRU and costs between the cohorts and were adjusted for baseline demographic and clinical covariates. Analyses were separately conducted for chemo-naïve and chemo-experienced patients. Results: The study included 3230 chemo-naive patients (ENZA 920; ABI 2310) and 692 chemo-experienced patients (ENZA 262; ABI 430). Among chemo-naive patients, ENZA cohort was older (mean age: 74.5 vs 73.5; p=0.013), with a higher proportion of baseline comorbidities vs ABI cohort. During the post-index period, ENZA cohort had fewer all-cause inpatient admissions (IPA) [adjusted incidence rate ratio (IRR) 0.87; p=0.033], all-cause outpatient visits (OPV) [adjusted IRR 0.94; p=0.004], and PC-related OPV (adjusted IRR 0.92; p&lt;0.001) vs the ABI cohort. Within 3 months of the index date, ENZA cohort was less likely to have an all-cause IPA (adjusted odds ratio [OR] 0.75; p=0.029). In addition, ENZA cohort had lower PC-related IPA and emergency department (ED) costs vs ABI cohort. The differences of HRU and medical costs between the 2 cohorts were not statistically significant for chemo-experienced patients. Conclusions: Despite a higher comorbidity burden at baseline, chemo-naive mCRPC patients treated with ENZA incurred less HRU and lower PC-related IPA and ED costs vs ABI cohort. Differences between the 2 cohorts were not statistically significant for chemo-experienced patients.
Prevalence of Self-Reported Hypertension and Antihypertensive Medication Use Among Adults Aged ≥18 Years — United States, 2011–2015
Authors: Jing Fang, Cathleen Gillespie, Carma Ayala, Fleetwood Loustalot
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Hypertension, which affects nearly one third of adults in the United States, is a major risk factor for heart disease and stroke (1), and only approximately half of those with hypertension have their hypertension under control (2). The prevalence of hypertension is highest among non-Hispanic blacks, whereas the prevalence of antihypertensive medication use is lowest among Hispanics (1). Geographic variations have also been identified: a recent report indicated that the Southern region of the United States had the highest prevalence of hypertension as well as the highest prevalence of medication use (3). Using data from the Behavioral Risk Factor Surveillance System (BRFSS), this study found minimal change in state-level prevalence of hypertension awareness and treatment among U.S. adults during the first half of the current decade. From 2011 to 2015, the age-standardized prevalence of self-reported hypertension decreased slightly, from 30.1% to 29.8% (p = 0.031); among those with hypertension, the age-standardized prevalence of medication use also decreased slightly, from 63.0% to 61.8% (p<0.001). Persistent differences were observed by age, sex, race/ethnicity, level of education, and state of residence. Increasing hypertension awareness, as well as increasing hypertension control through lifestyle changes and consistent antihypertensive medication use, requires diverse clinical and public health intervention.