tbuckley/cabot-search huggingface dataset:
Medical manslaughter: independent review calls for root and branch reform of cases
Authors: Clare Dyer
Journal: BMJ (2019)

An independent review of medical manslaughter cases in the UK has called for root and branch reforms, ranging from local investigations to regulatory action by the General Medical Council (GMC), to ensure a “learning not blame” culture that is fair to patients and doctors.1

The review was chaired by Leslie Hamilton, a cardiac surgeon, and was commissioned by the GMC after the case of the paediatric trainee Hadiza Bawa-Garba sent shockwaves through the profession.

“Doctors were suddenly afraid,” said Hamilton. “It was described as a toxic fear spreading through the profession.”

Bawa-Garba was convicted of gross negligence manslaughter over the death of 6 year old Jack Adcock and given a two year suspended sentence. She was suspended from practice for 12 months by a medical practitioners tribunal, but the GMC appealed to the High Court, which struck her off the medical register. Bawa-Garba took her case to the Court of Appeal, which reinstated her to the register.2

Hamilton commented, “What …
帮助患者通过自我检查早期检测皮肤癌的干预的效果:一项系统回顾、元分析
Authors: S.J. Ersser, A. Effah, J. Dyson, I. Kellar, S. Thomas, E. McNichol, E. Caperon, C. Hewitt, A.J. Muinonen‐Martin
Journal: British Journal of Dermatology (2019)

皮肤癌患者在许多国家不断增多(包括英国)。例如,2017 年,在美国 87,000 多人被诊断患有危险性皮肤癌症(黑色素瘤);其中预计近10,000名患者死于该疾病。我们这个英国研究团队对全世界的科学论文进行了回顾。我们目的在于分析和汇总有关帮助患者自我检查皮肤以早期检测皮肤癌的不同方法是否有效的现有研究。本次回顾确认了截至 2018 年4月已知研究发布的所有相关论文。这些确认的相关研究共计 18项,我们对其进行了汇总。上述方法包括教育,例如,教导和提醒患者(有时利用技术,如使用计算机和手机)检查皮肤,并向医生快速报告任何疑似改变。我们发现所用的各种方法都对患者检查皮肤的可能性和能力具有积极影响,尤其是在短期内。更多研究是针对面临更高皮肤癌风险的患者(如既往皮肤癌患者),而非无更大风险的患者。在我们分析的研究中,2/3研究设计不佳。皮肤专科医生应该提高认识并帮助患者定期检查皮肤以检测皮肤癌,尤其是高危患者。
Reversing tumor stemness via orally targeted nanoparticles achieves efficient colon cancer treatment
Authors: Jiaqi Xu, Yinlong Zhang, Junchao Xu, Meifang Wang, Guangna Liu, Jing Wang, Xiao Zhao, Yingqiu Qi, Jian Shi, Keman Cheng, Yao Li, Sheng Qi, Guangjun Nie
Journal: Biomaterials (2019)
Mouse CD19-Targeted Chimeric Antigen Receptors That Include a 41BB Co-Stimulatory Domain Induce NFkB Signaling to Enhance T Cell Proliferation, Viability, and Leukemia Killing
Authors: Gongbo Li, Nolan Beatty, Paresh Vishwasrao, Justin C. Boucher, Bin Yu, Kyungho Park, Yongliang Zhang, Marco L. Davila
Journal: Blood (2017)
Endoscopic removal of tubulovillous adenoma with high grade focal dysplasia in the distal common bile duct
Authors: Rogger Alvaro Bendezú-García, Xavier Andújar-Murcia, Carme Loras
Journal: Endoscopy (2019)

An 80-year-old woman with pluripathology was admitted with cholangitis. A computed tomography scan showed a dilated common bile duct (CBD) and a possible distal choledocholithiasis. An endoscopic retrograde cholangiopancreatography was performed and the duct was swept with a balloon, revealing a polypoid lesion of adenomatous appearance through the papilla. The pathology confirmed a tubulo-villous adenoma with high grade focal dysplasia. An endoscopic ultrasound revealed the presence of a 10 × 8 mm polyp in the CBD ([Fig. 1]). As the patient was a high risk surgical candidate, endoscopic treatment was indicated in accordance with a multidisciplinary committee.
Abstract 173: Coronary artery aneurysm measurement and z-score variability in Kawasaki Disease
Authors: Christina Ronai, Akiko Hamaoka-Okamoto, Christian Stopp, Jane W Newburger, Kevin Friedman
Journal: Circulation (2015)

Background: Coronary artery (CA) z-scores are commonly used for clinical decisions in Kawasaki disease (KD). We evaluated reliability in CA measurement, reproducibility of z-score calculation, and frequency with which different z-score formulas lead to divergent management strategies. Methods: We randomly selected 21 KD patients (pts) with ≥1 CA z-score 1.5-3 and all KD pts with ≥ 1 CA z-score 7-14 (n=20). Two echocardiographers measured LMCA, LAD and RCA. Inter- and intraobserver reliability were calculated. T-tests were used to compare CA z-score using 3 commonly used formulas (Boston, DC and Montreal). Results: Median age at KD echo was 1.2 y (0.2-11.5 y). Interobserver reliability was high for LAD (intraclass correlation [ICC] 0.970) and RCA (ICC 0.943) and lower for LMCA (ICC 0.725). Intraobserver reliability was also high for LAD and RCA (ICC 0.991 and 0.999) and lower for LMCA (ICC 0.946). Z-scores for the 3 formulas were similar at smaller CA size, i.e., z &lt; 3, but varied markedly at larger CA dimensions (Figure). Z-scores for the same CA dimension calculated by each of the 3 formulas resulted in disparate classification of normal vs. mild dilation in 7/21 (22%) pts, and different guidance for anticoagulation based on CA z ≥10 in 10/20 (50%) pts. Conclusion: Although CA measurements have high inter- and intraobserver agreement, CA z-scores vary dramatically based on the z-score formula, particularly at larger CA dimensions. Discrepancies in CA z-score between calculators impacts not only the distinction between normal and mild dilatation, but most importantly, the recommendation of anticoagulation for pts with larger CA dimensions.
Effect of Early Limited Formula on Breastfeeding Duration in the First Year of Life
Authors: Valerie J. Flaherman, Michael D. Cabana, Charles E. McCulloch, Ian M. Paul
Journal: JAMA Pediatrics (2019)

Breastfeeding through 6 and 12 months are 2 goals of the Centers for Disease Control and Prevention Healthy People 2020 initiative, but the 6-month goal is met for only 52% of US infants and the 12-month goal for 30% of US infants.To determine whether structured, short-term formula supplementation for at-risk neonates affects the proportion still breastfeeding at 6 and 12 months.This randomized clinical trial conducted at 2 US academic medical centers enrolled 164 exclusively breastfeeding mother-infant dyads of mothers who were not yet producing copious milk and infants who were 24 to 72 hours old with newborn weight loss at or above the 75th percentile for age. Participants were enrolled from January 2015 through September 2016.Early Limited Formula (ELF), a structured formula supplementation protocol (10 mL formula fed after each breastfeeding until mothers produced copious milk), compared with control dyads, who continued exclusive breastfeeding and received a safety teaching intervention.The study's primary outcome was any breastfeeding at 6 months. Secondary outcomes included age at breastfeeding cessation and any breastfeeding at 12 months. All outcomes were assessed by maternal phone survey.Eighty-two newborns were randomized to ELF and 82 to the control group. Mean (SD) maternal age was 31.4 (5.9) years, and 114 (69.5%) self-identified as non-Hispanic white; 20 (12.2%), Hispanic; 17 (10.4%), Asian; 5 (3.0%), non-Hispanic black; and 7 (4.3%), other. Compared with controls, mothers randomized to ELF were less likely to be married (n = 53 [64.6%] vs n = 66 [80.5%]; P = .03) and had shorter mean (SD) intended duration of breastfeeding (8.6 [3.4] vs 9.9 [4.4] months; P = .049). Median (interquartile range) duration of breastfeeding in the cohort was 9 (6-12) months. At 6 months, 47 (65%) infants randomized to ELF were breastfeeding, compared with 60 (77%) of the control infants (absolute difference, -12%; 95% CI, -26% to 3%; P = .12). At 12 months, 21 of the 71 ELF infants available for analysis (29.6%) were breastfeeding, compared with 37 of the available 77 (48.1%) control infants (risk difference, -18%; 95% CI, -34% to -3%). Marital status and intended breastfeeding duration were both associated with breastfeeding duration; models adjusting for these found a hazard ratio for time-to-event of breastfeeding cessation through 12 months of 0.74 (95% CI, 0.48-1.14) for ELF infants compared with infants in the control group.In this cohort with high breastfeeding prevalence, ELF was not associated with any improvement in breastfeeding duration. Future research should examine the effect of ELF in populations at higher risk of early cessation.ClinicalTrials.gov identifier: NCT02313181.
Abstract 13297: Short-Term Mortality in Patients With Myocardial Injury and Myocardial Infarction Type 1 and Type 2
Authors: Laura Sarkisian, Lotte Saaby, Tina S Poulsen, Oke Gerke, Axel C Diederichsen, Nikolaj Jangaard, Susanne Hosbond, Kristian Thygesen, Hans Mickley
Journal: Circulation (2015)

Introduction: Troponin elevations occur in a myriad of clinical conditions other than myocardial infarction (MI) and imply a poor prognosis. So far, data comparing the short-term outcome in patients with myocardial injury vs. patients with type 1 or type 2 MI are not available. Methods: Over a 1-year period we prospectively studied hospitalized patients having cardiac troponin I (cTnI) measured on clinical indication. The diagnosis of type 1 and type 2 MI was according to the universal definition involving a rising and/or falling pattern of cTnI values above the decision limit of 30 ng/L. cTnI elevations above this limit in patients without overt myocardial ischemia were defined as myocardial injury. A 1-month follow-up was done with mortality as endpoint. Results: The study covered 1577 consecutive patients with cTnI values &gt;30 ng/L, of whom 360 had a type 1 MI, 119 a type 2 MI and 1089 had myocardial injury. Type 1 MI patients were younger with a median age of 70 (IQR 61-81) yrs, whereas the median ages in type 2 MI and myocardial injury were higher but comparable : 78 (IQR 67-84) vs. 77 (IQR 67-85) yrs. Peak cTnI values, however, were highest in type 1 MI: 3820 (530-19030) ng/L, lower in type 2 MI: 850 (390-3270) ng/L, and smallest in patients with myocardial injury: 90 (50-270) ng/L (p=0.0001). At one-month follow-up 285 patients had died. Mortality in the different subgroups was: 9% (33/360) in type 1 MI, 24% (28/119) in type 2 MI, and 21% (224/1089) in patients with myocardial injury. The results are depicted in the figure (Kaplan-Meier curves, log-rank-test; p-value &lt;0.0001). Multivariate COX regression analysis revealed a Hazard Ratio (95%) of 2.1 (1.2-3.7) for type 2 MI and 1.4 (0.9-2.1) for myocardial injury. Conclusion: The short-term mortality in patients with myocardial injury and type 2 MI is almost identical but higher than in patients with type 1 MI. These prognostic findings imply that the clinical distinction between myocardial injury and type 2 MI may be somewhat artificial.
Author Correction: Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity
Authors: Tomokazu Sumida, Matthew R. Lincoln, Chinonso M. Ukeje, Donald M. Rodriguez, Hiroshi Akazawa, Tetsuo Noda, Atsuhiko T. Naito, Issei Komuro, Margarita Dominguez-Villar, David A. Hafler
Journal: Nature Immunology (2019)
Pulmonary type-2 innate lymphoid cells in paediatric severe asthma: phenotype and response to steroids
Authors: Prasad Nagakumar, Franz Puttur, Lisa G. Gregory, Laura Denney, Louise Fleming, Andrew Bush, Clare M. Lloyd, Sejal Saglani
Journal: European Respiratory Journal (2019)

Children with severe therapy-resistant asthma (STRA) have poor control despite maximal treatment, while those with difficult asthma (DA) have poor control from failure to implement basic management, including adherence to therapy. Although recognised as clinically distinct, the airway molecular phenotype, including the role of innate lymphoid cells (ILCs) and their response to steroids in DA and STRA is unknown. Immunophenotyping of sputum and blood ILCs and T-cells from STRA, DA and non-asthmatic controls was undertaken. Leukocytes were analysed longitudinally pre- and post-intramuscular triamcinolone in children with STRA. Cultured ILCs were evaluated to assess steroid responsiveness in vitro . Airway eosinophils, type 2 T-helper (Th2) cells and ILC2s were significantly higher in STRA patients compared to DA and disease controls, while IL-17 + lymphoid cells were similar. ILC2s and Th2 cells were significantly reduced in vivo following intramuscular triamcinolone and in vitro with steroids. Furthermore, asthma attacks and symptoms reduced after systemic steroids despite persistence of steroid-resistant IL-17 + cells and eosinophils. Paediatric STRA and DA have distinct airway molecular phenotypes with STRA characterised by elevated type-2 cells. Systemic corticosteroids, but not maintenance inhaled steroids resulted in improved symptom control and exacerbations concomitant with a reduction in functional ILC2s despite persistently elevated IL-17 + lymphoid cells.
Is the duration of adjuvant trastuzumab debate still clinically relevant?
Authors: Sara A Hurvitz
Journal: The Lancet (2019)

The selection of optimal systemic therapy for early HER2-positive breast cancer has become exceedingly complex. Since the advent of adjuvant trastuzumab, several new drugs have shown substantial incremental benefits.1–4 Clearly, not all patients should receive these additional therapies. Hence, it is incumbent upon clinicians to carefully select patients who are the most likely to benefit from an escalation strategy. To this end, progress is being made. For example, the recognition that poor response to neoadjuvant therapy is associated with poor outcomes in HER2-positive disease led to the design of the KATHERINE study,5 in which patients with residual disease after neoadjuvant therapy received adjuvant trastuzumab-emtansine or standard trastuzumab.
BMI, Weight Change, and Dementia Risk in Patients With New-Onset Type 2 Diabetes: A Nationwide Cohort Study
Authors: Ga Eun Nam, Yong Gyu Park, Kyungdo Han, Mee Kyoung Kim, Eun Sil Koh, Eun Sook Kim, Min-Kyung Lee, Bongsung Kim, Oak-Kee Hong, Hyuk-Sang Kwon
Journal: Diabetes Care (2019)

This study examined the association between baseline BMI, percentage weight change, and the risk of dementia in patients newly diagnosed with type 2 diabetes.Using the South Korean National Health Insurance Service-National Health Screening Cohort database, we identified 167,876 subjects aged ≥40 years diagnosed with new-onset type 2 diabetes between 2007 and 2012. Their weight changes were monitored for ∼2 years after diagnosis, with follow-up assessments occurring for an average of 3.5 years. The hazard ratios (HRs) and Bonferroni-adjusted 95% CIs of all-cause dementia, Alzheimer disease (AD), and vascular dementia were estimated using multivariable Cox proportional hazards regression models.We identified 2,563 incident dementia cases during follow-up. Baseline BMI among patients with new-onset type 2 diabetes was inversely associated with the risk of all-cause dementia and AD, independent of confounding variables (P for trend <0.001). The percentage weight change during the 2 years after a diagnosis of type 2 diabetes showed significant U-shaped associations with the risk of all-cause dementia development (P < 0.001); the HRs of the disease increased significantly when weight loss or gain was >10% (1.34 [95% CI 1.11-1.63] and 1.38 [1.08-1.76], respectively). Additionally, weight loss >10% was associated with an increased risk of AD (HR 1.26 [95% CI 1.01-1.59]).A lower baseline BMI was associated with increased risks of all-cause dementia and AD in patients with new-onset type 2 diabetes. Weight loss or weight gain after the diagnosis of diabetes was associated with an increased risk of all-cause dementia. Weight loss was associated with an increased risk of AD.
Age Mosaicism across Multiple Scales in Adult Tissues
Authors: Rafael Arrojo e Drigo, Varda Lev-Ram, Swati Tyagi, Ranjan Ramachandra, Thomas Deerinck, Eric Bushong, Sebastien Phan, Victoria Orphan, Claude Lechene, Mark H. Ellisman, Martin W. Hetzer
Journal: Cell Metabolism (2019)
Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001.
Authors: Edward B. Garon, Matthew David Hellmann, Enric Carcereny Costa, Natasha B. Leighl, Myung-Ju Ahn, Joseph Paul Eder, Ani Sarkis Balmanoukian, Charu Aggarwal, Leora Horn, Amita Patnaik, Matthew A. Gubens, Suresh S. Ramalingam, Enriqueta Felip, Cathie Scalzo, Erin Jensen, Debra A. Kush, Rina Hui
Journal: Journal of Clinical Oncology (2019)

LBA9015 Background: Pembrolizumab (pembro) monotherapy has demonstrated durable antitumor activity in advanced PD-L1–expressing NSCLC. We present 5-y OS for patients (pts) enrolled in the phase 1b KEYNOTE-001 study (NCT01295827), the first trial evaluating pembro in advanced NSCLC. These data provide the longest efficacy/safety follow-up for NSCLC pts treated with pembro. Methods: Pts had confirmed locally advanced/metastatic NSCLC and provided a contemporaneous tumor sample for PD-L1 evaluation by IHC using the 22C3 antibody. Pts received pembro 2 mg/kg Q3W or 10 mg/kg Q2W or Q3W. The primary efficacy endpoint was ORR. OS was a secondary endpoint. Results: 550 pts were enrolled (treatment-naive, n=101; previously treated, n=449). As of November 5, 2018 (data cutoff), median (range) follow-up was 60.6 (51.8–77.9) mo; 82% (n=450/550) had died. Estimated 5-y OS rates were 23.2% for treatment-naive pts and 15.5% for previously treated pts (Table). ORR (by investigator per irRC) was 42% (95% CI, 32–52) for treatment-naive pts and 23% (95% CI, 19–27) for previously treated pts. Median (range) DOR was 16.8 (2.1+ to 55.7+) mo and 38.9 (1.0+ to 71.8+) mo, respectively. Immune-mediated AEs had occurred in 17% of pts at 5 y, similar to the incidence reported at 3-y follow-up. Additional results, including outcomes in key subgroups and detailed safety follow-up data, will be presented. Conclusions: In KEYNOTE-001, 5-y OS rate was 23.2% in treatment-naive pts and 15.5% in previously treated pts with advanced NSCLC treated with pembro, compared to a historical rate of ~5% (per SEER 2008–2014), prior to the introduction of anti–PD-1 therapy. 5-y OS rate was at least 25% in pts with PD-L1 TPS ≥50% in both pt populations in KEYNOTE-001. Clinical trial information: NCT01295827. [Table: see text]
Evaluation of the NCCN-IPI As a Prognostic Tool in PTCLs
Authors: Fredrik Ellin, Matthew J Maurer, Line Srour, Umar Farooq, Mats Jerkeman, Joseph M Connors, Karin E Smedby, Nabila Nora Bennani, Stephen M Ansell, Graham W Slack, James R. Cerhan, Thomas Relander, Andrew L Feldman, Kerry J Savage
Journal: Blood (2017)
Molecular analysis of the RbBP6 in hepatocellular carcinoma
Authors: Zukile Mbita, Zodwa L. Dlamini
Journal: Cancer Research (2006)

130  RbBP6 is an apoptotic related gene that promises to have a key role in apoptosis and cancer progression. It has been documented by Scot and colleagues that RbBP6 is definitely involved mitotic apoptosis. RbBP6 gene product has been shown to interact with the two most important tumor suppressors, pRb and p53. The fact that RbBP6 can interact with tumor suppressors makes it an interesting gene in regard to cancer. The aim of this study was to determine mutations in RbBP6 domains i.e. Rb- and p53-binding domains. The aim was also to determine the expression of the gene in hepatocellular carcinoma. Hepatocellular carcinoma cell line, HepG2 and hepatocellular carcinoma tissue arrays were used for this study. Extracted RNA from HepG2 cells fibroblasts was used for cDNA synthesis, in which the resultant cDNA was for PCR for mutational analysis and Real-time PCR for quantitative analysis. Cells were also fixed on the cover slips for both FISH and immunocytochemistry for expression pattern and expression levels at mRNA and protein levels respectively. Apoptosis was induced in HepG2 cells using staurosporine and RbBP6 expression was analyzed using Real-time PCR. Preliminary results on Rb- and p53-binding domains of the RbBP6 showed no mutations in HepG2 cells. This may mean that RbBP6 binding to Rb and p53 is not affected in hepatocellular carcinoma. More hepatocellular carcinoma cell lines need to be screened. Tissue arrays of hepatocellular carcinoma has demonstrated that the gene localizes in the cytoplasm in the cancer cases while in the normal, there were traces of nuclear localization both at the mRNA and protein level. RbBP6 was only expressed at the site where apoptosis was detected. Real-time PCR has confirmed down-regulation of RbBP6 in liver cancer. These results suggest that RbBP6 is a pro-apoptotic gene since its down-regulation correlate with low levels of apoptosis. When apoptosis is induced RbBP6 expression is attenuated which suggests that this gene is one of the key players in apoptotic pathways. They also suggest that it9s binding to pRb and p53 is not affected which suggests that it9s binding to the two tumor suppressors may be required for other processes other than apoptosis.
Increasing Transparency at the US Food and Drug Administration
Authors: Robert Steinbrook
Journal: JAMA Internal Medicine (2019)

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To randomize, or not to randomize, that is the question: using data from prior clinical trials to guide future designs
Authors: Alyssa M Vanderbeek, Steffen Ventz, Rifaquat Rahman, Geoffrey Fell, Timothy F Cloughesy, Patrick Y Wen, Lorenzo Trippa, Brian M Alexander
Journal: Neuro-Oncology (2019)

Understanding the value of randomization is critical in designing clinical trials. Here, we introduce a simple and interpretable quantitative method to compare randomized designs versus single-arm designs using indication-specific parameters derived from the literature. We demonstrate the approach through application to phase II trials in newly diagnosed glioblastoma (ndGBM).We abstracted data from prior ndGBM trials and derived relevant parameters to compare phase II randomized controlled trials (RCTs) and single-arm designs within a quantitative framework. Parameters included in our model were (i) the variability of the primary endpoint distributions across studies, (ii) potential for incorrectly specifying the single-arm trial's benchmark, and (iii) the hypothesized effect size. Strengths and weaknesses of RCT and single-arm designs were quantified by various metrics, including power and false positive error rates.We applied our method to show that RCTs should be preferred to single-arm trials for evaluating overall survival in ndGBM patients based on parameters estimated from prior trials. More generally, for a given effect size, the utility of randomization compared with single-arm designs is highly dependent on (i) interstudy variability of the outcome distributions and (ii) potential errors in selecting standard of care efficacy estimates for single-arm studies.A quantitative framework using historical data is useful in understanding the utility of randomization in designing prospective trials. For typical phase II ndGBM trials using overall survival as the primary endpoint, randomization should be preferred over single-arm designs.