tbuckley/cabot-search huggingface dataset:
Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019
Authors: Pedro Pimentel-Nunes, Diogo Libânio, Ricardo Marcos-Pinto, Miguel Areia, Marcis Leja, Gianluca Esposito, Monica Garrido, Ilze Kikuste, Francis Megraud, Tamara Matysiak-Budnik, Bruno Annibale, Jean-Marc Dumonceau, Rita Barros, Jean-François Fléjou, Fátima Carneiro, Jeanin van Hooft, Ernst Kuipers, Mario Dinis-Ribeiro
Journal: Endoscopy (2019)

Main Recommendations Patients with chronic atrophic gastritis or intestinal metaplasia (IM) are at risk for gastric adenocarcinoma. This underscores the importance of diagnosis and risk stratification for these patients. High definition endoscopy with chromoendoscopy (CE) is better than high definition white-light endoscopy alone for this purpose. Virtual CE can guide biopsies for staging atrophic and metaplastic changes and can target neoplastic lesions. Biopsies should be taken from at least two topographic sites (antrum and corpus) and labelled in two separate vials. For patients with mild to moderate atrophy restricted to the antrum there is no evidence to recommend surveillance. In patients with IM at a single location but with a family history of gastric cancer, incomplete IM, or persistent Helicobacter pylori gastritis, endoscopic surveillance with CE and guided biopsies may be considered in 3 years. Patients with advanced stages of atrophic gastritis should be followed up with a high quality endoscopy every 3 years. In patients with dysplasia, in the absence of an endoscopically defined lesion, immediate high quality endoscopic reassessment with CE is recommended. Patients with an endoscopically visible lesion harboring low or high grade dysplasia or carcinoma should undergo staging and treatment. H. pylori eradication heals nonatrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions, and it is recommended. H. pylori eradication is also recommended for patients with neoplasia after endoscopic therapy. In intermediate to high risk regions, identification and surveillance of patients with precancerous gastric conditions is cost-effective.
Women with breast and uterine cancer in relation to genetic mutation risk: A case-control analysis.
Authors: Michael R. Milam, Michael Stany, Shuwei Li, Kelly Fulk, Elizabeth Chao, Holly Laduca
Journal: Journal of Clinical Oncology (2015)

1549 Background: The purpose of this study is to explore the mutation spectrum and prevalence among women with breast and uterine cancer (BUC) who were clinician-referred for multi-gene panel testing. Methods: Clinical histories for patients who underwent multi-gene panel testing at a single commercial laboratory (Ambry Genetics, Aliso Viejo, CA) were retrospectively reviewed to select cases with a history of both breast and uterine cancer. Patients underwent comprehensive analysis of 6-28 genes, depending on the panel ordered. Gene-specific mutation frequencies were calculated and compared with age- and ethnicity-matched female controls with no reported personal cancer history that were also referred for multi-gene panel testing. Fisher’s exact tests were used to compare categorical variables, and Wilcoxon rank-sum tests were used to compare continuous variables between the 2 groups. Results: 319 women with BUC were identified from March 2012 to June 2014. Approximately 13% (n=42) of BUC patients were found to have gene mutations. The majority of the patients were Caucasian (80.6%; 257/319). The average age at first breast cancer diagnosis was 54 years (range 22-82 years) and the average age at uterine cancer diagnosis was 56 years (range 24-87 years). Analysis of gene-specific mutation frequencies revealed that mutations in BRCA2, MSH6, and PTEN were more frequent among cases than controls. Conclusions: In this multi-gene panel testing analysis, women with BUC are at greater risk of mutations in genes associated with Lynch Syndrome, Cowden Syndrome, and Hereditary Breast and Ovarian Cancer Syndrome. Further study is needed to explore these potential links and expanded genetic testing of breast and uterine cancer patients should be considered. Gene Mutation Frequency Fisher’s Exact Results Cases Controls Odds Ratio (95% CI) 95% CI P-value BRCA1 1.4% 1.4% 1.04 [0.2,3.46] 1 BRCA2 3.8% 1.0% 4.02 [1.48, 9.97] 0.003* CDH1 0.4% 0.1% 3.83 [0.07,73.65] 0.31 MLH1 0.6% 0.1% 4.99 [0.06,391.67] 0.31 MSH2 0.6% 0.1% 4.99 [0.063,391.67] 0.31 MSH6 3.2% 0.4% 8.5 [1.63,55.30] 0.005* PMS2 0.6% 0.4% 1.66 [0.03,20.84] 0.52 PTEN 1.8% 0.1% 18.62 [3.03,196.06] 0.0004* TP53 0.4% 0.0% 7.5 [0.10,586.74] 0.22
Risk Factors for Congenital Syphilis Transmitted from Mother to Infant — Suzhou, China, 2011–2014
Authors: Yajie Wang, Minzhi Wu, Xiangdong Gong, Liang Zhao, Jing Zhao, Chuanwu Zhu, Chancong Gong
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Mother-to-child transmission of syphilis remains a major global public health issue, and elimination of congenital syphilis is one of the millennium development goals of the World Health Organization (1). In 2012, an estimated 930,000 maternal syphilis infections caused 350,000 adverse pregnancy outcomes, including 143,000 early fetal deaths and stillbirths, 62,000 neonatal deaths, 44,000 preterm or low-weight births, and 102,000 infected infants worldwide (2). In China, the number of congenital syphilis cases reported annually increased from 468 in 2000 to 10,032 in 2013; the corresponding national congenital syphilis incidence rate increased nearly 26-fold, from 2.6 cases per 100,000 live births in 2000 to 69.9 in 2013 (3,4). To examine risk factors for mother-to-child transmission of syphilis, a cohort of pregnant women with a new syphilis diagnosis and their live-born infants was recruited during July 2011-July 2014 in Suzhou, in eastern China. Multivariable logistic regression results demonstrated that gestational age >36 weeks at the time of maternal syphilis diagnosis, higher maternal titers of rapid plasma reagin (RPR) and higher Treponema pallidum particle agglutination assay (TPPA) titers are risk factors for congenital syphilis. Among women with syphilis diagnosed at >36 weeks' gestational age, three quarters were migrant women. Recommendations for strengthening community and provider education about mother-to-child transmission of syphilis, early diagnosis and timely treatment of syphilis in pregnancy, and improving and providing access to prenatal care and screening migrant pregnant women with temporary residence status might reduce the incidence of congenital syphilis in China.
Phase II study of apatinib: A novel VEGFR inhibitor in pretreated patients with metastatic penile cancer.
Authors: Sheng Zhang, Fei Liang
Journal: Journal of Clinical Oncology (2019)

TPS538 Background: Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2 and has been approved as monotherapy for treatment of metastatic gastric cancer in China. This phase II study aims to evaluate the efficacy and safety of apatinib monotherapy in pretreated patients with metastatic penile cancer in China (all patients have failed cisplatin-based chemotherapy previously). Methods: From October 2016 to May 2018, 9 patients were enrolled, and eight patients were eligible for efficacy analysis. All patients received apatinib 500 mg/day p.o. in a 4-week cycle, with the endpoint progression-free survival (PFS). This trial is ongoing. Longer follow-up and complete enrollment are needed for the final efficacy assessment. Clinical trial information: UMIN000021849.
Abstract P258: Novel Dual-task Balance Challenge to Prevent Falls in Older Adults With Cardiovascular Disease Risk Factors
Authors: Ruth E Taylor-Piliae, Chiu-Hsieh (Paul) Hsu, Nima Toosizadeh, Jane Mohler
Journal: Circulation (2019)

Background: Fall injuries are responsible for significant health care utilization, disability, loss of independence, and high costs among community-dwelling older adults with cardiovascular disease risk factors (CVD-RF). A Matter of Balance (MOB) is a national community-based fall prevention program, which focuses on cognitive restructuring to manage concerns about falling, but does not include a balance-training component. We hypothesize if MOB added to a dual-task balance challenge (DTBC) comprising weight transfer using fixed and random ordering of ankle reaching tasks, while simultaneously challenging attention—would lead to reduced fall risk. Objectives: To assess participants’ acceptance and satisfaction with the 4-week MOB and MOB plus DTBC interventions, safety and adherence, and examine changes in fall risk (balance, gait, and fear of falling) post-intervention. Methods: A single-blind, two-group, randomized pilot study, among community-dwelling older adults with CVD-RF at high fall risk. MOB classes were 2-hours, 2x/week for 4 weeks, with 15 minutes of social time. MOB+DTBC classes followed the same curriculum with 15 minutes of ankle reaching tasks while simultaneously challenging attention. Acceptability and satisfaction were obtained by self-report, study staff monitored safety and adherence during class. Balance and gait were objectively assessed using LEGSys™ (BioSensics, LLC), while the Falls Efficacy Scale International (FES-I) assessed fear of falling. We used t-tests for continuous variables and Fisher’s exact test for categorical variables. Results: At high fall risk older adults (n=16, mean age=74±8 years), mainly retired (95%, n=15), women (88%, n=14), with &gt;13 years education (81%, n=13), diabetes (25%, n=4), dyslipidemia (70%, n=12), and hypertension (63%, n=10) completed the study (drop-outs, n=1). Participants reported high levels intervention acceptability and satisfaction (mean score=9±1.3, 1=least, 10=most), no safety issues (0%), with very high adherence rates (&gt;94%), regardless of group assignment. Participants in the MOB group (n=7) had no significant within group changes in fall risk post-intervention (p&gt;0.05). Conversely, participants in the MOB plus DTBC group (n=9) had significant improvements in balance (eyes open test=ankle sway, p=0.02; eyes closed test=hip sway, p=0.03 and center of mass, p=0.01) and gait (fast pace=stride time, p=0.04 and double support, p=0.02), with less fear of falling (p=0.04) post-intervention, when compared to baseline. Conclusions: Reducing fall risk factors and preventing falls are essential for older adults with CVD-RF, to ensure that they continue to live safely and independently. The addition of DTBC to the nationally-used standard MOB curriculum may enhance both balance and cognitive function, and lead to reduced fall risk among community-dwelling older adults with CVD-RF.
Using Machine Learning to Identify Heterogeneous Effects in Randomized Clinical Trials—Moving Beyond the Forest Plot and Into the Forest
Authors: Benjamin A. Goldstein, Joseph Rigdon
Journal: JAMA Network Open (2019)

Joseph Scarpa, MD, PhD; Emilie Bruzelius, MPH; Patrick Doupe, PhD; Matthew Le, MS; James Faghmous, PhD; Aaron Baum, PhD
Is colorectal cancer screening missing the boat?
Authors: Zhobin Moghadamyeghaneh, Mark Hanna, Grace Hwang, Michael Phelan, Joseph Carmichael, Steven D Mills, Alessio Pigazzi, Jason A. Zell, Michael J. Stamos
Journal: Journal of Clinical Oncology (2015)

e14703 Background: Colorectal cancer (CRC) incidence is rising among patients under age 50. As such, we set out to determine the proportion of CRC-related hospital admissions and distribution of colon cancer by stage in different age groups. Methods: The NIS database for 2002-2012 was used to investigate trends of colorectal cancer hospitalization by age and the NSQIP database for 2012-2013 was used to investigate contemporary stage diagnosis for colon cancer in different age groups. Results: A total of 1,655,068 patients were admitted to the hospital with diagnosis of CRC. Although the number of hospitalized CRC patients decreased from 2002-2012, the decrease was predominantly in patients older than 65 years (P < 0.01) and in colon cancer compared to rectal cancer patients (P < 0.01). The percentage of patients younger than 65 years increased from 36% in 2002 to 44.8% in 2012, and the percentage of patients under age 50 increased from 8.8% to 10.8%. Patients with rectal cancer were significantly younger than patients with colon cancer (mean age = 65 vs. 69, P < 0.01). Overall, 50.4% of patients with rectal cancer were younger than 65 years and 13.9% were younger than 50, compared to 36% and 8.5% for colon cancer (P < 0.01for both ages). This younger than 50 group also had significantly higher rate of advanced disease (stage 3/4) compared to patients older than 50 (66% vs. 47%, P < 0.01). The most common stage in patients older than 50 was stage 2 (32.1%). However, the most common stage in patients younger than 50 was stage 3 (35.1%). Conclusions: There was a steady decrease in the number of hospitalized patients with colorectal cancer, primarily attributable to a decrease in the older age group during the last decade. However, the percentage of hospitalized cancer patients younger than 50 years is increasing. Patients younger than 50 have higher rates of advanced disease, compared to older patients. Future CRC screening recommendations should take these findings into consideration.
A phase III, randomized, open label, multicenter, global study of first-line (1L) durvalumab in combination with standard of care (SOC) chemotherapy and durvalumab in combination with tremelimumab and SOC chemotherapy versus SOC chemotherapy alone in patients with unresectable locally advanced or metastatic urothelial cancer (UC).
Authors: Matt D. Galsky, Andrea Necchi, Srikala S. Sridhar, Osamu Ogawa, Natasha Angra, Stephan Hois, Philip He, Dana C. Ghiorghiu, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2019)

TPS4590 Background: Despite high response rates to 1L SoC for locally advanced or metastatic UC chemotherapy (gemcitabine + cisplatin or gemcitabine + carboplatin for patients who are cisplatin-ineligible [poor performance status, impaired renal function, comorbidities]), most patients experience disease progression. Novel strategies such as combining chemotherapy and immunotherapy offer hope for improving clinical outcomes. Durvalumab is a selective, high affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80. Tremelimumab is a human IgG2 mAb directed against CTLA-4. The mechanisms of action of PD-1 and CTLA-4 are nonredundant, so targeting both checkpoint pathways may have additive or synergistic efficacy compared with monotherapy. Studies of platinum-based chemotherapy combined with checkpoint blockade in other tumor types have yielded improved efficacy with acceptable safety and support exploration of this approach for 1L locally advanced or metastatic UC. Methods: NILE (NCT03682068) is a randomized, open-label, multicenter, global trial that will enroll approximately 1265 patients with histologically or cytologically documented, unresectable, locally advanced, or metastatic transitional cell carcinoma of the urothelium. Patients will be randomized (1:1:1) to durvalumab + SoC chemotherapy, durvalumab + tremelimumab + SoC chemotherapy, or SoC chemotherapy as 1L therapy. Primary endpoints are progression-free survival using blinded independent central review assessments per RECIST 1.1 and overall survival (OS). Secondary endpoints include objective response rate, OS at 24 months, proportion of patients alive and progression free at 12 months, duration of response, disease control rate, time from randomization to second progression, and health-related quality of life. Safety, pharmacokinetics, immunogenicity, and biomarkers will also be assessed. The study opened for enrollment in September 2018. 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 Genitourinary Cancers Symposium. Clinical trial information: NCT03682068.
Abstract P375: Using a Recalibrated Cardiovascular Disease Risk Score is Not Adequate to Predict Risk of Recurrence Within 3 Years in Australian Survivors of Stroke
Authors: David Ung, Richard P Gerraty, Judith Frayne, Muideen T Olaiya, Joosup Kim, Velandai K Srikanth, Thanh Phan, Dominique A Cadilhac, Mark R Nelson, Christopher F Bladin, Amanda G Thrift
Journal: Circulation (2019)

Background: Prognostic performances of models predicting risk of recurrent events of cardiovascular disease (CVD) are not adequate for use in clinical settings. We aimed to determine whether adapting the Framingham Risk Score (FRS) to an Australian population could effectively predict recurrent cardiovascular outcomes. Methods: Patients comprised survivors of stroke/TIA who participated in the Shared Team Approach between Nurses and Doctors For Improved Risk factor Management (STAND FIRM) trial (n = 563). We used standardised anthropometric, biochemical and blood pressure data, collected at baseline, to evaluate risk factors for stroke/TIA. Cox proportional hazards regression models were used to determine the risk of recurrence of CVD-related events and deaths within 3 years after stroke/TIA; adjudicated by two independent stroke specialists. Regression estimates were then used to recalibrate the coefficients used by the FRS, and performance of the model assessed. Results: In women, the recalibrated FRS model had poor discrimination (C-statistic = 0.634) and appeared to better predict CVD recurrence (AUC = 0.664) than the original FRS model (AUC = 0.598). However in men, the recalibrated FRS model had poor discrimination (C-statistic = 0.604) and prediction of CVD recurrence (AUC = 0.632) similar to the original FRS model (AUC = 0.606). Conclusion: The original FRS and recalibrated FRS models appeared to perform poorly in Australian men and women with stroke. The identification of relevant risk factors, easily measured in a clinical setting, may help clinicians better monitor the risks of their patients and enhance secondary prevention strategies.
Doctors’ access to rest facilities included in GMC annual training surveys
Authors: Harriet Pike
Journal: BMJ (2019)

For the first time doctors will be asked about their access to rest facilities and study spaces by the General Medical Council in its annual training surveys.

The regulator, responsible for overseeing medical education and training across the UK, has added questions about workplace rest and catering facilities, transport home after shifts, access to wifi, and the quality of online library and learning resources in …
Enhanced mammalian genome editing by new Cas12a orthologs with optimized crRNA scaffolds
Authors: Fei Teng, Jing Li, Tongtong Cui, Kai Xu, Lu Guo, Qingqin Gao, Guihai Feng, Chuanyuan Chen, Dali Han, Qi Zhou, Wei Li
Journal: Genome biology (2019)

CRISPR-Cas12a/Cpf1, a single RNA-guided endonuclease system, provides a promising tool for genome engineering. However, only three Cas12a orthologs have been employed for mammalian genome editing, and the editing efficiency as well as targeting coverage still requires improvements. Here, we harness six novel Cas12a orthologs for genome editing in human and mouse cells, some of which utilize simple protospacer adjacent motifs (PAMs) that remarkably increase the targeting range in the genomes. Moreover, we identify optimized CRISPR RNA (crRNA) scaffolds that can increase the genome editing efficiency of Cas12a.
TITAN: Phase III study of doxorubicin/cyclophosphamide (AC) followed by ixabepilone (Ixa) or paclitaxel (Pac) in early-stage, triple-negative breast cancer (TNBC).
Authors: Denise A. Yardley, Linda D. Bosserman, Mark Robert Keaton, Mary Audrey Ackerman, Sharon A. Goble, Dianna Shipley, Emile Salloum, William N. Harwin, Brooke R. Daniel, John D. Hainsworth, Howard A. Burris
Journal: Journal of Clinical Oncology (2015)

1000 Background: Ixa is a microtubule stabilizer able to target mechanisms conferring taxane resistance including high b tubulin III expression, seen in TNBC. Here, we present preliminary results of a phase III study of AC followed by Ixa or Pac in patients (pts) with early stage TNBC. Methods: Patients with resected TNBC (ER and PR < 10% by local IHC, HER2 IHC 0-1+ or FISH/CISH negative) and no evidence of metastatic disease were eligible. Pts were randomized 1:1 to AC (60/600mg/m2) q3wks x4 followed by either Ixa (40mg/m2 q 3wks x4) (AC/Ixa) or weekly Pac (80mg/m2x12 weeks) (AC/Pac). Growth factor use was allowed per MD discretion. Following phase II neoadjuvant results that demonstrated no AC/Ixa efficacy advantage compared to AC/Pac (including in tumors with high b III tubulin levels), the sample size of this study was revised to 590 patients to detect a 30% reduction in risk of recurrence with AC/Ixa. Results: Between December 2008 and March 2011, 614 pts (median age 54, 18% African American, 32% lymph node positive, 50% T2) were randomized (AC/Ixa, 306; AC/Pac, 308). 84% AC/Ixa and 77% AC/Pac pts completed protocol treatment (tx). 23 (8%) Ixa pts and 47 (16%) Pac pts discontinued tx due to toxicity. Dose reductions/dose delays occurred in 78 (26%)/121 (39%) Ixa pts and in 99 (33%)/158 (52%) Pac pts. Neuropathy was the major reason for dose reduction and tx discontinuation. G3/4 neutropenia rates were low at 11% with Ixa vs 6% with Pac, accompanied by fever in only 4 patients. At a median follow up of 46 mo, 75 pts have relapsed (AC/Ixa, 37; AC/Pac, 38). Median time from initial diagnosis to relapse was 20.8 mo. The 3 year disease-free survival of the Ixa arm was 88% (95% CI: 0.84, 0.91) and 89% (95% CI:0.85, 0.92) for the Pac arm. The hazard ratio (Ixa arm vs Pac arm) was 0.99 (95% CI: 0.63, 1.56, p = 0.98). 51 pts (AC/Ixa, 28; AC/Pac, 23) have died, 42 due to disease. Conclusions: AC with Ixa or Pac performed well in this early stage TNBC population with no difference in efficacy evident. Pts receiving AC/Pac had higher rates of neuropathy and more dose modifications. Clinical trial information: NCT00789581.