tbuckley/cabot-search huggingface dataset:
Abstract P479: Feasibility Study to Compare Heart Failure Risk Prediction Tools in the Emergency Department
Authors: Andrew Scott, Kevin Chronowski, Snigdha Peddireddy, Sarah Fatima, Bailey DeBarmore, Patricia Chang, Mirnela Byku, Timothy F Platts-Mills, Eugenia Quackenbush, Michele Jonsson-Funk, Michelle L Meyer
Journal: Circulation (2020)

Background: In United States (US) emergency departments (ED), ~80% of patients presenting with exacerbation of heart failure (HF) symptoms are admitted to the hospital. However, some patients are at low-risk of adverse outcomes and might be effectively managed as outpatients. While ED HF risk prediction tools guide admission or discharge decisions, they have not been compared, are not routinely used in EDs, and do not include patient-reported outcomes that may be associated with prognosis. Objective: To assess the feasibility of collecting variables for three published ED-based HF risk prediction tools (table) and the capacity to collect participant-reported outcomes. Methods: We screened a convenience sample of patients age ≥20 years with symptoms of HF (e.g. shortness of breath, edema) receiving care in a US ED. We collected information from medical records, and administered a questionnaire to collect patient-reported outcomes and a 3-minute walking test. We developed a safety protocol to identify participants ineligible for the walking test. Results: We screened 66 patients and consented 31 (47%) participants. The average age was 61 years, 6 (19.4%) were female and 28 (90.3%) were admitted. We completed all the questionnaires with an average time of 31 minutes. For the walking test, 15 were ineligible per the safety protocol, 6 completed the test, and 10 did not consent. For the three HF tools, we collected an average of 93.4% of the variables needed per participant (range across tools 91.4%-97.7%; Table). The main missing variables were BMI on ED arrival (n=23) and troponin (due to hemolyzed values, n=5). Conclusion: We obtained complete data for the participant questionnaires, yet there were missing values for variables needed for the HF tools. The Emergency Heart Failure Mortality Risk Grade tool had the most complete data. If a research or clinical study plans to use these tools, the study protocol should include BMI and troponin measurements and consider alternative strategies to collect data, such as by self-report.
Weekly paclitaxel, cisplatin, and 24-hour infusion of high-dose 5-fluorouracil plus leucovorin (weekly TP-HDFL) in patients with metastatic or recurrent esophageal cancer
Authors: T. Huang, Y. Tsai, C. Lin, A. Cheng, K. Yeh, C. Hsu
Journal: Journal of Clinical Oncology (2007)

15165 Background: Paclitaxel (T), cisplatin (P), and 5-fluorouracil (5-FU) are active chemotherapy drugs for esophageal cancer. The 3-drug combination using a conventional 3-weekly schedule was active in patients with advanced esophageal cancer with response rate of 46% (Ilson DH et al: J Clin Oncol 1998;16:1826). The toxicity was substantial, with 57% grade 3/4 hematologic toxicities and 18% grade 3/4 peripheral neuropathy. We reported a multifractionated schedule using twice-weekly TP and weekly 5-FU (Lin CC et al: Anticancer Drugs 2007;18: in press). The multifractionated schedule, while induced comparable antitumor activity, had similar hematologic toxicities, less neuropathy, but more diarrhea than conventional 3-weekly schedule. The optimal way of combining T, P, and 5-FU remains to be defined. Methods: Patients with metastatic or recurrent esophageal cancer treated with weekly T, P, high-dose 5-FU plus leucovorin (weekly TP- HDFL) were retrospectively analyzed. The regimen consisted of T 70–80 mg/m 2 IV 1h D1, P 35 mg/m 2 IV 3h D2, 5-FU 2000 mg/m 2 plus leucovorin 300 mg/m 2 IV 24h D2, for 2 or 3 weeks followed by 1 week off. Results: Between Dec 2004 and Sep 2006, a total of 15 patients (male 14, squamous cell carcinoma 12) with a median age of 54 (range 37–76) were included. Eleven patients had de novo metastatic disease and 4 had recurrent disease. The disease extent included local esophageal tumor, lymph nodes, lung, liver, and bone in 13, 13, 5, 4, and 5 patients, respectively. The patients received an average of 3 cycles (range 1–5). Grade 3/4 neutropenia, leukopenia, thrombocytopenia, and infection occurred in 4, 3, 1, and 5 patients, respectively. No grade 3/4 vomiting, mucositis, diarrhea, and peripheral neuropathy occurred. The overall response rate was 33% (95% CI 12–87) (PR 5, SD 6, PD 4). With a median follow-up of 5 months, the median progression-free and overall survival were 3 (range 2–7) and 12.5 months (range 3+-12.5), respectively. Conclusions: Weekly TP-HDFL has a comparable activity and a better toxicity profile in patients with advanced esophageal cancer compared to previously reported 3-weekly or multifractionated schedule. (The study was supported by the grant of DOH95-TD-B-111- 001) No significant financial relationships to disclose.
Targeted chemoradiation for metastatic colorectal cancer: A phase I trial of oral capecitabine combined with <sup>131</sup>I- huA33
Authors: R. A. Herbertson, N. Tebbutt, S. Gill, F. T. Lee, B. Chappell, T. Cavicchiolo, E. Skrinos, A. Poon, T. Saunder, A. M. Scott
Journal: Journal of Clinical Oncology (2007)

4078 Background: HuA33 is a humanized antibody that targets the A33 antigen, which is highly expressed in intestinal epithelium and &gt;95% of human colon cancers, but not other normal tissues. Previous studies have shown huA33 can target and be retained in a metastatic tumor for 6 weeks, but eliminated from normal colonocytes within days. This phase 1 study used radio-labeled huA33 in combination with capecitabine chemotherapy to target chemoradiation to metastatic colorectal cancer. Methods: The primary objective was safety and tolerability of the combination of capecitabine and 131 I-huA33. Pharmacokinetics, biodistribution, immunogenicity, and tumor response were also assessed. Eligibility included measurable metastatic colorectal cancer, adequate hematological and biochemical function, and informed consent. An outpatient scout 131 I-huA33 dose was followed by a single therapy infusion one week later, when capecitabine was commenced. Dose escalation occurred over 5 dose levels. Patients were evaluated weekly, with tumor response assessment at the end of the12 week trial. Tumor targeting was assessed using gamma camera and single photon emission computerized tomography (SPECT) imaging. Results: 16 patients have enrolled with 2 currently on treatment, including one in the final dose cohort. Accrual will be completed by March 2007. The dose escalation protocol was amended following 2 dose limiting toxicities in the second cohort, but subsequent cohorts demonstrated good tolerability. Biodistribution analysis demonstrated excellent tumor targeting of the known tumor sites, expected transient bowel uptake, but no other normal tissue uptake. Maximal duration of stable disease is currently 3 years. Conclusions: 131 I-huA33 achieves specific targeting of radiotherapy to sites of metastasis and can be safely combined with chemotherapy. This provides an opportunity to deliver chemoradiation specifically to metastatic disease in colorectal cancer patients. [Table: see text] No significant financial relationships to disclose.
Creation of a Case-Finding Definition for Identifying Patients With Acute Pouchitis in Administrative Claims Data
Authors: Edward L. Barnes, Bharati Kochar, Hans H. Herfarth, Rachel W. Winter, Millie D. Long, Joshua R. Korzenik, Silvia F. Quevedo, Joseph A. Galanko, Mark Koruda, Michael D. Kappelman, Robert S. Sandler
Journal: Clinical Gastroenterology and Hepatology (2020)
Ten years of clinical trial data cannot legally be hidden from the public, US court rules
Authors: Owen Dyer
Journal: BMJ (2020)

US public health watchdogs have been failing for years in their legal duty to inform the public about the results of clinical trials, a federal court has found.

The US district court for southern New York ruled that an exemption granted by the Food and Drug Administration (FDA) and the National Institutes of Health (NIH) that allowed hundreds of studies to escape reporting requirements laid down by Congress was unlawful.1

Transparency advocates hailed the ruling but expressed concern that its impact could be limited, as the court said it lacked the power to compel the FDA and NIH to enforce existing laws on disclosure of trial results, which to date they have been reluctant to do.

Legislation passed in 1997 required the government to set up the website ClinicalTrials.gov, to promulgate results from clinical trials of products approved to treat serious diseases. But with no …
Doctors suspended after trans patient has vagina removed without consent
Authors: Clare Dyer
Journal: BMJ (2020)

Two urologists have been suspended from the UK medical register, one for mistakenly removing the vagina of a sex change patient who did not want it removed, and the other for altering the patient’s consent form to add a vaginectomy retrospectively.

Giulio Garaffa, a consultant urological surgeon with a special interest in andrology and reconstructive surgery and honorary senior lecturer at University College London Hospitals, was suspended for five months for carrying out the surgery in error on a patient transforming into a man.

Metoidioplasty, the surgical construction of a penis, is normally accompanied by vaginectomy. But in this case the patient had repeatedly said they did not want their vagina removed, and this was clearly marked in the notes, although …
Tyrosine kinases as possible therapeutic targets in pulmonary artery intimal sarcoma
Authors: B. Dewaele, G. Floris, R. Sciot, H. Prenen, A. Wozniak, L. Guillou, J. Coindre, C. Fletcher, P. Schöffski, M. Debiec-Rychter
Journal: Journal of Clinical Oncology (2007)

10055 Background: Pulmonary artery intimal sarcomas (PAIS) are very rare, highly malignant and clinically aggressive tumors, with yet elusive underlying pathogenic mechanisms and histogenesis. Our aim was to gain molecular insight in the oncogenic events leading to PAIS development, and to investigate the possibility of a pharmacological approach for the treatment of PAIS, specifically targeting the receptor tyrosine kinases (RTK) activated in these tumors. Methods: Fourteen cases of advanced high grade poorly differentiated PAIS were analyzed by immunohistochemistry and selectively by a variety of cytogenetic/molecular techniques, e.g. karyotyping, FISH, mRNA in situ hybridization, array-CGH, tyrosine kinases RT-PCR assay and Western blotting analysis. The study was supplemented by sequencing of PDGFRA, PDGFRB, KIT, VEGFR-1, VEGFR-2 and EGFR genes. Ex vivo functional assays were applied to test the sensitivity of PAIS primary tumor cells to different, clinically approved RTK inhibitors. Results: We demonstrate that (1) PAIS do not have mutations within the kinase domains of PDGFRs, KIT, VEGFRs or EGFR, (2) all cases show a similar cytogenetic molecular profile, characterized by amplification of PDGFRA/KIT/VEGFR2 and MDM2/CDK4 genes, while EGFR, PDGFRB and VEGFR1 are frequently polysomic but rarely highly amplified, (3) high level of expression of PDGFRA, VEGFR1/VEGFR2 and EGFR is uniformly present in the tested tumors, (4) PAIS demonstrate activation (phosphorylation) of PDGFRA and downstream PI3K-AKT and MAP-Kinase signaling pathways, (4) in ex vivo assays, a potent effect of BMS354825 on proliferation and survival of primary cells of PAIS is proven. Conclusions: PDGFRA is amplified and activated in PAIS, thus constituting one of many possible targets for the therapy. Tested inhibitors showed differential efficacy for inhibition of PAIS cells by ex vivo assays. No significant financial relationships to disclose.
Abstract P105: Associations of Childhood Obesity With Cardiometabolic Risk Factors by Era of Birth: The I3c Consortium
Authors: Jessica G Woo, Lydia A Bazzano, Trudy L Burns, Stephen R Daniels, Terence Dwyer, Tian Hu, David R Jacobs, Markus Juonala, Ronald J Prineas, Olli T Raitakari, Alan R Sinaiko, Julia Steinberger, Alison Venn, Elaine M Urbina
Journal: Circulation (2020)

Introduction: The prevalence of childhood obesity has increased dramatically over the past several decades, but it is unclear whether children and adolescents with obesity are experiencing more or fewer cardiometabolic risks from obesity now compared with several decades ago. This study leverages data from over 2600 children and adolescents with obesity born from 1951-1996 to determine whether relationships of obesity with cardiometabolic risk have changed over time. Methods: The first study visit, age 3-19, was used to classify individuals by era of birth (quartiles: 1951-1963, 1964-1969, 1970-1974, 1975-1996), weight status (obesity defined as BMI&gt;CDC 95 th %ile and &lt;120% of the 95 th %ile), high BP (SBP or DBP&gt;95 th %ile), high total cholesterol (TC&gt;170 mg/dl), high LDL-C (&gt;110 mg/dl), high triglycerides (TG&gt;100 mg/dl), high glucose (&gt;100 mg/dl), and low HDL-C (&lt;40 mg/dl males, &lt;50 mg/dl females). Participants with obesity (excluding severe obesity) were included in this analysis. Logistic regressions were adjusted for age, sex, race and study cohort to calculate odds ratios relative to the most recent era of birth (1975-1996). Results: The prevalence of childhood obesity increased from 6.1% in the earliest birth era to 7.7% in the most recent (p&lt;0.0001). The adjusted odds of children with obesity having high TC (p&lt;0.0001), high TG (p&lt;0.0001), and high BP (p=0.003) were half as likely among children born between 1964-69 or 1970-74, compared with the most recent birth era (Table). The odds of children with obesity having high LDL (p=0.59), low HDL (p=0.17) or high glucose (0.33) did not differ across birth eras. Conclusions: Childhood obesity in more recent decades has not only become more prevalent, but is associated with greater risks of high TC, high TG and high BP. However, the risks of high LDL, low HDL and high glucose have not significantly changed among children with obesity who were born between 1951 and 1996. Thus, comparisons of children or adolescents with obesity across eras should consider these differing risk profiles.
Abstract MP24: Does Sleep Disturbance Vary Between Current Combustible and Electronic Cigarette Users?
Authors: Freda Patterson, Benjamin Brewer, Michael A Grandner
Journal: Circulation (2020)

Smoking cessation is critical to the goal of reducing cardiovascular diseases. Combustible cigarette smokers are more likely to have poor sleep health that is exacerbated upon cessation and can cause relapse. Use of electronic cigarettes has increased exponentially since their introduction to the market in 2007. Not known is the extent to which sleep disturbances that is common in combustible cigarette smokers is also associated with e-cigarette use. Using data collected as part of the Behavioral Risk Factor Surveillance System (BRFSS), we examined the association between non-smoking, smoking combustible, electronic, and dual (combustible + electronic) cigarettes with sleep disturbances (short sleep duration, daytime sleepiness, insomnia symptoms). Exact matching was used to generate matched samples of non-smokers (n=472), combustible only (n=472), e-cigarette only (n=472), and dual use (n=472) smokers on the variables of age, sex, race, educational attainment, overweight/obese, and days of poor mental health in the last month. In a univariate linear regression model of insomnia symptoms, when compared to non-smokers, cigarette only smokers reported an average of 0.87 (p=0.038) more days of insomnia symptoms in the last month while dual users reported an average of 0.77 (p=0.063) more (Table 1). For daytime sleepiness, dual users reported an average of 0.85 (p=0.002) more days with daytime sleepiness in the last month as compared to non-smokers. In terms of sleep duration, when compared to non-smokers, cigarette smokers reported getting 0.28 (p=.021) fewer hours of sleep, and dual users reported getting 0.34 fewer hours of sleep (p=0.005). Overall, as compared to non-smokers, combustible and dual cigarette smokers in this sample reported more disturbed sleep. Dual use smokers may be particularly vulnerable to sleep deficits, that in turn, may impede efforts to quit smoking and improve cardiovascular health.
Your athlete-patient has a high coronary artery calcification score—‘Heart of Stone’. What should you advise? Is exercise safe?
Authors: Katharina Lechner, Bianca Spanier, Benjamin Lechner, Johannes Scherr
Journal: British Journal of Sports Medicine (2020)

Coronary artery calcification (CAC) is a strong marker of subclinical coronary atherosclerosis and leading authorities recommend CAC scoring to help inform patient management decisions in cardiovascular disease (CVD) prevention.1 2 This will result in an increasing number of athlete-patients with subclinical coronary atherosclerosis presenting to sport and exercise medicine physicians, raising questions about exercise recommendations in this subgroup. With a specific focus on the recent outcomes data of DeFina and colleagues3 we extend our recent discussion of the topic2 by focusing on how to manage athlete-patients with elevated CAC in the sport and exercise medicine setting.

A breakthrough in reporting the association of CAC and mortality risk across different activity levels came from a recent study of 21 758 healthy male participants without prevalent CVD. Higher levels of leisure-time physical activity were associated with a lower risk of mortality at any given level of CAC.3 The authors reported a higher risk metabolic profile (ie, higher baseline blood pressure, higher glucose concentrations and higher triglycerides) in the high volume exercise group with elevated CAC ≥100 AU …
Interplay between whole-genome doubling and the accumulation of deleterious alterations in cancer evolution
Authors: Saioa López, Emilia L. Lim, Stuart Horswell, Kerstin Haase, Ariana Huebner, Michelle Dietzen, Thanos P. Mourikis, Thomas B. K. Watkins, Andrew Rowan, Sally M. Dewhurst, Nicolai J. Birkbak, Gareth A. Wilson, Peter Van Loo, Mariam Jamal-Hanjani, Charles Swanton, Nicholas McGranahan
Journal: Nature Genetics (2020)
Doctors didn’t breach duty of care by not telling woman her father had Huntington’s disease
Authors: Clare Dyer
Journal: BMJ (2020)

A woman who sued three NHS trusts for negligence for not telling her while she was pregnant that her father had Huntington’s disease has lost her case in the High Court.1

The woman, referred to as ABC, claimed that she would have undergone a termination had doctors caring for her father, anonymised as XX, told her that he had the disease and that she had a 50% chance of inheriting the gene.

But Mrs Justice Yip ruled that two of the trusts involved in her father’s care had no duty of care to her, a third party. While South West London and St George’s Mental Health NHS Trust, where she was participating in family therapy, had a duty of care, doctors there had not breached the duty, the judge …
Impact of chemoradiotherapy for locally advanced head and neck cancer on swallowing function
Authors: E. Burke, L. Goguen, R. Tishler, L. Wirth, M. Posner, E. Hempel, A. Allen, R. Costello, R. Haddad
Journal: Journal of Clinical Oncology (2007)

6054 Background: We examined the impact of chemoradiotherapy (CRT) on swallowing function in a group of patients treated for locally advanced head and neck cancer in an ongoing randomized phase II study with concurrent CRT, with or without Ethyol. Methods: Chemotherapy consisted of weekly carboplatin AUC 1.5 and paclitaxel at 45 /m 2 for 4 weeks. Radiation was delivered using a 3 field technique with a concomitant boost schedule to a total dose of 72 Gy. Patients were randomized to receive or not receive daily subcutaneous Ethyol. Patients had video swallow studies at the start of radiation and 8, 12, 24 and 52 weeks post chemoradiotherapy. Dysphagia and weight loss were monitored. Video swallow study reports were collected and the incidence of penetration, aspiration, pharyngeal residue and upper esophageal narrowing analyzed. Results: Baseline data were available for 31 patients out of 43 enrolled. 29% of the patients penetrated, 6.4% aspirated and 29% had pharyngeal residue. Patients on both arms of the study had a steady decline in swallowing function from onset until 24 weeks post radiation. Penetration, aspiration and pharyngeal residue were consistently noted at all time points and improvements in deglutition were seen on the 52-week post radiation video swallow. Forty percent of the patients (17/43) had narrowing in the upper esophagus. On average, a third of the patients examined required dilations. The remaining patients with esophageal narrowing were able to advance their diet and have their feeding tubes removed without dilations. The average time from the end of the treatment to PEG removal was 219 days. Conclusion: Based on the video swallow studies that were conducted, patients had a gradual decline in swallowing function from initiation of CRT until 24 weeks post. Esophageal narrowing was common, often requiring dilation. Given that it takes 7 months on average for the feeding tubes to come out, we recommend that these patients undergo intensive swallowing therapy and continuous long term follow up and assessment at two and possibly three years post CRT. Study is ongoing. No significant financial relationships to disclose.