tbuckley/cabot-search huggingface dataset:
Abstract 12: Outcomes After Pediatric Extracorporeal Cardiopulmonary Resuscitation: Do Quantitative CPR Metrics Matter?
Authors: Tia T Raymond, Ivie Esangbedo, Priscilla Yu, Todd Sweberg, Javier J Lasa, Dana E Niles, Xuemei Zhang, Heather Griffis, Richard Hanna, Vinay M Nadkarni
Journal: Circulation (2019)

Introduction: Duration of conventional cardiopulmonary resuscitation (CPR) prior to ECMO cannulation (ECPR) has been shown to be associated with worse survival outcomes, yet conflicting reports exist. Hypothesis: ECPR patients who receive guideline-compliant CPR will have improved survival to hospital discharge (SHD) compared to patients who do not receive guideline-compliant CPR, regardless of CPR duration. Methods: Prospective cohort from PediRES-Q sites of IHCA in children ≤ 18 yo requiring ECMO to achieve ROSC. We assessed compliance of 60-sec chest compression (CC) epochs via metric data (Zoll R-series, Chelmsford, MA) with 2015 AHA guideline targets. Guideline-compliant CPR was defined as an IHCA with &gt;60% epochs meeting compliance criteria for metric data. Differences were assessed utilizing Wilcoxon rank-sum and Chi-square tests. Logistic regression assessed the association between compliance and SHD, adjusting for age, arterial line, and duration of CPR. Results: From 10/2015 to 3/2019, 62 index ECPR events (&gt; 5 epochs) in 20 infants (&lt;1 yo), 24 children (1-&lt;8 yo), and 18 adolescents (8-≤18 yo) with CPR quality metric data were utilized from 15 sites. Median CPR duration 52 mins (IQR 45,70), median weight 11.6 kgs (IQR 6.8,29.8), and 38/62 patients (61%) had a cardiac diagnosis. Guideline compliance was not associated with SHD. Adjusting for age, presence of arterial line, and duration of CPR, guideline compliance was not significantly associated with SHD. However, age and duration of CPR were significantly associated to SHD, as 8-&lt;18 yo had 85% lower odds of SHD than &lt; 1 yo (aOR=0.15 {0.03, 0.73}; P=0.019) and every minute increase in duration of CPR decreased odds of survival by 4% (aOR=0.96 {0.94,0.99}; P=0.009). Conclusion: No SHD benefits were found among ECPR patients who received guideline-compliant CPR compared to patients who do not. Older patients and those with longer CPR duration had worse SHD outcomes irrespective of guideline-compliant CPR.
Significance of <i>ERCC1</i> and <i>HER2</i> expression in human colon carcinomas
Authors: A. V. Kaskara, A. G. Antonacopoulou, C. D. Scopa, A. G. Rigopoulos, G. Iconomou, V. Georgoulias, H. Kalofonos
Journal: Journal of Clinical Oncology (2007)

14534 Background: Predictive and prognostic markers need to be established in colon cancer in order to tailor chemotherapy and, therefore, improve efficacy of adjuvant treatment. In this study, expression of the excision repair cross-complementing 1 (ERCC1) and HER2 tyrosine kinase receptor genes was evaluated in human colon carcinomas. Moreover, expression levels were associated with survival, time to disease progression and various clinicopathologic parameters. Methods: Fifty formalin fixed paraffin embedded tissues of primary colon carcinomas, resected from an equal number of patients at the University Hospital of Patras, Greece were studied. Forty four patients were treated with adjuvant chemotherapy and four patients with chemotherapy for advanced disease. Total RNA was extracted from tissues, quantified and reverse transcribed. Levels of ERCC1 and HER2 mRNA were quantified using Taqman probes in real time PCR and expressed relative to a calibrator. Results: ERCC1 and HER2 mRNA were detected in 92% and 82% of cases respectively, although overexpression was observed in 43.5% and 26.8%. Levels of expression were not related to age, stage, grade and overall survival. There was a significant association between overexpression of ERCC1 and time to disease progression (p&lt;0.05) although this was not observed for HER2. There was a trend towards decreased relapse following adjuvant therapy in patients with low expression levels of ERCC1 and HER2 mRNA levels. However this difference failed to reach significance. Expression levels of ERCC1 and HER2 were not correlated with each other. Furthermore, coexpression of the two molecules was not related to time to disease progression. Additionally, 99.5% and 93.7% of patients with low expression of ERCC1 and HER2, respectively, having received adjuvant therapy were alive at the 36 months follow up. Conclusions: These data suggest that overexpression of ERCC1 is significantly associated with time to disease progression in colon cancer. Further studies of ERCC1 as a prognostic or predictive marker are warranted. No significant financial relationships to disclose.
Abstract P367: Peripheral Artery Disease and Subsequent Risk of Hospitalized Infectious Disease in Older Individuals: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Yejin Mok, Junichi Ishigami, Pamela L Lutsey, Hirofumi Tanaka, Michelle Meyer, Gerardo M HEISS, Kunihiro Matsushita
Journal: Circulation (2020)

Background: Patients with cardiac disease and stroke have a high risk of infection, and several prevention programs target those patients. However, data among patients with peripheral artery disease (PAD) are lacking. Methods: In 5,055 ARIC study participants without a preceding infection within three months of visit 5 (age 71-90 years in 2011-2013), we assessed whether PAD (clinical history or ankle-brachial index [ABI] ≤0.90) was associated with subsequent hospitalization for infections. We ascertained infections using ICD-9 codes at discharge to identify overall infection as well as its major subtypes (i.e., cellulitis, bloodstream infection, pneumonia, and urinary tract infection). We also stratified participants with PAD by history of concomitant coronary heart disease (CHD) or stroke. Multivariable Cox regression models were used to estimate adjusted hazard ratio (aHR). Results: During the median follow-up of 5.4 years, 1103 (44.4 rate per 1000 person-years) had hospitalizations with infection. As compared to those with an ABI of 1.11-1.20, participants with PAD were at greater risk of overall infection (aHR 1.67 [95% CI 1.38, 2.02], as were those with borderline low ABI (0.91-1.00) (aHR 1.89 [1.54, 2.31]). Consistent results were observed when the major subtypes of infection were explored. When we compared four groups according to PAD and CHD/stroke, PAD alone had a higher risk of infection similar to those with PAD plus CHD/stroke compared to those without PAD or CHD/stroke (Figure). Of note, PAD alone showed the highest risk of bloodstream and urinary tract infections. Conclusions: PAD and borderline low ABI were independently associated with greater risk of hospitalized infection among older adults. The contribution of PAD to elevated infection risk appeared even larger than that of CHD/stroke. Our study suggests that PAD patients should be considered for preventive strategies for infection (e.g., vaccination).
Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults
Authors: Lucia Seminario-Vidal, Daniela Kroshinsky, Stephen J. Malachowski, James Sun, Alina Markova, Thomas M. Beachkofsky, Benjamin H. Kaffenberger, Elizabeth N. Ergen, Melissa Mauskar, Alina Bridges, Cody Calhoun, Adela R. Cardones, Steven T. Chen, James Chodosh, Jonathan Cotliar, Mark D.P. Davis, Katherine L. DeNiro, Arturo R. Dominguez, Juliana Eljure-Téllez, Alisa Femia, Lindy P. Fox, Anisha Guda, Caroline Mitchell, Arash Mostaghimi, Alex G. Ortega-Loayza, Cindy Owen, Helena Pasieka, Sahand Rahnama-Moghadam, Hajirah N. Saeed, Rebecca B. Saunderson, Swapna Shanbhag, Victoria R. Sharon, Lindsay Strowd, Samantha Venkatesh, Karolyn A. Wanat, David A. Wetter, Scott Worswick, Robert G. Micheletti
Journal: Journal of the American Academy of Dermatology (2020)
Developing your career as a neurosurgeon
Authors: Jacqui Wise
Journal: BMJ (2020)

Life as a neurosurgeon is varied, challenging, and rewarding. There are opportunities to subspecialise in a variety of areas or to combine your work with academic research or a non-clinical role.

A certificate of completion of training is awarded by the General Medical Council once the required training has been successfully completed and the trainee is deemed competent by the specialist advisory committee. They will then be placed on the specialist register and allowed to apply for consultant posts.

Newly appointed NHS consultants must be competent to manage unselected emergency and urgent admissions to a regional neurosurgical unit. They will be capable of taking full responsibility for the continuing care of patients in a neurosurgical unit. Importantly, they will be proficient in all aspects of the clinical and emergency operative management of patients presenting with the essential neurosurgical conditions. A consultant neurosurgeon will also have demonstrated the potential to lead a clinical team.

Neurosurgical services are usually provided in tertiary regional neuroscience centres situated in major cities serving populations of between 1 million and 3.5 million. There are 40 neurosurgical units in the UK and Ireland.1

Competition for consultant posts is fierce and, in order to increase their employability, …
An observational study of metastatic renal cell carcinoma patients prior to initiation of initial systemic therapy.
Authors: Elizabeth R. Plimack, Cheryl Nemec, Paul Elson, Cristina Suarez, Tanya B Dorff, James M. G. Larkin, Cecilia McAleer, Isaac Nuñez, Rosalie Anne Fisher, Brian I. Rini
Journal: Journal of Clinical Oncology (2012)

TPS4679 Background: The biology of metastatic RCC is extremely diverse, including a subpopulation of patients with indolent growth of metastases. Because of the acute and chronic toxicity and assumed non-curative nature of current systemic targeted therapy, a select subset of patients may be better served with initial surveillance. Such an approach may allow for deferral of systemic therapy to minimize overall treatment-related toxicity burden while maintaining treatment benefit. Methods: A prospective phase II trial is being conducted to characterize the clinical course of patients with mRCC who defer initial systemic treatment. Appropriate patients are selected by the treating physician based on an observed indolent growth pattern. As such, there is a 12 month window allowed between the first diagnosis of metastatic disease and study entry. Patients must be treatment-naïve, asymptomatic, with histologically confirmed mRCC and clinically-evident, measurable disease to be eligible. Radiographic assessment is performed at baseline, every 3 months for year 1, every 4 months for year 2, then every 6 months. The primary objective is to characterize the clinical outcome of patients on observation in terms of time to RECIST defined disease progression and time to initiation of systemic treatment. Secondary endpoints include measurement of disease-related symptoms and depression/anxiety using standardized questionnaires (FKSI-DRS and HADS), as well as correlative endpoints analyzing the immune response over time for which blood is being collected for immune assays (TH1/TH2 phenotype, Tregs). Pts remain on study until initiation of systemic therapy due to radiographic disease progression, development of disease-related symptoms, withdraw of consent or clinical change that renders the patient unacceptable for further observation. Local therapy (e.g. surgery, radiation) during the observation period is permitted. Currently, 29 patients have been accrued at 5 collaborating sites. The target accrual of 50 pts provides adequate power for the primary descriptive endpoint as well as 80% power to detect changes from baseline for the correlate endpoints based on a two-sided Wilcoxon signed rank test.
Randomized, multicenter, two-dose level, open-label, phase IIa study with the intraperitoneally infused trifunctional bispecific antibody catumaxomab (anti-EpCAM × anti-CD3) to select the better dose level in platinum refractory epithelial ovarian cancer patients
Authors: A. Belau, J. Pfisterer, P. Wimberger, C. Kurzeder, A. Du Bois, J. Sehouli, S. Loibl, N. Burchardi, I. Vergote, U. Wagner
Journal: Journal of Clinical Oncology (2007)

5556 Background: The trifunctional antibody catumaxomab specifically binds EpCAM+ tumor cells, CD3+ T lymphocytes and accessory cells via the Fcγ RI/III thereby inducing a tumor specific cell mediated cytotoxicity in vitro and in vivo. This study was conducted to evaluate efficacy and safety of two different regimens of catumaxomab. Methods: Women with platinum-refractory (progressing during or ≤ 6 mos. after the last platinum containing regimen) epithelial ovarian cancer and measurable recurrent disease were randomized to receive either 10 -10 -10 - 10 μg or 10–20–50–100 μg of catumaxomab over 6h i.p on days 0, 3, 7 and 10. Results: 45 pts. were entered (22 high dose (HD)-arm, 23 low dose (LD)-arm). Both groups were well balanced concerning ECOG-perfomance score, with a median age of 65.6y in the HD- and 57.6y in the LD-arm and with a median diameter of measurable lesions of 90mm in the HD- and 104mm in the LD-arm. Based on the AEs, changes in laboratory parameters and other safety variables observed in the safety population in the course of this study, the accumulated safety experience is consistent with the key features of the mode of action of catumaxomab. Their intensity on median level was mostly mild to moderate. A clinical benefit was detectable in 27.3% of pts. for the HD- (1PR/5SD) and 8.7% of pts. for the LD-arm (2SD). After a median follow-up of 4.96 months, the median overall survival time was 182 d for the HD- and 114 d for the LD-arm. Conclusion: The results demonstrate that catumaxomab is safe with acceptable toxicity when administered as a sequence of 4 IP infusions at 10, 20, 50 and 100 μg. A modest dose effect is observed for the higher doses of catumaxomab. No significant financial relationships to disclose.
Effects of Liraglutide on Cardiovascular Outcomes in Patients With Diabetes With or Without Heart Failure
Authors: Steven P. Marso, Florian M.M. Baeres, Stephen C. Bain, Bryan Goldman, Mansoor Husain, Michael A. Nauck, Neil R. Poulter, Richard E. Pratley, Anne Bloch Thomsen, John B. Buse
Journal: Journal of the American College of Cardiology (2020)
Abstract P221: The Impact of Prevalent and New-onset Cardiometabolic Risk on the Incidence of Hepatic Steatosis
Authors: Ehimen C Aneni, Marcio S Bittencourt, Miguel Caínzos Achirica, Michael J Blaha, Ahmed M Soliman, Mouaz H Al-mallah, Matthew J Budoff, Raul Santos, Khurram Nasir
Journal: Circulation (2020)

Background: Little is known about hepatic steatosis (HS) incidence and its relationship to underlying or new-onset cardiometabolic risk. This study aims to assess the incidence of hepatic steatosis in an asymptomatic population and to determine its relationship to both prevalent and new-onset cardiometabolic risk factors. Methods: We analyzed retrospective data from a voluntary employer-sponsored routine health promotion evaluation at the Preventive Medicine Center of the Hospital Israelita Albert Einstein (São Paulo, Brazil) collected from October 2004 to December 2016.Medical and demographic history, anthropometric measures including blood pressure, body mass index (BMI) and waist circumference, and fasting blood samples were obtained. Participants also had ultrasonography to assess for HS. We included data from 8,448 individuals who had complete cardiometabolic and ultrasound data at baseline and repeated all tests at least 6 months later. Results: The mean age (standard deviation, SD) of participants was 40 (9) years. Over a mean (SD) follow-up of 3.4 (2.3) years, the incidence of HS was 14.7%. As shown in the table, diabetes, poor physical activity, elevated waist circumference and cigarette smoking at baseline were independently associated with hepatic steatosis. There was an additive effect of the increasing cardiometabolic risk factors (see graph) on the risk of developing HS. Participants with new-onset cardiometabolic risk factors also had a higher risk of incident HS after accounting for baseline demographics and cardiometabolic risk factors (see forest plot). This was most pronounced for incident obesity (BMI ≥ 30 Kg/m 2 ). Conclusion: In this relatively young population, the incidence of HS was high and was both independently and collectively associated with baseline cardiometabolic risk. New-onset cardiometabolic risk tracks with incident HS. This study emphasizes the need for assessing and mitigating cardiometabolic risk in the prevention of HS.
Abstract P418: Increased Pro-neurotensin/neuromedin N is Associated With Incident Ischemic Stroke
Authors: Charles D Nicoli, Nicholas Wettersten, George Howard, Virginia J Howard, Suzanne E Judd, Mary Cushman
Journal: Circulation (2020)

Introduction: The neuropeptide neurotensin (NT) has been linked to cardiovascular and metabolic disease risk. Through measurement of its stable equimolar precursor, pro-neurotensin/neuromedin N (pro-NT/NMN), hyperactivity of NT has been associated with aggregate cardiovascular outcomes that include stroke. However, the exclusive association of pro-NT/NMN with incident ischemic or hemorrhagic stroke has not been studied. Hypothesis: Higher serum pro-NT/NMN is associated with incident ischemic and hemorrhagic stroke. Methods: Prospective case-cohort study in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. From 2003-2007, REGARDS enrolled 30,239 White or Black adults aged ≥45. Pro-NT/NMN was measured by immunoassay in 464 ischemic stroke cases, 49 hemorrhagic stroke cases, and 800 non-cases from a random cohort. Cox proportional-hazards models were used to calculate hazard ratios (HR) of stroke by pro-NT/NMN quartiles and per standard deviation (SD) of log pro-NT/NMN. Model 1 (both stroke types) included demographic factors as covariates, Model 2A (ischemic only) added ischemic stroke risk factors, and Model 2B (hemorrhagic only) added hemorrhagic stroke risk factors. Results: The table shows an increased HR of ischemic stroke for those in the 4th vs 1st-quartile pro-NT/NMN in Model 1 with a trend of increased risk across quartiles; this was attenuated in Model 2A. Prebaseline diabetes and coronary artery disease were the largest confounders of ischemic stroke risk, with each accounting for 19% of the association observed in Model 1. There was no association of pro-NT/NMN with hemorrhagic stroke in either model. There were no interactions of race or sex with log pro-NT/NMN. Conclusions: Higher pro-NT/NMN is associated with increased risk of ischemic stroke after adjusting for demographics, but this was not independent of stroke risk factors. No significant association with hemorrhagic stroke was observed; this analysis was limited by a small number of events.
Lean methods: inappropriate for healthcare
Authors: Nick Mann
Journal: BMJ (2020)

In Smith and colleagues’ analysis in The BMJ ’s Quality Improvement series of infomercial articles, “Lean” is mentioned no less than 42 times.1 Lean seems to talk a lot about using Lean to talk about how to redefine “value” in healthcare.

Attempts to reduce the “commodity” of treating illness into standardised processes is inappropriate from the start. Productivity is an overarching theme—one which cannot apply to the value …
Targeting Chromosomal Architectural HMGB Proteins Could Be the Next Frontier in Cancer Therapy
Authors: Anirban Mukherjee, Karen M. Vasquez
Journal: Cancer Research (2020)

Abstract Chromatin-associated architectural proteins are part of a fundamental support system for cellular DNA-dependent processes and can maintain/modulate the efficiency of DNA replication, transcription, and DNA repair. Interestingly, prognostic outcomes of many cancer types have been linked with the expression levels of several of these architectural proteins. The high mobility group box (HMGB) architectural protein family has been well studied in this regard. The differential expression levels of HMGB proteins and/or mRNAs and their implications in cancer etiology and prognosis present the potential of novel targets that can be explored to increase the efficacy of existing cancer therapies. HMGB1, the most studied member of the HMGB protein family, has pleiotropic roles in cells including an association with nucleotide excision repair, base excision repair, mismatch repair, and DNA double-strand break repair. Moreover, the HMGB proteins have been identified in regulating DNA damage responses and cell survival following treatment with DNA-damaging agents and, as such, may play roles in modulating the efficacy of chemotherapeutic drugs by modulating DNA repair pathways. Here, we discuss the functions of HMGB proteins in DNA damage processing and their potential roles in cancer etiology, prognosis, and therapeutics.
Worry About Daily Financial Needs and Food Insecurity Among Cancer Survivors in the United States
Authors: Zhiyuan Zheng, Ahmedin Jemal, Reginald Tucker-Seeley, Matthew P. Banegas, Xuesong Han, Ashish Rai, Jingxuan Zhao, K. Robin Yabroff
Journal: Journal of the National Comprehensive Cancer Network (2020)

A cancer diagnosis can impose substantial medical financial burden on individuals and may limit their ability to work. However, less is known about worry for nonmedical financial needs and food insecurity among cancer survivors.The National Health Interview Survey (2013-2017) was used to identify cancer survivors (age 18-39 years, n=771; age 40-64 years, n=4,269; age ≥65 years, n=7,101) and individuals without a cancer history (age 18-39 years, n=53,262; age 40-64 years, n=60,141; age ≥65 years, n=30,261). For both cancer survivors and the noncancer group, adjusted proportions were generated for (1) financial worry ("very/moderately/not worried") about retirement, standard of living, monthly bills, and housing costs; and (2) food insecurity ("often/sometimes/not true") regarding whether food would run out, the fact that food bought did not last, and the inability to afford balanced meals. Further adjusted analyses examined intensity measures ("severe/moderate/minor or none") of financial worry and food insecurity among cancer survivors only.Compared with individuals without a cancer history, cancer survivors aged 18 to 39 years reported consistently higher "very worried" levels regarding retirement (25.5% vs 16.9%; P<.001), standard of living (20.4% vs 12.9%; P<.001), monthly bills (14.9% vs 10.3%; P=.002), and housing costs (13.6% vs 8.9%; P=.001); and higher "often true" levels regarding worry about food running out (7.9% vs 4.6%; P=.004), food not lasting (7.6% vs 3.3%; P=.003), and being unable to afford balanced meals (6.3% vs 3.4%; P=.007). Findings were not as consistent for cancer survivors aged 40 to 64 years. In contrast, results were generally similar for adults aged ≥65 years with/without a cancer history. Among cancer survivors, 57.6% (age 18-39 years; P<.001), 51.9% (age 40-64 years; P<.001), and 23.8% (age ≥65 years; referent) reported severe/moderate financial worry intensity, and 27.0% (age 18-39 years; P<.001), 14.8% (age 40-64 years; P<.001), and 6.3% (age ≥65 years; referent) experienced severe/moderate food insecurity intensity. Lower income and higher comorbidities were generally associated with greater intensities of financial worry and food insecurity in all 3 age groups.Younger cancer survivors experience greater financial worry and food insecurity. In addition to coping with medical costs, cancer survivors with low income and multiple comorbidities struggle to pay for daily living needs, such as food, housing, and monthly bills.