tbuckley/cabot-search huggingface dataset:
Reduced BMP signaling in lungs of mechanically ventilated newborn mice as potential treatment target for neonatal chronic lung disease
Authors: Markus Koschlig, Xuefei Tian, Deepti Sudheendra, Edda Spiekerkoetter, Anne Hilgendorff
Journal: European Respiratory Journal (2014)

Background: Neonatal chronic lung disease (CLD) is characterized by impaired lung development, leading to oxygen dependency and vascular remodeling. We investigated the role of the bone morphogenetic protein receptor 2 (BMPR2) signaling pathway which is critical for vascular development in a mouse model of CLD. We hypothesized that the BMPR2 activator FK506, recently found to reduce endothelial apoptosis and increase endothelial tube formation, might be beneficial in neonatal CLD.

Methods: In a mouse model of CLD, 5-6 day old C57B6 mice were mechanically ventilated for 2h and 8h with 40% oxygen (MV-O2) and compared to non-ventilated controls (n=4/group). Protein expression of phosphoSmad1/5/8 as well as Id1, a downstream target of BMPR2, was measured in whole lung lysates by western-immunoblotting. In vitro , human fetal endothelial cells (ECs) were exposed to 40% hyperoxia for 24 h and treated with BMP6, FK506, TGF beta or the combination of both (n=3 each group). BMPR2 and Id1 expression were assessed by qRT-PCR.

Results: MV-O2 for 8h significantly reduced phosphoSmad1/5/8 as well as Id1 protein expression in total lung lysates (p< 0.01). In line with this, hyperoxia significantly decreased BMPR2 as well as Id1 mRNA expression in human fetal ECs. This effect was prevented by BMP6 treatment, leading to a 2- to 4-fold increase in BMPR2 and Id1 mRNA expression. FK506 partially restored BMPR2 and fully restored Id1 mRNA expression with more pronounced effects in the presence of TGF beta.

Conclusion: Modulating BMPR2 signaling in neonatal CLD might be a promising strategy to improve impaired vasculogenesis in the course of the disease.
Epinephrine Administration and Pediatric In-Hospital Cardiac Arrest
Authors: Alison Poulton, Frank Chen, Ralph Nanan
Journal: JAMA (2016)

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Abstract 9528: Excellent Mid-Term Outcomes in Asymptomatic patients with Mitral Regurgitation: A Case for Early Intervention
Authors: Robin Varghese, Anelechi C Anyanwu, Shinobu Itagaki, David H Adams
Journal: Circulation (2012)

Objective: To assess outcomes of mitral valve repair surgery stratified by a patient's ACC/AHA guideline indication for surgery. Methods: Between May 2003 and December 2010 data was collected on 645 consecutive elective patients with degenerative severe mitral valve regurgitation who underwent mitral valve repair surgery (MVRr). Study patients were stratified into and subsequently analyzed as three cohorts based on the ACC/AHA guidelines: Group 1: Asymptomatic patients without ACC/AHA echocardiographic or clinical triggers for surgery (133 patients), Group 2: Asymptomatic patients with at least one ACC/AHA echocardiographic or clinical trigger for surgery (135 patients), and Group 3: Symptomatic patients with or without ACC/AHA echocardiographic triggers for surgery (377 patients). Echocardiographic parameters and survival were measured during the follow up period. Results: Patient follow up was 100%. Mean age was 54.4 +/- 12.2 years, 56.2 +/- 10.7, and 58.2 +/- 14.2 in groups 1, 2, and 3 respectively (p=0.013). Preoperative comorbidities were similar in the three groups. A 100% repair rate was achieved in the series. 30-day operative mortality was 0% (0/133) in group 1, 0% (0/135) in group 2 and 1.1% (4/377) in group 3 (p=0.24). Mean preoperative ejection fraction was expectantly different between the cohorts: Group 1; 64% +/- 5%, group 2; 58% +/- 7%, and group 3; 60% +/- 8% (p=0.001). Echocardiographic follow-up ranged from 0.07 -100 months with mean follow up of 2.2 years. The overall survival at 8 years was: Group 1; 100%, group 2; 100%, and group 3; 91% +/- 3%. Freedom from moderate MR at 8 years was: Group 1; 93% +/- 4%, group 2; 86% +/- 3%, and group 3; 88% +/- 3%. Conclusions: Early mitral valve repair can be offered to patients with near 100% likelihood of repair and low morbidity. Early repair had a trend to a better freedom from moderate MR at 8 years. At expert centers, early mitral valve repair surgery should be offered to asymptomatic patients without echocardiographic or clinical triggers.
Intronic gene conversion in the evolution of human X-linked color vision genes.
Authors: S K Shyue, L Li, B H Chang, W H Li
Journal: Molecular Biology and Evolution (1994)

Human red and green visual pigment genes are X-linked duplicate genes. To study their evolutionary history, introns 2 and 4 (1,987 and 1,552 bp, respectively) of human red and green pigment genes were sequenced. Surprisingly, we found that intron 4 sequences of these two genes are identical and that the intron 2 sequences differ by only 0.3%. The low divergences are unexpected because the duplication event producing the two genes is believed to have occurred before the separation of the human and Old World monkey (OWM) lineages. Indeed, the divergences in the two introns are significantly lower than both the synonymous divergence (3.2% +/- 1.1%) and the nonsynonymous divergence (2.0% +/- 0.5%) in the coding sequences (exons 1-6). A comparison of partial sequences of exons 4 and 5 of human and OWM red and green pigment genes supports the hypothesis that the gene duplication occurred before the human-OWM split. In conclusion, the high similarities in the two intron sequences might be due to very recent gene conversion, probably during evolution of the human lineage.
Abstract 140: Comparison of CPR Quality Metrics Before and After Placement of Advanced Airways in Out-of-Hospital Cardiac Arrest
Authors: Eric Helfenbein, Saeed Babaeizadeh, Mohamud Daya, Bentley Bobrow, Bruce Barnhart, Guillermo Haro, Daniel Spaite
Journal: Circulation (2013)

Background: The value and role of advanced airway placement (AAP) (tracheal intubation and supraglottic airways) during out-of-hospital cardiac arrest (OHCA) is debatable and little is known about ...
Abstract P192: Lipoprotein(a) is Significantly Associated with ApoB-containing Atherogenic Lipoproteins in African Americans
Authors: Enkhmaa Byambaa, Anuurad Erdembileg, Wei Zhang, Lars Berglund
Journal: Circulation (2012)

Background: Lipoprotein(a), Lp(a), is a genetically regulated independent cardiovascular risk factor, where levels differ across ethnicity. The relationship between Lp(a) and apolipoprotein B (apoB)-containing atherogenic lipoproteins across ethnicity is not well understood. Objective: To investigate the associations of Lp(a) levels with other apoB-containing lipoproteins with a focus on ethnicity. Methods: Plasma lipid and lipoproteins were measured in 336 Caucasians and 224 African Americans undergoing coronary angiography. Lp(a) levels were determined using an apo(a) size insensitive sandwich ELISA. Values for Lp(a) and triglyceride (TG) were square root or logarithmically transformed before analyses. Total and low density lipoprotein (LDL) cholesterol, and apoB levels were corrected for contribution of Lp(a) using previously published algorithms. Values are given mean ± standard deviation or median (interquartile range) for normally or non-normally distributed variables, respectively. Results: Levels of total and LDL cholesterol and apoB-100 did not differ between Caucasians and African Americans. As expected, African Americans had significantly higher levels of Lp(a) [110 (60-180) nmol/l vs. 24 (7-79) nmol/l, p&lt;0.001] and high density lipoprotein (HDL) cholesterol (49±17 mg/dl vs. 41±12 mg/dl, p&lt;0.001), as well as significantly lower levels of TG [106 (80-144) mg/dl vs. 153 (114-222) mg/dl, p&lt;0.001] compared to Caucasians. For both ethnic groups, Lp(a) levels were significantly and positively correlated with total cholesterol (p&lt;0.005 for Caucasians and p&lt;0.001 for African Americans), LDL cholesterol (p&lt;0.001 for both groups), apoB100 (p&lt;0.05 for Caucasians and p&lt;0.001 for African Americans) and apoB/apoA-1 ratio (p&lt;0.05 for Caucasians and p&lt;0.001 for African Americans). However, when adjusted for the corresponding contribution of Lp(a) to the levels of these parameters, the associations remained significant in African Americans (p&lt;0.05 for total cholesterol; p&lt;0.05 for LDL cholesterol; p&lt;0.001 for apoB100, respectively), but not in Caucasians. Conclusion: Although total and LDL cholesterol, and apoB100 levels were comparable in African Americans and Caucasians, the associations of these parameters with Lp(a) levels differed across ethnicity. For African Americans, but not for Caucasians, associations of all three parameters with Lp(a) remained significant after appropriate adjustments. The findings suggest an interethnic difference in the relation between Lp(a) and other plasma apoB-containing lipoprotein levels, with a closer relationship among African Americans.
The impact of IMC nodal drainage on primary breast cancer outcome
Authors: A. L. Kong, K. K. Hunt, M. Yi, K. Weatherspoon, I. Bedrosian, W. Tereffe, R. Hwang, M. I. Ross, T. A. Buchholz, F. Meric-Bernstam
Journal: Journal of Clinical Oncology (2008)

534 Background: Involvement of the internal mammary node chain (IMC) portends a poor prognosis in primary breast cancer. Theoretically, internal mammary node involvement cannot be present in the absence of primary tumor lymphatic drainage to these nodes. We examined whether the presence of IMC drainage negatively impacted regional and systemic recurrence and overall survival (OS). Methods: We performed a retrospective review of a prospective surgical database of patients with invasive breast cancer (Stage I-III) who underwent preoperative lymphoscintigraphy (LSG) with peritumoral injection and subsequent intraoperative lymphatic mapping from 1996-2002. The study was limited to 1,854 patients who demonstrated drainage on LSG and did not undergo IMC nodal biopsy. Medical records were reviewed for demographics, clinicopathologic data, and medical and surgical treatment data. Outcomes were evaluated including regional and systemic recurrence and overall survival (OS). Patients with any IMC drainage (IM+, alone or with axillary drainage) were compared to those without IMC drainage (IM-) as identified on LSG. Median follow-up was 57.9 months. Results: Three hundred forty-four (18.5%) patients showed IM drainage. Patients with IM drainage were younger and less likely to have upper outer quadrant tumors than those with non-IM drainage (p< 0.0001 for both). Tumor size and axillary sentinel node status were not significantly different between both groups (p=0.08 and p=0.39, respectively). There was no difference in IM irradiation rates of patients who were IM+ versus patients who were IM-. The 5-year systemic recurrence rate was 3.8% for IM+ patients and 2.1% for IM- patients (p=0.07). The 5-year regional recurrence rate was 0.9% for IM+ patients and 0.5% for IM- patients (p=0.46). Only one patient recurred in the IM nodal chain. There was no statistically significant difference in the 5-year OS rates of IM+ versus IM- patients in the entire study cohort as well as in the axillary node positive patients. Conclusions: A finding of IM drainage on LSG was not a significant predictor of OS during this study period. This finding needs to be confirmed at longer follow-up. Further studies are needed to determine the role of the IM sentinel node biopsy. No significant financial relationships to disclose.
Initial phase II results with crizotinib in advanced <i>ALK</i>-positive non-small cell lung cancer (NSCLC): PROFILE 1005.
Authors: L. Crinò, D. Kim, G. J. Riely, P. A. Janne, F. H. Blackhall, D. R. Camidge, V. Hirsh, T. Mok, B. J. Solomon, K. Park, S. M. Gadgeel, R. Martins, J. Han, T. M. De Pas, A. Bottomley, A. Polli, J. Petersen, V. R. Tassell, A. T. Shaw
Journal: Journal of Clinical Oncology (2011)

7514 Background: The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a subset of NSCLC patients (pts). Crizotinib is a potent, selective, ATP-competitive, small molecule ALK inhibitor. Pts with ALK-rearranged NSCLC had a high response rate to crizotinib in a prior expanded cohort study. Methods: This ongoing study included pts from 57 sites in 12 countries with ALK-rearranged NSCLC (by centralized FISH test) who progressed after ≥1 chemotherapy for recurrent/advanced/metastatic disease (including treated brain metastases). Pts received oral crizotinib 250 mg BID continuously in 3-week cycles. Disease response was evaluated by RECIST 1.1 every 6 weeks and safety/patient-reported outcomes (PRO; by EORTC QLQ-C30/QLQ-LC13 v3) were evaluated every 3 weeks. Results: Currently, 136 pts are evaluable for safety, 109 for PRO, and 76 for tumor response. Median age was 52 years, 94% had adenocarcinoma, 68% had never smoked, and 53% were female. Most pts (93%) had ≥2 prior chemotherapy regimens (range 1–11). Pts received a median 9 weeks of treatment (range 1–13 cycles started) and 88% remain on therapy. On a waterfall plot of tumor measurements in evaluable pts, 63 of 76 pts (83%) had target lesion shrinkage (41 pts had ≥30% shrinkage). Seven patients experienced objective progression by RECIST. The most frequent treatment-related AEs were nausea (46%), vision disorder (45%), vomiting (39%), and diarrhea (29%), mostly Grade 1/2. Treatment-related Grade 3/4 AEs were reported in 15% of pts (mostly increased ALT, dyspnea, and neutropenia). Two of the 9 deaths on-study were considered treatment-related (pneumonitis, unknown cause). Most pts had completed 4 PRO assessments by this review, with clinically significant (≥10 points) improvements in pain, cough, dyspnea and fatigue seen as early as cycle 2. Only a clinically significant increase in constipation was reported by patients over the course of therapy. Overall, quality of life was maintained. Conclusions: Data from a second global clinical study suggest crizotinib was safe and well-tolerated with preliminary evidence of improved symptoms and clinically meaningful antitumor activity in pts with pre-treated ALK-rearranged NSCLC.
Should doctors practise resuscitation skills on newly deceased patients? A survey of public opinion
Authors: Sapal Tachakra, Selwyn Ho, Maria Lynch, Roger Newson
Journal: Journal of the Royal Society of Medicine (1998)

Trainee doctors must acquire skills in resuscitation, but opportunities for learning on real patients are limited. One option is to practise these skills in newly deceased patients. We sought opinions from 400 multiethnic guests at an open-access dinner dance for members of a local community. The questionnaire could elicit the responses strongly agree, agree, unsure, disagree or strongly disagree. 332 (83%) guests responded. For non-invasive techniques, 32% of responders supported practice without consent, 74% with consent. Support diminished with increasing invasiveness of procedure. 91% of the sample were uncomfortable about the procedures, the commonest reason being 'respect for the body' (264/302). 86% of responders felt that practice should last for no more than 5 minutes. The most popular solutions were for people to carry a personal card giving consent (89%) and establishment of a central register of individuals consenting to be practised upon after death (79%).
The importance of etoposide dose intensity in the management of metastatic germ cell tumours and the role of paclitaxel in salvage treatment of relapsing patients
Authors: S. A. North, S. Marwaha, P. M. Venner
Journal: Journal of Clinical Oncology (2006)

14502 Background: The primary objective was to evaluate the effect of etoposide dose intensity in the standard cisplatin/etoposide/bleomycin (PEB) regimen on progression free (PFS) and overall survival (OS). Secondary objectives were and to determine how the addition of paclitaxel in salvage regimens impacts OS and to compare the risk distribution of germ cell patients seen at a tertiary care centre to that quoted in the International Germ Cell Consensus Classification (IGCCC). Methods: A retrospective chart review of all 302 germ cell patients requiring cisplatin-based chemotherapy between January 1980 and December 2004 was conducted. Data collected on initial treatment included the dose of etoposide: 500 mg/m 2 /cycle (E500) or 360 mg/m 2 /cycle (E360) and whether the salvage treatment contained paclitaxel or not. PFS and OS were calculated. Patients were risk stratified as per IGCCC variables. Results: In the PEB regimen, E500 is superior to E360 as it results in a relapse rate of only 3% and an overall survival of 97% compared to a relapse rate and survival of 29% and 80% respectively. The addition of paclitaxel to salvage chemotherapy regimens for patients relapsing results in 1/5 (20%) of patients dying compared to 26/39 (67%) for those receiving a non-paclitaxel based salvage regimen. The distribution of seminoma patients was similar to the IGCCC (90% good risk, 10% intermediate risk). Non-seminoma (NS) patients were skewed to the good-risk category: 71% good risk, 10% intermediate risk and 18% poor risk as compared to 56%, 28% and 16% respectively as reported by the IGCCC. 5-year PFS and OS were comparable to those documented by the IGCCC with the exception of the intermediate risk NS patients where our 5 year PFS was 48% compared to 75% expected but 5 year OS was similar in these patients (75% Vs. 80%). Conclusions: This review demonstrates that PEB treatment containing higher dose etoposide is superior in terms of PFS and OS. Although the sample size is small it appears that Paclitaxel containing salvage regimens results in superior outcomes compared to previously used salvage regimens. Our centre has a similar risk distribution of patients as that quoted by the IGCCC. No significant financial relationships to disclose.
Improving the quality of abstracts for economic analyses (EA) in oncology.
Authors: M. Y. Ho, K. K. Chan, M. C. Cheung, S. Peacock, W. Y. Cheung
Journal: Journal of Clinical Oncology (2010)

e16546 Background: Increasing costs of cancer drugs underscore the importance of EA, which convey key information about the relative costs and benefits of new interventions. While guidelines for abstracts exist for oncology clinical trials, similar recommendations for EA are lacking. Our objectives were to 1) identify items considered by experts to be essential for EA abstracts, 2) evaluate the quality of EA abstracts submitted to ASCO, ASH, and ISPOR meetings, and 3) propose guidelines for future reporting. Methods: Health economic experts were surveyed and asked to rate each of 24 possible EA elements on a 5-point Likert scale. A scoring system for abstract quality (0=poor and 100=excellent) was devised based on EA elements with an average expert rating ≥ 3.5. All EA abstracts from ASCO (‘97–‘09), ASH (‘04–‘09), and ISPOR (‘97–‘09) were reviewed and assigned a quality score. Results: Of 99 experts surveyed, 51 (52%) responded. Characteristics of respondents: average age = 53; male = 78%; US/Europe/Canada = 54%/28%/18%. A total of 216 abstracts were reviewed: ASCO 53%, ASH 14%, and ISPOR 33%. Median quality score was 75 (range 48 to 93), but notable deficiencies were observed. For instance, the cost perspective of the EA was reported in only 61% of abstracts, while the time horizon was described in only 47%. An association was seen between year of presentation and overall quality of abstracts (p=0.001), with those from recent years demonstrating better quality scores. There were also disparities in quality scores among EA of different cancer sites (p=0.005). Conclusions: Quality of EA abstracts for oncology has improved over time, but there is room for improvement. Abstracts may be enhanced using guidelines derived from our survey of experts (see Table). Items that are absolutely essential Type of EA (cost-utility, cost-benefit) Description of intervention Description of comparator Items that should be reported Target population for intervention Time horizon Perspective Method in which denominator (LYG, QALY) was derived Cost-effectiveness ratio Conclusion about cost-effectiveness of intervention Currency Items that may be reported if space permits Background of cost problem Costs that were included Sensitivity analysis Setting of study Discounting No significant financial relationships to disclose.
Ventilatory and haemodynamic noninvasive assessment during resistance exercise in coronary arterial disease patients
Authors: Flavia Cristina Rossi Caruso, Junior Jose Carlos Bonjorno, Vivian Maria Arakelian, Daniela Bassi Dutra, Renata Gonçalves Mendes, Bruno Archiza, Milena Pelosi Sperling, Renata Trimer, Aparecida Maria Catai, Audrey Borghi-Silva
Journal: European Respiratory Journal (2013)

Background: Studies have shown that resistance exercise (RE) the anaerobic threshold (AT) is 30% of maximal repetition (MR) in elderly, which would be a safe intensity of RE in this population and cardiac patients. RE have been applied in moderate to high intensities in order to increase muscle strength in CAD patients. However, the magnitude of ventilatory, metabolic and cardiovascular responses were not compared in these intensities (AT - moderate-to-high). Objectives: Compare ventilatory, cardiovascular and metabolic responses during discontinuous exercise testing (DRET) at AT vs maximal sustained load (MSL) obtained. Methods: Fifteen patients with CAD performed DRET until MSL of peripheral muscles on a leg press 45. Respiratory gas exchange (VO2, VCO2) and haemodynamic variables (heart rate (HR), cardiac output (CO), systolic volume (SV), cardiac index (CI)) were measured by cardioimpedance. Systolic (SBP) and diastolic blood pressure (DBP), dyspnea scores and ectopic beats were compared. Results: AT was obtained at 30% RM. As expected, ventilatory responses were higher in 60% than 30%. HR was 44,9% higher in 60% as well as CO (11%), SV (56%), CI (53%) and double product was 47% when compared to 30%. SBP, DBP and Borg magnitude were higher in the 60% when compared with 30% (P