tbuckley/cabot-search huggingface dataset:
Therapeutic profile of single-fraction radiosurgery of vestibular schwannoma: unrelated malignancy predicts tumor control
Authors: B. Wowra, A. Muacevic, C. Furweger, C. Schichor, J.-C. Tonn
Journal: Neuro-Oncology (2012)

Radiosurgery has become an accepted treatment option for vestibular schwannomas. Nevertheless, predictors of tumor control and treatment toxicity in current radiosurgery of vestibular schwannomas are not well understood. To generate new information on predictors of tumor control and cranial nerve toxicity of single-fraction radiosurgery of vestibular schwannomas, we conducted a single-institution long-term observational study of radiosurgery for sporadic vestibular schwannomas. Minimum follow-up was 3 years. Investigated as potential predictors of tumor control and cranial nerve toxicity were treatment technology; tumor resection preceding radiosurgery; tumor size; gender; patient age; history of cancer, vascular disease, or metabolic disease; tumor volume; radiosurgical prescription dose; and isodose line. Three hundred eighty-six patients met inclusion criteria. Treatment failure was observed in 27 patients. History of unrelated cancer (strongest predictor) and prescription dose significantly predicted tumor control. The cumulative incidence of treatment failure was 30% after 6.5 years in patients with unrelated malignancy and 10% after ≥15 years in patients without such cancer (P < .02). Tumor volume was the only predictor of trigeminal neuropathy (observed in 6 patients). No predictor of facial nerve toxicity was found. On the House and Brackmann scale, 1 patient had a permanent one-level drop and 7 a transient drop of 1 to 3 levels. Serviceable hearing was preserved in 75.1%. Tumor hearing before radiosurgery, recurrence, and prescription isodose predicted ototoxicity. Unrelated malignancy is a strong predictor of tumor control. Tumor recurrence predominantly predicts ototoxicity. These findings potentially will aid future clinical decision making in ambiguous cases.
Self-expending metallic Y-stent for complex malignant lesions of the main carina
Authors: Samy Lachkar, Mathieu Salaun, Suzanna Bota, Luc Thiberville
Journal: European Respiratory Journal (2013)

Introduction: Silicon Y-stents are commonly used to manage malignant disease of the carina, but remains often inadequate to address complex stenosis or tracheo-oesophageal fistula.  Objective: To assess the use of self-expending metallic Y-stent, and to evaluate symptoms relief and tolerance in patients with malignant tumors of the main carina, not suitable for silicon stenting and surgical curative treatment.  Methods: 8 patients with complex stenosis due to lung cancer received metallic Y tracheal stents, and 4 patients with oesophageal cancer with complex fistula involving the carina and left main bronchus had both metallic oesophageal and Y tracheal stents. Stents were placed under general anaesthesia using rigid-bronchoscopy with guide-wire fluoroscopy guidance. Respiratory symptoms, symptom-free and overall survival were recorded.  Results: Self-expending metallic Y-stent were easily placed in each case, with a procedure median duration of 30 min. All patients experienced symptoms improvement, with a median symptom-free survival of 32 days (1 to 273 d.). Among patients with oesophago-tracheal fistula, only one had a fistula extension on follow-up needing re-stenting, while two patients reported symptom resolution until death (at 6 and 9 months), and one remains symptom-free at 1 month, allowing oral nutrition. In lung cancer-related stenosis patients, the median symptom-free survival was 28 d. (interquartile range (IQR): 17-56 d.), and median survival 30 d. (IQR: 17-57 d.).  Conclusion: Self-expanding metallic Y-stents appear easy to use and provide symptoms improvement in patients with complex malignant diseases of the main carina that are not suitable for curative treatment or silicon stenting.
Obesity as Compared With Physical Activity in Predicting Risk of Coronary Heart Disease in Women
Authors: Tricia Y. Li, Jamal S. Rana, JoAnn E. Manson, Walter C. Willett, Meir J. Stampfer, Graham A. Colditz, Kathryn M. Rexrode, Frank B. Hu
Journal: Circulation (2006)

Background— The comparative importance of physical inactivity and obesity as predictors of coronary heart disease (CHD) risk remains unsettled. Methods and Results— We followed 88 393 women, 34 to 59 years of age, in the Nurses’ Health Study from 1980 to 2000. These participants did not have cardiovascular disease and cancer at baseline. We documented 2358 incident major CHD events (including nonfatal myocardial infarction and fatal CHD) during 20 years of follow-up, including 889 cases of fatal CHD and 1469 cases of nonfatal myocardial infarction. In a multivariate model adjusting for cardiovascular risk factors, overweight and obesity were significantly associated with increased risk of CHD, whereas increasing levels of physical activity were associated with a graded reduction in CHD risk ( P &lt;0.001). In joint analyses of body mass index (BMI) and physical activity in women who had a healthy weight (BMI, 18.5 to 24.9 kg/m 2 ) and were physically active (exercise ≥3.5 h/wk) as the reference group, the relative risks of CHD were 3.44 (95% confidence interval [CI], 2.81 to 4.21) for women who were obese (BMI ≥30 kg/m 2 ) and sedentary (exercise &lt;1 h/wk), 2.48 (95% CI, 1.84 to 3.34) for women who were active but obese, and 1.48 (95% CI, 1.24 to 1.77) for women who had a healthy weight but were sedentary. In combined analyses of waist-hip ratio and physical activity, both waist-hip ratio and physical activity were significant predictors of CHD, and the highest risk was among women in the lowest category of physical activity and the highest tertile of waist-hip ratio (relative risk=3.03; 95% CI, 1.96 to 4.18). Even a modest weight gain (4 to 10 kg) during adulthood was associated with 27% (95% CI, 12% to 45%) increased risk of CHD compared with women with a stable weight after adjusting for physical activity and other cardiovascular risk factors. Conclusions— Obesity and physical inactivity independently contribute to the development of CHD in women. These data underscore the importance of both maintaining a healthy weight and regular physical activity in preventing CHD.
Elevated plasma EPCR levels early post ICU admission predict sepsis development
Authors: Alice Vassiliou, Anastasia Kotanidou, Nikolaos Maniatis, Zafeiria Mastora, Panagiota Albani, Ioanna Dimopoulou, Apostolos Armaganidis, Charalambos Roussos, Stylianos Orfanos
Journal: European Respiratory Journal (2012)

Introduction   The endothelial protein C receptor (EPCR) mediates coagulation and inflammation. Early rise of circulating soluble (s)EPCR levels has been shown to correlate with poor outcome in critically-ill patients with severe sepsis (Guitton  et al . Intensive Care Med 2011; 37: 950-6); yet potential associations of sEPCR measured early post ICU admission with subsequent sepsis development are still unknown.   Aims    To investigate if sEPCR plasma levels of critically-ill subjects at ICU admission predict sepsis development.   Methods   59 critically-ill patients suffering from medical, surgical and trauma-related pathologies were included in the study. Circulating sEPCR levels were measured ≤24h post ICU admission; all patients were free of sepsis. Demographics, APACHE II & SOFA scores were recorded and circulating PCT & CRP were measured.   Results   From the initial cohort, 30 patients subsequently developed sepsis and 29 did not. SOFA score (mean±SD: 6.4±2.7) and sEPCR levels (median & IQR: 173.4 (104.5-223.5) ng/mL) were significantly higher in the subsequent sepsis group as compared to the non sepsis group (5±2.3, p=0.037, and 98.3 (69.8-147.7) p=0.004, respectively). ICU mortality and PCT tended to be higher in the sepsis group. Cox regression analysis identified sEPCR as the only parameter related to sepsis development with time (RR: 1.078 & 95% CI: 1.016-1.144, by 10 sEPCR units, p=0.013). When the whole cohort was dichotomized above (≥139.5) and below the sEPCR median (   Conclusions   In our cohort, high sEPCR plasma levels at ICU admission (i.e. ≤24h) predict sepsis development.
A randomized phase II trial of irinotecan in combination with infusional or two different bolus 5-fluorouracil and folinic acid regimens as first-line therapy for advanced colorectal cancer
Authors: K. Bouzid, S. Khalfallah, J. Tujakowski, B. Piko, G. Purkalne, S. Plate, P. Padrik, M. Serafy, E.M. Pshevloutsky, B. Boussard
Journal: Annals of Oncology (2003)
Clinical outcomes in women with breast cancer and a PALB2 mutation: a prospective cohort analysis
Authors: Cezary Cybulski, Wojciech Kluźniak, Tomasz Huzarski, Dominika Wokołorczyk, Aniruddh Kashyap, Anna Jakubowska, Marek Szwiec, Tomasz Byrski, Tadeusz Dębniak, Bohdan Górski, Victoria Sopik, Mohammad R Akbari, Ping Sun, Jacek Gronwald, Steven A Narod, Jan Lubiński
Journal: The Lancet Oncology (2015)
Origin, Evolution, and Biological Role of miRNA Cluster in DLK-DIO3 Genomic Region in Placental Mammals
Authors: E. A. Glazov, S. McWilliam, W. C. Barris, B. P. Dalrymple
Journal: Molecular Biology and Evolution (2008)

MicroRNAs (miRNAs) are a rapidly growing family of small regulatory RNAs modulating gene expression in plants and animals. In animals, most of the miRNAs discovered in early studies were found to be evolutionarily conserved across the whole kingdom. More recent studies, however, have identified many miRNAs that are specific to a particular group of organisms or even a single species. These present a question about evolution of the individual miRNAs and their role in establishing and maintaining lineage-specific functions and characteristics.
UK paediatrician is criticised over handling of baby's death
Authors: C. Dyer
Journal: BMJ (2014)

A consultant paediatrician has been criticised in a serious case review into the death of an 8 week old baby for failing to give police a firm opinion that the child was probably a victim of a criminal assault, inadvertently delaying a homicide investigation.1

The unnamed doctor arrived at Northampton General Hospital’s emergency department at 7 am on 17 March 2012 in response to a call after Jamie Kightley was brought to the hospital dead. Under the procedure for handling sudden unexpected deaths of children he became the “responsible paediatrician” and should have coordinated a multiagency …
High-frequency oscillatory ventilation and acute respiratory distress syndrome: at the crossroads?
Authors: Matt P Wise, Anton G Saayman, Michael A Gillies
Journal: Thorax (2013)

Acute respiratory distress syndrome (ARDS) was characterised by Ashbaugh and colleagues1 nearly half a century ago, and yet, to the casual observer, it might appear that little progress has been made since. Clinicians are still struggling with how best to define and treat ARDS.2 ,3 A major advance was the recognition that mechanical ventilation may induce further lung injury and the application of so-called lung protective ventilation (6 ml/kg ideal body weight tidal volumes and plateau pressures <30 cm H2O) reduces mortality.4 High-frequency oscillatory ventilation (HFOV) is an attractive mode of ventilation because it combines improved lung recruitment with small tidal volumes, often below anatomical dead space, applied at very high frequency. Thus, it theoretically provides ultra-lung protective ventilation, limiting atelectrauma (caused by cyclical alveolar opening and closing) and volutrauma (alveolar over-distension). For those not familiar with this mode of ventilation, it should be noted that, unlike conventional ventilation, increasing the frequency of HFOV reduces CO2 elimination. HFOV has often been used as a rescue therapy for severe ARDS and refractory hypoxaemia; however, uncertainty remains over its role in early ARDS. Although there is substantial experimental data, clinical studies are limited to case series and two small trials5 ,6 where controls did not receive what is now accepted as standard lung protective ventilation following the ARDSNet study.4

Two recently randomised clinical trials sought to establish if HFOV could reduce mortality in early ARDS.7 ,8 The UK-based OSCAR study7 randomised 795 patients to receive either HFOV or conventional ventilation. No difference was observed in 30 day mortality between groups (41.7% vs 41.1%, respectively). The larger OSCILLATE study8 planned to recruit 1200 patients but was stopped after 548 patients on recommendation from the data monitoring committee, as in-hospital mortality was significantly higher …
Regional structure-function correlations in chronic obstructive lung disease measured with positron emission tomography.
Authors: L H Brudin, C G Rhodes, S O Valind, P D Buckingham, T Jones, J M Hughes
Journal: Thorax (1992)

BACKGROUND: Positron emission tomography, performed with isotopes of very short half life, can be used to relate local lung tissue density to local ventilation and to the ventilation:perfusion ratio. This method has been used in 10 patients with severe chronic airflow obstruction and differing values for carbon monoxide transfer factor (TLCO) and transfer coefficient (KCO). METHODS: Ventilation (VA) and the ventilation:perfusion ratio (V/Q), lung density, and blood volume were measured regionally in a single transaxial section at mid-heart level with the patients in a supine position. Alveolar volume, extravascular tissue lung density, and perfusion (Q) were derived. Twenty five regions with abnormalities in the ventilation images were analysed. RESULTS: Tissue density showed a negative correlation with the ratio V/Q (r = 0.55) and a positive correlation with Q (r = 0.59) and blood volume (r = 0.65). In four patients with a low carbon monoxide transfer factor (TLCO) and transfer coefficient (KCO) &lt; 50% predicted many regions with low VA had low tissue density and normal or high V/Q. On the other hand, in four patients with TLCO and KCO &gt; 50% predicted many regions with low VA had normal or high tissue density and low values of V/Q. The other two patients had patterns between these two extremes. Individual ratios between mean values of tissue density and V/Q had a positive correlation with KCO (% pred; r = 0.79). CONCLUSIONS: These findings link structural differences with distinctive functional patterns; they reinforce the view that bronchial inflammation or oedema predominate in some patients with chronic airflow obstruction, whereas alveolar destruction is the major feature in others.
The Matricellular Protein CCN1 Is Essential for Cardiac Development
Authors: Fan-E Mo, Lester F. Lau
Journal: Circulation Research (2006)

The matricellular protein CCN1 (formerly named CYR61) regulates cell adhesion, migration, proliferation, survival, and differentiation through binding to integrin receptors and heparan sulfate proteoglycans. Here we show that Ccn1 -null mice are impaired in cardiac valvuloseptal morphogenesis, resulting in severe atrioventricular septal defects (AVSD). Remarkably, haploinsufficiency for Ccn1 also results in delayed formation of the ventricular septum in the embryo and persistent ostium primum atrial septal defects (ASD) in ≈20% of adults. Mechanistically, Ccn1 is not required for epithelial-to-mesenchymal transformation or cell proliferation and differentiation in the endocardial cushion tissue. However, Ccn1 deficiency leads to precocious apoptosis in the atrial junction of the cushion tissue and impaired gelatinase activities in the muscular component of the interventricular septum at embryonic day 12.5, when fusion between the endocardial cushion tissue and the atrial and ventricular septa occurs, indicating that these defects may underlie the observed AVSD. Moreover, human CCN1 maps to 1p21-p31, the chromosomal location of an AVSD susceptibility gene. Together, these results provide evidence that deficiency in matrix signaling can lead to autosomal dominant AVSD, identify Ccn1 +/− mice as a genetic model for ostium primum ASD, and implicate CCN1 as a candidate gene for AVSD in humans.
Impact of Overall Treatment Time on Survival and Local Control in Patients With Anal Cancer: A Pooled Data Analysis of Radiation Therapy Oncology Group Trials 87-04 and 98-11
Authors: Edgar Ben-Josef, Jennifer Moughan, Jaffer A. Ajani, Marshall Flam, Leonard Gunderson, JonDavid Pollock, Robert Myerson, Rani Anne, Seth A. Rosenthal, Christopher Willett
Journal: Journal of Clinical Oncology (2010)

Purpose To determine whether increased duration of radiation therapy (RT) and overall treatment (RX) time has a detrimental effect in anal cancer. Patients and Methods Data from Radiation Therapy Oncology Group (RTOG) 87-04 and RTOG 98-11 trials were combined to form three treatment groups: RT/fluorouracil (FU)/mitomycin (n = 472), RT/FU/cisplatin (n = 320), and RT/FU (n = 145). Cox proportional hazards models were used with the following variables: RT duration, RT intensity, RX duration, treatment group, age, sex, Karnofsky performance score (KPS), T stage, N stage, and RT dose. Results In the univariate analysis, there was a significant association between RX duration and colostomy failure (CF; hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.14; P = .02), local failure (HR = 1.52; 95% CI, 1.14 to 2.03; P = .005), locoregional failure (HR = 1.51; 95% CI, 1.15 to 1.98; P = .003), and time to failure (HR = 1.40; 95% CI, 1.10 to 1.79; P = .007). The significance of RX duration was maintained after adjusting for treatment group. In multivariate modeling there was a trend toward an association between RX duration and CF (HR = 1.57; 95% CI, 0.98 to 2.50; P = .06) and a statistically significant association with local failure (HR = 1.96; 95% CI, 1.34 to 2.87; P = .0006). Age, sex, KPS, T stage, N stage, and RT dose, but not RT duration, RT intensity, or RX duration, were found to be statistically significant predictors of OS and colostomy-free survival. Conclusion Total treatment time, but not duration of radiation therapy, seems to have a detrimental effect on local failure and colostomy rate in anal cancer. Induction chemotherapy may contribute to local failure by increasing total treatment time.
Sixty Years of <i>Pharmacological Reviews</i>: Has The Role of Review Articles in Biomedical Sciences Changed and, If So, How Does This Affect <i>Pharmacological Reviews</i>?
Authors: Eric P Brass, Ross D Feldman
Journal: Pharmacological Reviews (2009)

Pharmacological Reviews has been publishing high-quality review articles since 1949. Over those 60, years the pharmacological sciences have changed dramatically; accompanying this change in the science has been the development and use of information technologies. These changes have undoubtedly led
Relationship between the clinical response to adalimumab treatment and serum levels of adalimumab and anti-adalimumab antibodies in patients with psoriatic arthritis
Authors: A W R van Kuijk, M de Groot, S O Stapel, B A C Dijkmans, G J Wolbink, P P Tak
Journal: Annals of the Rheumatic Diseases (2010)

While the majority of patients with psoriatic arthritis (PsA) respond well to treatment with adalimumab, some patients lose response.1 An explanation might be the development of antiadalimumab antibodies, which has been reported in rheumatoid arthritis.2 3 Therefore, we studied the incidence of antiadalimumab antibodies in PsA, and the relationship with serum adalimumab concentration and clinical response.

Twenty-two patients with active PsA, fulfilling CASPAR classification criteria,4 started adalimumab treatment (table 1). The patients met the requirements of the Dutch consensus on initiation of tumour necrosis factor blocking therapy in PsA5 and were seen at baseline, and after 3 and 12 months. Serum samples were collected just before the next injection with adalimumab. The Disease Activity Score in 28 joints (DAS28), which has been shown to discriminate between active drug and placebo in clinical trials in …
Physical performance of patients with numerous psychosomatic complaints suggestive of hyperventilation
Authors: T Troosters, A Verstraete, K Ramon, R Schepers, R Gosselink, M Decramer, KP Van de Woestijne
Journal: European Respiratory Journal (1999)

In some patients exercise induces numerous complaints which cannot be attributed to an organic disorder, and which are suggestive of hyperventilation. The study was designed to investigate in this type of patient: 1) exercise capacity and muscle force; 2) breathing pattern and symptoms during maximal exercise and recovery; 3) relationships between symptoms and breathing pattern. Twenty-four patients were compared with 20 healthy subjects. They performed a maximal incremental cycle ergometer test and peripheral and respiratory muscle strength were measured. Patients tended to have a decreased exercise capacity and presented with moderately reduced muscle strength. At comparable minute ventilation, breathing frequency was higher (mean: 24 versus 21 per minute) and tidal volume smaller (mean: 1.42 versus 1.67 L). End-tidal partial pressure of carbon dioxide (PET,CO2) was not significantly different. A significant relation was observed between PET,CO2 and respiratory frequency during recovery in patients, suggesting a reduced flexibility of the ventilatory response to exercise. In patients respiratory complaints and paresthesias were weakly correlated to PET,CO2 at moderate exercise. It is suggested that the physical deconditioning observed in those patients is rather a consequence than a cause of the response to exercise. The link between symptoms and breathing pattern might be explained by a psychological conditioning process.
Effect of Atrial Fibrillation on Hematopoietic Progenitor Cells
Authors: Andreas Goette, Kathleen Jentsch-Ullrich, Uwe Lendeckel, Christoph Röcken, Mahmood Agbaria, Angelo Auricchio, Martin Mohren, Astrid Franke, Helmut U. Klein
Journal: Circulation (2003)

Background— Injury to the heart causes hematopoietic progenitor cells (HPCs) to migrate to the site of damage and to undergo cell differentiation. Studies suggest that myocardial progenitor cells invade atrial tissue. So far it is unclear, however, whether an atrial disease per se affects circulating HPCs. Methods and Results— Seventeen patients with persistent atrial fibrillation (persistAF), 12 with paroxysmal AF (paroxAF), and 17 matched patients with sinus rhythm (SR) were studied. HPCs (CD34 + and CD34 + /CD117 + ) were quantified with the use of a fluorescence-activated cell sorter; stromal cell–derived factor-1α (SDF-1α), vascular endothelium growth factor (VEGF), and atrial natriuretic peptide (ANP) were determined by immunoassays. In patients with persistAF, blood samples were obtained before as well as 10 minutes, 24 hours, and 48 hours after electrical cardioversion. CD34 + HPCs (AF, 7.0±2.3×103/mL versus SR, 5.0±1.6×10 3 /mL; P &lt;0.01) were increased during persistAF only. Highest SDF-1α levels were also observed during persistAF. Successful and unsuccessful cardioversion decreased CD34 + HPCs temporarily (7.0±2.3×10 3 /mL versus 24 hours: 5.0±1.5×10 3 /mL; P &lt;0.05). Forty-eight hours after successful cardioversion, SDF-1α and CD34 + HPC levels started to decline, reaching control levels after 59±19 days. CD34 + /CD117 + and VEGF levels, however, were increased by DC energy but not by AF. ANP levels correlated with CD34 + HPC ( r =0.76; P &lt;0.01) and SDF-1α ( r =0.56; P &lt;0.01). HPCs from patients with AF had a greater tendency to differentiate into cells expressing (cardio)myocyte markers ANP and myocyte enhancer factor-2. Conclusions— PersistAF appears to increase the potential of HPCs for (cardio)myogenesis. Restitution of CD34 + HPC levels, mediated by SDF-1α and possibly ANP, occurs within several weeks after successful cardioversion.