tbuckley/cabot-search huggingface dataset:
Ewing's sarcoma of soft tissues in childhood: a report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991.
Authors: R B Raney, L Asmar, W A Newton, C Bagwell, J C Breneman, W Crist, E A Gehan, B Webber, M Wharam, E S Wiener, J R Anderson, H M Maurer
Journal: Journal of Clinical Oncology (1997)

PURPOSE One hundred thirty of 2,792 patients (5%) registered on three Intergroup Rhabdomyosarcoma Study clinical trials (IRS-I, -II, and -III) from 1972 to 1991 had an extraosseous Ewing's sarcoma (EOE). We report here the results of multimodality therapy for this tumor. PATIENTS AND METHODS The 130 patients were less than 21 years of age; 70 (54%) were males. Primary tumor sites were on the trunk in 41 patients, an extremity in 34, the head/neck in 23, the retroperitoneum/pelvis in 21, and other sites in 11. One hundred fourteen patients had no metastases at diagnosis. In 21 patients, the tumor was completely resected; in 30, the localized or regional tumor was grossly resected, and in 63 patients, grossly visible sarcoma was left behind. Sixteen patients (12%) had distant metastases at diagnosis. All patients were given multiagent chemotherapy and most received irradiation (XRT); none were treated with bone marrow transplantation. RESULTS One hundred seven patients (82%) achieved a complete response. At 10 years, 62%, 61%, and 77% of the patients were alive after treatment on IRS-I, IRS-II, or IRS-III therapeutic protocols, respectively, similar to figures obtained in all IRS patients. At last follow-up evaluation, 42 patients had died of progressive tumor and one of infection. Survival at 10 years was most likely for patients with tumor that arose in the head and neck, extremities, and trunk, and for those who underwent grossly complete tumor removal before initiation of chemotherapy. For patients with localized, gross residual tumor, adding doxorubicin (DOX) to the combination of vincristine, dactinomycin, cyclophosphamide (VAC), and XRT did not significantly improve survival in 39 patients (62% alive at 10 years) compared with that of 24 patients treated with VAC and XRT without DOX (65% alive at 10 years, P = .93). CONCLUSION This series indicated that EOE in children is similar to rhabdomyosarcoma (RMS) in its response to multimodal treatment. No benefit was apparent from the addition of DOX to VAC chemotherapy in patients with gross residual EOE.
Alpha-1 antitrypsin ameliorates inhibition of wound repair by neutrophil elastase
Authors: Luke Garratt, Erika Sutanto, Kak-Ming Ling, Kevin Looi, Elizabeth Kicic-Starcevich, Thomas Iosifidis, Kelly Martinovich, Francis Lannigan, Stephen Stick, Anthony Kicic
Journal: European Respiratory Journal (2014)

Introduction: Cystic fibrosis (CF) is characterised by increasing free active neutrophil elastase (NE) that is significantly associated with bronchiectasis. Yet data on how NE affects function of primary epithelia in very young children is limited.

Aim: Do physiologically relevant, nanomolar (nM) concentrations of NE inhibit repair of airway epithelial cells (AEC) in a manner reversible by the antiprotease alpha 1-antitrypsin (A1AT).

Method: Non-CF (NuLi-1 & pAECNCF) and CF (CuFi-1 & pAECCF) AECs were used, with primary pAECNCF and pAECCF collected from paediatric airways (mean age 4.67 and 4.22 years respectively). Cells were exposed to 10-200 nM NE over 48-hours and viability, proliferative capacity, cytotoxicity and wound repair were assessed.

Results: Following exposure to 100 nM NE, pAECNCF and pAECCF viability (n = 4; 3.9% ±5.1, p<0.01 and 40.0% ±30.4, p<0.05) and proliferation (n = 4; 16.5% ±5.4, p<0.01 and 13.2% ±0.2, p<0.01) were significantly reduced compared to controls. Furthermore, 200 nM NE inhibited NuLi-1 and CuFi-1 scratch wound closure at 48 hours (n = 6; 32.01% of control, p<0.01 and 17.75% of control, p<0.01) and 50 nM NE inhibited pAECCF repair at 24 hours (n = 2; 69.99% of control, p<0.01). Addition of 1 µM A1AT at 12-hours post-wounding significantly reduced inhibition by NE at all concentrations assessed.

Conclusion: Biologically relevant concentrations of NE are associated with cytotoxicity, reduced proliferation and deficient wound repair providing a mechanism for bronchiectasis formation. Current anti-inflammation therapies may not be sufficient to reduce the impact of excess proteases in the CF airway and targeting protease activity offers an attractive therapeutic option.
Fiberoptic bronchoscopy assisted percuteneous dilatational trecheostomy: How safe is for an intensivist to perform it?
Authors: Kyriaki Tsikritsaki, Georgios Koukoulitsios, Christos Tsakalakis, Panagiotis Zotos, Nikodimos Katsarelis, Paraskevi Spyrou, Konstantinos Tsironas, Michalis Pedonomos
Journal: European Respiratory Journal (2011)

Background:  Intensive care unit (ICU) patients, mainly those who need prolonged ventilator support, may require trecheostomy, which once was done in the operating room. Percuteneous dilatational trecheostomy (PDT) was first described in 1985 and now is a well-established procedure that can be performed at the bedside by an intensivist with less surgical equipment required.   Aim:  To evaluate the safety of performing percuteneous dilatational trecheostomy (PDT) with Fiberoptic bronchoscopy assistance in patients requiring prolonged mechanical ventilation.   Material and method:  Sixty three patients 17-78yrs of age, 28 females and 35 males underwent PDT due to prolonged endotracheal intubation between December 2009 and January 2011. The procedures of percuteneous dilatation trecheostomy with guide wire dilator forceps (GWDF) were done bedside with bronchoscopic guidance under general anaesthesia in the ICU department. Operative and post operative complications were observed.   Results:  Overall complication rate was low and occurred in 5 patients (7, 9%), there was no procedure-related mortality. Subcutaneous emphysema without pneumothorax occurred in one patient, one patient had a transitory hypotension related to sedation and three patients had peristomal oozing.  The mean time for completion of the procedure was 15 minutes and no patient required conversion to surgical trecheostomy. The bronchoscopic examination that was performed in 38 of the patient 20 days after trecheostomy tube removal showed no scar formation.   Conclusion:  PDT with bronchoscopic guidance is a safe and easy procedure that can be done by an intensivist at the bedside setting.
Activity and tolerance of bosutinib in patients with AP and BP CML and Ph+ ALL
Authors: C. Gambacorti-Passerini, H. M. Kantarjian, M. Baccarani, K. Porkka, A. Turkina, A. Y. Zaritskey, S. Agarwal, B. Hewes, H. J. Khoury
Journal: Journal of Clinical Oncology (2008)

7049 Background: Bosutinib (SKI-606) is an orally available, src/Abl kinase inhibitor with minimal activity against PDGFR and c-Kit. An open-label study in pts with Ph+ AP (Accelerated Phase) or BP (Blast Phase) CML and ALL (Acute Lymphoblastic Leukemia) who failed prior imatinib ± other TKI therapy, is currently ongoing. Methods: Pts with resistance or intolerance to imatinib (± other tyrosine kinase inhibitors) received 500 mg daily of bosutinib. Results: Data for 72 pts (32 AP CML, 23 BP CML and 17 Ph+ ALL) is reported. With a median follow-up of 6.1 wks, 18% achieved CHR and with a follow-up of 7.6 wks, 22% achieved a major cytogenetic response. 27/53 (51%) evaluable pts had 13 different Bcr/Abl mutations including 5 pts with T315I. Complete hematologic response occurred in 1/3 (33%) pts with P-loop, 2/15 (13%) with non-P-loop, and in 5/18 (28%) pts with no mutation. MCyR occurred in 1/2 (50%) of pts with P-loop, 3/12 (18%) with non-P-loop, and in 4/10 (40%) with no mutation. Only patients harboring T315I were consistently resistant to bosutinib. The most common treatment emergent adverse events (TEAEs) were diarrhea (61%), nausea (43%) and vomiting (38%); usually grade 1/2, manageable, and resolved after 3–4 weeks. Grade 3–4 hematologic laboratory abnormalities included thrombocytopenia (71%), neutropenia (46%) and anemia (32%). Fluid retention was reported as grade 1/2 in 11/72 (15%) and grade 3/4 in only 3/72 (4%) patients (including 2 pleural effusions). Fluid retention was considered unrelated to treatment in all cases. Conclusion: Bosutinib is active in pts with AP CML and BP CML and Ph+ ALL. Bosutinib demonstrates a favorable toxicity profile, primarily consisting of mild gastrointestinal symptoms. Response Patients Exposed to Imatinib Only Patients Exposed to Imatinib and other TKIs Patients, n (%) Patients, n (%) AP BP+ ALL AP BP +ALL Hematologic Response Evaluable 8 13 9 14 Complete 4 (50) 2 (15) 1 (11) 1 (7) Major (Complete + No evidence of leukemia) 7 (88) 2 (15) 1 (11) 1 (7) Cytogenetic Response Evaluable 9 11 6 10 Complete 2 (22) 1 (9) 0 2 (20) Major (Complete + Partial) 4 (44) 2 (18) 0 2 (20) Molecular Response Evaluable 8 14 7 15 Major 0 5 (36) 0 0 No significant financial relationships to disclose.
Non-invasive continuous positive airway pressure versus oxygen venturi in severe acute respiratory failure due to pneumonia: A randomized controlled trial
Authors: Elena Prina, Anna Maria Brambilla, Stefano Aliberti, Federico Piffer, Viviana Bozzano, Benedetto Visintin, Andrea Cellini, Manuela Del Forno, Francesco Corradi, Giovanni Ferrari, Stefano Nava, Paolo Pelosi, Roberto Cosentini
Journal: European Respiratory Journal (2013)

Non-invasive continuous positive airway pressure (CPAP) has been proved to rapidly improve oxygenation in moderate hypoxemic acute respiratory failure (ARF) due to pneumonia. No prospective randomized studies evaluated the role of CPAP in improving outcomes of patients with pneumonia. The aim of the study was to compare CPAP vs.Venturi Mask oxygen therapy (VM) in terms of criteria for endotracheal intubation (ETI) during pneumonia. This was a multicenter, prospective, randomized, controlled trial enrolling patients with severe hypoxemic ARF due to pneumonia (defined as PaO2/FiO2 ratio≤250 in VM with FiO2≥0.5 and respiratory rate≥30 breaths/min or respiratory distress) admitted to four Italian emergency departments from Feb. 2010 to Jan. 2013. Patients were randomized to receive CPAP delivered by a helmet or oxygen delivered with a VM. Criteria for ETI included ≥1 of major criteria (respiratory arrest, respiratory pauses with unconsciousness, severe hemodynamic instability, need of sedation) or ≥2 of minor criteria maintained for at least 1 hour (reduction of ≥30% of basal PaO2/FiO2 ratio, increasing of 20% of PaCO2 if basal PaCO2 was≥40 mmHg, worsening of alertness, respiratory distress, SpO2  Non-invasive CPAP delivered by a helmet reduces the risk of meeting ETI criteria in comparison to oxygen therapy in patients with severe ARF due to pneumonia.
Protracted bacterial bronchitis and malacias: Which came first , the chicken or the egg?
Authors: Marcela Moreno, Silvia Castillo, Carolina Castaño, Marta Trujillo, Nora Sivó, Amparo Escribano
Journal: European Respiratory Journal (2014)

Aims : to determine the prevalence of airway malacias in children diagnosed with persistent bacterial bronchitis (PBB) and evaluate the influence of malacias on the development of PBB.   Methods:  review of all children diagnosed with PBB in the last 8 years [wet chronic cough, atelectasis, noisy breathing, g10 4  colony forming units per millilitre of bacteria in bronchoalveolar lavage (BAL)], and all children diagnosed with tracheo or/and bronchomalacia. We investigated, in the PBB group, the association with malacias and in the malacia group, those with PBB. Major diagnostic (cystic fibrosis, primary ciliary, dyskinesia and immunodeficiency) were excluded.   Results:  142 children with malacias, 121/142 tracheomalacias (56 moderate, 20 severe), 57/142 bronchomalacias and 36/142 tracheobronchomalacias. 53 children with PBB of which 40 had malacias (mainly moderate tracheomalacia) and only 10/53 BBP, have not malacias. 71% patients with malacias no had PBB at the moment of BAL. Average age of diagnosis of PBB was 3 years. The main indication for bronchoscopy was persistent cough.  Haemophilus influenzae,  Moraxella catarrhalis  and  Streptococcus pneumoniae  were the most prevalent microorganisms. 24/53 PBB had neutrophilia in BAL. Most PBB were treated with amoxicillin clavulanate during 15-21 days, 72% responded favorably. 80% of those with unfavorable evolution had moderate to severe tracheomalacia.   Conclusion : Patients PBB had high association with malacias, mainly moderate traqueomalacias, placing these functional abnormalities as a risk factor for persistent bronchial infection. This justify the empirical use of prolonged antibiotic treatment in patients with malacia and persistent bronchial symptoms.
What do we know about positive appraisals? Low cognitive cost, orbitofrontal-striatal connectivity, and only short-term bolstering of resilience
Authors: Jennifer S. Beer, Taru Flagan
Journal: Behavioral and Brain Sciences (2015)

Abstract The PASTOR framework needs to be reconciled with existing research on positive illusions, which finds that positive appraisals of stressors have a short shelf life as a mechanism of resilience, do not draw on costly executive functioning, and rely on neural networks that are distinct from those found in studies of experimentally instructed reappraisal or value.
Targeted empiric antibiotic therapy for children with non-oncological comorbidities and community-onset invasive bacterial infections
Authors: Rosy Wells, Kirsty Le Doare, Mike Sharland, Paul Heath, Shamez N. Ladhani, Adam Irwin, Laura Segal, Peter Riley, Sonia Navidnia, Gayle Appleby, Libby Calton, Anna-Louise Nichols, Jennifer Handforth, Helen Payne, Rim El Rifai, Rowan Heath, Sue Luck
Journal: Journal of Infection (2015)
Assessing the risk of future severe asthma exacerbations using CARAT questionnaire and lung function
Authors: Ana Pereira, Carla Martins, João Fonseca
Journal: European Respiratory Journal (2013)

Background:  We aimed to compare lung function (LF) and CARAT results between individuals with and without severe asthma exacerbations (S-Exa) during a 1 year follow-up and to estimate the risk of future S-Exa (FS-Exa) according to patient/LF characteristics and CARAT scores.  Methods : Retrospective cohort including adults with asthma and rhinitis (AR) that performed spirometry and completed CARAT in 2011 in an Allergy Department (n=397). S-Exa was defined as an episode of progressive increase in respiratory symptoms needing a burst of oral corticosteroid. Information on S-Exa was collected from clinical records considering a 12 month follow-up period (FS-Exa) and the 4 weeks previous to the evaluations (recent S-Exa). AR control was defined as CARAT total score (CARAT-T)≥24; lower airways/asthma (L) control as CARAT-L>15; upper airways (U) control as CARAT-U>8.  Results:  From 269 patients with complete information, 12%(31) had ≥1 FS-Exa. Individuals with FS-Exa, when compared with those without, were predominantly female (90 vs 70%; p=0.017), had higher BMI (28.9 vs26.8, p=0.035) and a higher prevalence of recent S-Exa (48 vs18%, p Conclusions : This study suggests that recent severe asthma exacerbations, %FEV1, BMI and asthma control assessed with CARAT may be used to predict future asthma exacerbations.
Identification of microRNAs specific for epithelial cell adhesion molecule–positive tumor cells in hepatocellular carcinoma
Authors: Junfang Ji, Xin Zheng, Marshonna Forgues, Taro Yamashita, Eliane L. Wauthier, Lola M. Reid, Xinyu Wen, Young Song, Jun S. Wei, Javed Khan, Snorri S. Thorgeirsson, Xin Wei Wang
Journal: Hepatology (2015)

Therapies that target cancer stem cells (CSCs) hold promise in eliminating cancer burden. However, normal stem cells are likely to be targeted owing to their similarities to CSCs. It is established that epithelial cell adhesion molecule (EpCAM) is a biomarker for normal hepatic stem cells (HpSCs), and EpCAM + AFP + hepatocellular carcinoma (HCC) cells have enriched hepatic CSCs. We sought to determine whether specific microRNAs (miRNAs) exist in hepatic CSCs that are not expressed in normal HpSCs. We performed a pair‐wise comparison of the miRNA transcriptome of EpCAM + and corresponding EpCAM − cells isolated from two primary HCC specimens, as well as from two fetal livers and three healthy adult liver donors by small RNA deep sequencing. We found that miR‐150, miR‐155, and miR‐223 were preferentially highly expressed in EpCAM + HCC cells, which was further validated. Their gene surrogates, identified using miRNA and messenger RNA profiling in a cohort of 292 HCC patients, were associated with patient prognosis. We further demonstrated that miR‐155 was highly expressed in EpCAM + HCC cells, compared to corresponding EpCAM − HCC cells, fetal livers with enriched normal hepatic progenitors, and normal adult livers with enriched mature hepatocytes. Suppressing miR‐155 resulted in a decreased EpCAM + fraction in HCC cells and reduced HCC cell colony formation, migration, and invasion in vitro . The reduced levels of identified miR‐155 targets predicted the shortened overall survival and time to recurrence of HCC patients. Conclusion : miR‐155 is highly elevated in EpCAM + HCC cells and might serve as a molecular target to eradicate the EpCAM + CSC population in human HCCs. (H epatology 2015;62:829–840)
Is hepatitis E virus an emerging problem in industrialized countries?
Authors: Ibrahim M. Sayed, Ann‐Sofie Vercouter, Sayed F. Abdelwahab, Koen Vercauteren, Philip Meuleman
Journal: Hepatology (2015)

Hepatitis E virus (HEV) is yearly responsible for approximately 20 million infections worldwide. Although most infections occur in developing countries, HEV appears to be an emerging problem in several industrialized countries, where it is mostly associated with either traveling to an HEV endemic area or contact with pigs, which represent a major reservoir of HEV. The major risk groups for HEV infection and its ensuing complications are elderly men, pregnant women, young children, immunocompromised patients, patients with preexisting liver disease, and workers that come into close contact with HEV-infected animals. Whereas HEV mainly causes acute self-limiting infections, chronic infections may occur among immunocompromised patients (e.g., transplant recipients and human immunodeficiency virus [HIV]-infected patients). Accordingly, HEV-HIV coinfection leads to accelerated liver cirrhosis and increased mortality rates compared to HEV infection alone, which is, except during pregnancy, usually associated with only low mortality. In the Western world, the most common genotype (gt) causing HEV infection is gt 3. Ribavirin (RBV) and interferon have been used successfully for treatment of HEV, but this treatment is contraindicated in certain patient groups. Therefore, novel antiviral compounds are highly needed, especially given that viral isolates with RBV resistance have been recently identified. Moreover, eradication of HEV is hampered by long-term environmental persistence of the virus, which represents a continuous source of the virus. In 2011, the first prophylactic HEV vaccine, Hecolin, was approved in China, but it is not yet globally available. In this review, we will discuss the molecular virology of HEV, mode of transmission in industrialized countries, and potential implications for different specific patient populations.
Response to Comment on Tay et al. A Very Low-Carbohydrate, Low–Saturated Fat Diet for Type 2 Diabetes Management: A Randomized Trial. Diabetes Care 2014;37:2909–2918
Authors: Jeannie Tay, Natalie D. Luscombe-Marsh, Campbell H. Thompson, Manny Noakes, Jonathan D. Buckley, Gary A. Wittert, William S. Yancy, Grant D. Brinkworth
Journal: Diabetes Care (2015)

Maiorino et al. (1) correctly identify that HbA1c was the primary outcome of our previously reported study (2) but may have misunderstood the statistical approach used to evaluate the diet effects on outcomes, including HbA1c, when they suggest a subgroup analysis was used as opposed to the whole-population analysis that was performed.

The primary objective of our study was to compare the effects of a very low-carbohydrate (LC) diet to a high–unrefined carbohydrate (HC) diet on glycemic control and cardiovascular disease risk factors in obese adults with type 2 diabetes. The study used a randomized groups, pretest-posttest design and the planned analysis of the …
Epidemiology of methicillin-susceptible Staphylococcus aureus lineages in five major African towns: high prevalence of Panton-Valentine leukocidin genes
Authors: S. Breurec, C. Fall, R. Pouillot, P. Boisier, S. Brisse, F. Diene-Sarr, S. Djibo, J. Etienne, M.C. Fonkoua, J.D. Perrier-Gros-Claude, C.E. Ramarokoto, F. Randrianirina, J.M. Thiberge, S.B. Zriouil, B. Garin, F. Laurent
Journal: Clinical Microbiology and Infection (2010)
A Review of the Symptomatic Management of Malignant Gliomas in Adults
Authors: Umang Shah, Tara Morrison
Journal: Journal of the National Comprehensive Cancer Network (2013)

Malignant brain tumors are aggressive tumors with a very poor prognosis. Survival is on average 12 to 18 months. Patients with malignant gliomas are subject to multiple medical problems that can significantly impact their overall survival and quality of life, including seizures, cerebral edema, venous thromboembolism, cognitive and psychiatric disorders, and side effects of chemotherapy, such as nausea, vomiting, myelosuppression, constipation, and diarrhea. This article examines the evidence for managing many of these issues to reduce symptoms and improve quality of life.
24/7 technology--who needs it?
Authors: C. Brizzell
Journal: BMJ (2015)

At the Conservative party spring conference David Cameron pledged that, if they formed a new government, the party “would substantially extend weekend working of NHS services.” Post-election, the question is how will it be possible to resource a fully functioning 24/7 NHS when we are struggling to afford the current system? Provision of care seven days a week will increase the demand on already stretched primary and secondary care services, and therefore we need to ask who exactly will be expected to provide it. 

In a research paper, Fiona Warren and colleagues analysed results of the GP …
Diffuse dendriform pulmonary ossification in a usual interstitial pneumonia-like distribution: A distinct entity or a variant of idiopathic pulmonary fibrosis?
Authors: Hans Slabbynck, Tom De Beukelaar, Filip Hoet, Didier De Surgeloose, Karina Charels, Jozef Van Goethem
Journal: European Respiratory Journal (2014)

Diffuse dendriform pulmonary ossificiation (DPO) is a rare disease characterized by diffuse small bone fragments in lung tissue. Diagnosis is revealed by a coral-like, branching, dendritic pattern of bone density on high resolution CT (HRCT) with osteoporosis window settings. Dendriform DPO is associated with chronic pulmonary disorders.  HRCT criteria for a definite usual interstitial pneumonia (UIP) pattern include a predominantly subpleural and basilar distribution of reticular pattern in the absence of inconsistent features and associated with honeycombing. A possible UIP pattern is identical with the omission of honeycombing.  There are only a handful of case reports of DPO with a UIP-like distribution diagnosed during life. In older autopsy series the prevalence of DPO features in IPF is as high as 9 %. In a recent study of 10426 autopsy cases, there were 5 cases of dendriform DPO with a UIP distribution. In a HRCT study, mild DPO was identified in 5 of 75 patients with UIP.  We report three elderly men in whom HRCT revealed the diagnosis of extensive dendriform DPO in a UIP-distribution. They were former smokers, one had exposure as a metal worker. In one patient autopsy subsequently confirmed the diagnosis of DPO. Two patients are brothers, suggesting a genetic predisposition.  The slowly progressive nature of the disorder contrasting with idiopathic pulmonary fibrosis (IPF), the absence of radiological honeycombing despite longlasting disease, and the highly likelihood of a genetic predisposition suggest that DPO in a UIP-like distribution is at least a variant phenotype of IPF or might be just a different entity.