tbuckley/cabot-search huggingface dataset:
Time-response course after endoscopic lung volume reduction – Analysis of the VENT trial
Authors: Daniela Gompelmann, Ralf Eberhardt, Maren Schuhmann, Konstantina Kontogianni, Arschang Valipour, Felix J.F. Herth
Journal: European Respiratory Journal (2014)

Objective:  The VENT compared the safety and efficacy of Zephyr valve in heterogeneous emphysema to medical treatment. The time response course after the intervention, however, has not yet been addressed systematically.  Methods:  Patients were followed-up at 30, 90, 180 and 365 days after the intervention and the time of response, defined using validated minimal clinical important differences (MCIDs) of outcomes, was evaluated.  Results:  521 subjects were enrolled into the programme. An MCID of 12% were used for FEV1, -4 points for the SGRQ and a 6 MWT improvement of 26 m. The majority of the 1-year responders for SGRQ and 6MWT were responders within the first 90-days whereas the FEV1 had quite a few late (post 180-day) responders.  Conclusion:  The time-course of response to endoscopic lung volume reduction with the Zephyr valves varies according to selected outcomes, with quality of life and exercise capacity showing an early response compared with FEV1.
IMMUNOTHERAPY FOR GRASS POLLENOSIS WITH ALLPYRAL ALLERGEN EXTRACTS
Authors: H. MORROW BROWN, D. MCINTYRE
Journal: Allergy (1977)

Nasal provocation testing using a measured dose of dry grass pollen has been used as a method of controlling the amount of injection treatment required to achieve decreased sensitivity to grass pollen. This could seldom be shown at the usual top dose of 10,000 P.N.U., but by repeating the top dose until the reaction was negative, complete freedom from pollenosis was achieved in most cases. Strict criteria for assessment of results were used. Conventional dosage regimens produced only 27 percent excellent results, but 94 percent of those patients who became demonstrably nasal test-negative were completely or almost completely free from symptoms in the pollen season.
Systematic review: laparoscopic treatment of long-standing groin pain in athletes
Authors: Hannu Paajanen, Agneta Montgomery, Thomas Simon, Aali J Sheen
Journal: British Journal of Sports Medicine (2015)

Objectives No single aetiological factor has been proven to cause long-standing groin pain in athletes and no sole operative technique (either open or laparoscopic) has been shown to be the preferred method of repair. The aim of this systematic review was to determine whether there are any differences in the return to full sporting activity following laparoscopic repair of groin pain in athletes. Data sources The minimal access approaches include laparoscopic transabdominal pre-peritoneal (TAPP) or endoscopic total extraperitoneal (TEP) techniques. A systematic literature search was performed in PubMed, SCOPUS, UpToDate and the Cochrane Library databases. Series reporting laparoscopic repair (TAPP/TEP) of groin pain in adult (&gt;18 years) athletes were included. The primary outcome was return to full sporting activity and secondary outcomes included percentage success rates and complications of operations. Results Only 18 studies fulfilled the search criteria with both laparoscopic and sports hernia repairs. The studies were mainly observational with some reporting comparative data, but no large randomised controlled trials were detected. The median return to sporting activity of 4 weeks (28 days) was the same for the TAPP as well as TEP techniques. No real difference in secondary outcome measures was shown. More reported cases to date in the literature used the TAPP technique compared with TEP repair (n=605 vs n=266). Conclusions Laparoscopic surgery for elite athlete groin pain is increasingly becoming more common with almost 1000 patients reported since 1997. No particular laparoscopic technique appears to offer any advantage over the other.
Malignant pleural mesothelioma: a disease unaffected by current therapeutic maneuvers.
Authors: A S Alberts, G Falkson, L Goedhals, D A Vorobiof, C A Van der Merwe
Journal: Journal of Clinical Oncology (1988)

From 1965 to 1985, 262 patients with malignant pleural mesothelioma were treated with cytostatics only; radiotherapy (RT); RT and cytostatics; or decortication plus RT plus cytostatics. The median survival (MS) from diagnosis was 9.6 months. This was similar for all comparable treatment groups. In a univariate analysis, significant favorable prognostic factors were good performance status (PS), duration of symptoms greater than 6 months at the time of diagnosis, early stage of disease, white race, and female sex. In a multivariate analysis, PS, race, duration of symptoms, and stage were of significance for a favorable prognosis. Age, pain as first symptom, histologic subtype, and RT dose were not of prognosis significance in this study. The stepwise addition of treatment modalities did not increase survival, which remained the same as that reported for untreated patients. Therefore, phase II trials of new agents offer the only hope for advance in the treatment of this disease.
Swinging for the Fences: Long-Term Survival With Ipilimumab in Metastatic Melanoma
Authors: Geoffrey T. Gibney, Michael B. Atkins
Journal: Journal of Clinical Oncology (2015)

A 40-year-old man with stage III melanoma arising from his left shoulder underwent wide local excision, sentinel lymph node biopsy, and lymph node dissection. Nine months after receiving adjuvant biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2 (IL-2), and interferon alfa as part of a clinical trial, he developed headaches and right-hand weakness and was found to have a 2-cm left parietal CNS metastasis. A comprehensive staging workup identified multiple nonspecific subcentimeter pulmonary nodules. The brain mass was resected and confirmed to be metastatic melanoma; the surgical bed was treated with stereotactic radiosurgery. He was monitored off therapy, but 5 months later, he developed a second left parietal CNS metastasis and enlarging lung nodules. The new brain lesion was treated with stereotactic radiosurgery, and he began systemic therapy with ipilimumab on a clinical trial. After the third dose, he presented with headache, nausea, and vomiting; a brain magnetic resonance imaging scan showed left anterior temporal enhancement, possibly representing new disease. His symptoms improved with a course of corticosteroids. Restaging of the chest showed a mixed response among the pulmonary nodules. After tapering off corticosteroids, he received the fourth dose of ipilimumab, which was complicated by grade 3 transaminitis and hypophysitis with documented hypothyroidism and adrenal insufficiency. They were managed with corticosteroids and thyroid and adrenal hormone replacement. Restaging scans showed further disease regression except for new confluent enhancing nodules and edema in the left temporal lobe. Craniotomy and resection of this area showed only necrotic tissue with no viable melanoma cells. Nine years after treatment with ipilimumab, he is alive and shows no evidence of melanoma on the basis of annual computed tomography scans of the chest, abdomen, and pelvis and magnetic resonance imaging scans of the brain. He has full neurologic function but still requires hormone replacement for persistent hypopituitarism.
Inherited Methylmalonyl CoA Mutase Apoenzyme Deficiency in Human Fibroblasts
Authors: Huntington F. Willard, Leon E. Rosenberg
Journal: Journal of Clinical Investigation (1980)

We have measured and characterized methylmalonyl coenzyme A (CoA) mutase activity in extracts of cultured human fibroblasts from 23 patients with inherited deficiency of the mutase apoenzyme and from eight obligate heterozygotes for this defect. The mutant cell lines fall into two categories. Those without detectable residual mutase activity in cell extracts (>0.1% of control), and whose ability to utilize propionate in intact cells is refractory to supplementation of the culture medium with hydroxocobalamin, are designated mut degrees mutants. Those with detectable residual activity in cell extracts ( approximately 0.5-50% of control), and whose ability to utilize propionate in intact cells in markedly increased by hydroxocobalamin supplementation, are designated mut(-) mutants. The mutant enzyme in the mut(-) mutants exhibits a 50- to 5,000-fold elevated Michaelis constant (K(m)) for adenosylcobalamin in vitro, a normal K(m) for methylmalonyl CoA, and a strikingly reduced thermal stability at 45 degrees C relative to control. Mutase from one mut(-) mutant turns over at a rate three to four times that of control enzyme when cells are grown in hydroxocobalamin-supplemented medium.To detect heterozygous carriers of mutant mut alleles, we compared mutase activity in fibroblast extracts from four controls with that from eight parents of either mut degrees or mut(-) mutants. After cell growth in either unsupplemented or hydroxocobalamin-supplemented medium, activity in cell lines from heterozygotes was reduced to 47 or 37% of the mean control activities, respectively. We also examined the effect of adenosylcobalamin concentration on reaction kinetics of mutase from heterozygote cell lines. All four cell lines from parents of mut(-) mutants exhibited complex enzyme kinetics; approximately 80% of mutase activity demonstrated a K(m) indistinguishable from control, whereas a smaller component of activity exhibited a K(m) similar to the abnormal K(m) expressed by the mut(-) propositus in each family. In two families with a mut degrees propositus, mutase from three of the four parents exhibited only the normal K(m) for adenosylcobalamin, whereas mutase from one parent displayed complex kinetics, indicating expression of both a normal allele (mut(+)) and a mutant allele with an abnormal K(m). From these studies, we conclude that mut mutants reflect mutations at the autosomal gene locus for the methylmalonyl CoA mutase apoenzyme; that mut degrees , mut(-), and mut(+) alleles at this locus are codominantly expressed; and that some mut mutants may be genetic compounds, inheriting two different mut degrees or mut(-) alleles from their parents.
Improving utilization of patient portals through a multifaceted intervention strategy.
Authors: Patrick Higgins, Dawna Gillespie, Mary Coniglio, Carmen Guerra
Journal: Journal of Clinical Oncology (2013)

205 Background: Healthcare’s paradigm shift is in full swing. Electronic medical record (EMR) systems are up and running across the country, creating the potential for a more interactive environment for patients. With Stage 2 of the Affordable Care Act’s Meaningful Use requirements approaching in 2014, health systems are being challenged to determine how to effectively engage with patients electronically. MyPennMedicine is the portal used at the Abramson Cancer Center, and its use has been incredibly low since its introduction in 2009. Methods: Our assessment focused on patient portal account activations, messaging volume, and follow-through. Baseline measurements of these variables were abysmal. We convened an inter-disciplinary team of stakeholders (including patients, physicians, nurses, IT, front desk, and marketing) to understand current barriers to portal use, and to develop innovative methods aimed at improving use of the tool. Our team cultivated a strategy that included system upgrades based on end-user feedback, provider education about the benefits of the portal, patient demonstrations, and improving the ease of patient sign-ups. Results: At baseline (February, 2013), we determined that only 13% (18/139) of patients who had been assigned a code to access the patient portal actually did so. Our response to patient requests via the portal was only 58% (216/374). Moreover, the average time it took providers and staff to complete patient requests was 17.1 hours. After our first round of interventions (May, 2013), the rate of account activation increased to 45% (110/244) and our response to patient requests increased to 73% (331/455). The average time to complete the requests actually increased to 21.3 hours perhaps as a result of the increased volume. Conclusions: EMRs will continue to change the way we engage with patients. The clinical significance of our increase in patient portal usage is yet to be fully appreciated. Our initial interventions have resulted in significant increases patient awareness and utilization as well as improved follow-through by clinicians and staff. Future directions include additional interventions focused on technological improvements and continued education and clinician support.
Abstract 6189: Stent Fracture does not Affect Long Term Patency in the Femoro-popliteal Artery: Four Years Experience
Authors: Osamu Iida, Shinsuke Nanto, Masaaki Uematsu, Takakazu Morozumi, Tetsuya Watanabe, Masaki Awata, Toshinari Onishi, Fusako Sera, Hitoshi Minamiguchi, Masamichi Yano, Kuniyasu Ikeoka, Shin Okamoto, Nobuaki Tanaka, Haruyo Yasui, Takayuki ishihara, Tomoharu Dohi, Seiki Nagata
Journal: Circulation (2008)

[Background] Stent fracture in the femoro-popiteal (FP) artery has been related to poor long term patency. However, time course of patency with and without stent fracture beyond 2 years has not been explored. [Methods] We studied consecutive 334 FP lesions that received provisional stenting with metallic or nitinol stents (Luminexx, Bard: 90 lesions and Smart, Cordis: 243 lesions). Stent fracture was determined by X-ray with multiple projections. Patency was either assessed by Duplex ultrasonography as peak systolic velocity ratio &gt; 2.5 or by angiography (% diameter stenosis &gt; 50%). [Results] Stent fracture occurred in 19% (55/334) lesions and restenosis rate at mean follow up (16+/−12 months) was 20% (67/334). Primary patency with or without stent fracture was 83% with fracture versus 68% without fracture at 1 year, p=0.03; 75% versus 60% at 2 years, p=0.04; 68% versus. 60% at 3 years, p=0.05; 63% versus 60% at 4 years, p=0.06. [Conclusion] Stent fracture affected the patency during the first 2 years, but unlikely affected the patency beyond 4 years.
Social and productive activities in elderly people
Authors: C. Riddoch
Journal: BMJ (2000)

Acute otitis media Norwegian consensus is that only children with recurrent episodes of otitis media need antibioticsEditor-O'Neill's review of the management of acute otitis media from Clinical Evidence was interesting. 1 Straand et al showed that 64% of children aged 0-12 years with acute otitis media in a Norwegian county received antibiotic treatment, 2 but in a study from an accident and emergency department in Tromsø 91% of the children with acute otitis media received antibiotics. 3 This shows the conflict between day to day practice and clinical guidelines that recommend no standard antibiotic treatment for acute otitis media.O'Neill also addresses the question whether children with recurrent otitis media benefit from antibiotic treatment.The latest Norwegian consensus recommends identifying children who should have antibiotic treatment every time they have otitis media. 4 These children have had three or more episodes of acute otitis media during the previous six months or four or more episodes during the previous year.Before the age of 2 years 40% of all children will have an episode of acute otitis media, and 4% will have recurrent episodes.Several studies have been performed to explain why these children are prone to ear infections.Risk factors include a genetic disposition, the age of the first ear infection, and male sex. 4 Concentrations of antibody against pneumococcus capsule antigens 6A, 14, and 19F are low, and children with recurrent infections are hypothesised to have delayed production of specific immunoglobulins, being unable to increase their own production until the age of 6. 4 These factors are reasons for giving children with recurrent episodes antibiotic prophylaxis as an alternative to surgical treatment.In a meta-analysis of 958 children one in nine showed improvement after antibiotic treatment. 1 In a small Swedish study intermittent antibiotic treatment with penicillin V for 10 days was given every time the child had an upper respiratory infection. 5 This resulted in a 50% reduction in acute otitis media in the group that received antibiotic prophylaxis.This shows why finding children with recurrent episodes of acute otitis media is an important issue in general practice.Studies are needed to identify how substantial the benefit from antibiotics is in this particular group.The most important issue, however, is to reduce the overuse of antibiotics in the children who will not have recurrent episodes and will therefore recover just as well without antibiotics.
Assessment of ATP degradation in bronchoalveolar lavage fluid
Authors: Zsofia Lazar, Marisa Braun, Anja Meyer, Jessica Beckert, Ildiko Horvath, Marco Idzko
Journal: European Respiratory Journal (2013)

Introduction: Extracellular adenosine triphosphate (ATP) via purinergic signalling plays a role in the development of airway inflammation. Elevated ATP concentration in airway samples was reported in inflammatory diseases. Airway ATP level is under tight control by enzymatic degradation, which could also affect ATP concentration measured in ex vivo biological samples.  Aim: To assess ATP degradation in bronchoalveolar lavage (BAL) fluid.  Methods: ATP was measured in BAL collected from 20 subjects (6 patients with interstitial lung diseases, 4 with asthma, 2 with COPD, 1-1 with extrinsic allergic alveolitis / Wegener granulomatosis / microaspiration / pleuritis / pulmonary hypertension / pneumonia and 2 healthy controls) within an hour after collection using luminometry. ATP degradation was assessed as the recovery of 1 μM ATP after 30 minutes. Seven samples were also collected on chelating solutions (0.32% sodium citrate or 2 mM EDTA+2 mM EGTA). Data were analyzed with non-parametric tests (median /interquartile range/).  Results: BAL fluid ATP concentration was 18 nM /4-107 nM/, and recovery of added ATP was 36% /29-82%/. ATP concentration was higher in samples treated with citrate (530 nM /375-715 nM/) or EDTA+EGTA (420 nM /234-828 nM/) compared to untreated samples (186 nM /39-302 nM/; p  Conclusion: Extracellular ATP is degraded at a variable speed in BAL fluid, which is effectively inhibited by chelating agents. The analysis of pre-treated BAL fluid might more precisely reflect airway ATP concentration.
Changes of IL-6 level in bronchoalveolar fluid in patients with acute exacerbation of COPD before and after the treatment with tiotropium bromide, and its significance
Authors: Mariana Kulynych-Miskiv, Mykola Ostrovskyy, Oleksandr Varunkiv, Iryna Savelikhina
Journal: European Respiratory Journal (2013)

Objective: To investigate the changes and significance of IL-6 level in bronchoalveolar fluid in patients with acute exacerbation of COPD before and after the treatment with tiotropium bromide.  Methods: The IL-6 level in bronchoalveolar fluid of 45 COPD patients with acute exacerbation and 15 healthy people (control) were determined by using double-antibody sandwich enzyme-linked immunosorbent assay.  Results: The IL-6 level in bronchoalveolar fluid of COPD group before the treatment were significantly higher than those after the treatment with tiotropium bromide, and both were higher than those of control group.  Conclusions: IL-6 contributes to the development of COPD and its continuous high level may be one of the important factors resulting in chronic airway inflammation.
Endothelin-1 induced connective tissue growth factor expression in human lung fibroblasts by ETAR-dependent JNK/AP-1 pathway
Authors: Chien-Huang Lin, Chih-Ming Weng, Bing-Chang Chen, Min-Liang Kuo
Journal: European Respiratory Journal (2013)

Endothelin-1 (ET-1) acts as a key mediator of vasoconstriction and tissue repair. Overproduction of connective tissue growth factor (CTGF) underlies the development of lung fibrosis. However, little is known about the signaling pathway of CTGF expression caused by ET-1. We investigated the effect of ET-1 in CTGF expression in human lung fibroblasts by western blot, reporter gene assay and chromatin immunoprecipitation assay, etc. ET-1 caused concentration- and time-dependently increases in CTGF expression in primary normal adult human lung fibroblasts and human lung fibroblasts (WI-38). ET-1-induced CTGF expression was inhibited by BQ123 (ETAR antagonist), but not BQ788 (ETBR antagonist). Moreover, ET-1-induced CTGF expression was reduced by JNK inhibitor (SP600125), the dominant-negative mutants of JNK1/2 (JNK1/2 DN), and AP-1 inhibitor (curcumin). ET-1 induced phosphorylations of JNK and c-Jun in time-dependent manners. ET-1 induced the increase of AP-1 luciferase activity, and this effect was attenuated by SP600125. ET-1-indiced CTGF luciferase activity was predominately controlled by the sequence -747 to -408 bp upstream of the transcription start site on the human CTGF promoter. Furthermore, ET-1 caused the formation of AP-1-specific DNA-protein complex and the recruitment of c-Jun to the CTGF promoter. Moreover, we found that ET-1 induced α-smooth muscle actin (α-SMA) expression, which was inhibited by BQ123, SP600125, curcumin, and anti-CTGF antibody. These results suggest that ET-1 stimulates expressions of CTGF and α-SMA through ETAR/JNK/AP-1 signaling pathway, and CTGF is required for ET-1-induced α-SMA expression in human lung fibroblasts.
Role of low molecular weight heparin (LMWH) in central venous catheter antithrombotic prophylaxis
Authors: D. Tassinari, E. Scarpi, S. Rupoli, P. Leoni
Journal: Journal of Clinical Oncology (2007)

9010 Background: To assess the role of LMWH in antithrombotic prophylaxis in cancer patients with a central venous catheter. Methods: A systematic review of literature in the MEDLINE and EMBASE data bases from 1966 to October 2006, using “anticoagulants/*administration &amp; dosage” [MeSH term], “cancer patient” [MeSH term], “catheterization, central venous/*adverse effect” [MeSH term], “catheters, indwelling/adverse effects” “central venous catheter” [MeSH term], “dalteparin/*administration and dosage” [MeSH term], “enoxaparin/*administration and dosage” [MeSH term], “low molecular weight heparin/*administration and dosage” [MeSH term], “nadroparin/*administration and dosage” [MeSH term], “neoplasm/drug therapy” [MeSH term], “reviparin/*administration and dosage” [MeSH term], “venous thrombosis/*etiology/*prevention &amp; control/radiography” [MeSH term], a search was performed independently by two authors (DT and ES). All the randomized phase III trials comparing LMWH and placebo were considered eligible and included into the analysis. The risk reduction (RR) of upper limb venous thrombosis (ULVT) was the primary outcome of the analysis. Heterogeneity between the trials was analysed using the Mantel-Haenszel test, and the outcome analysis was performed using a random effects model and an alpha error lower than 5%. Results: 5 trials met the selection criteria and were included into the analysis. The outcome of 1,367 patients (793 treated with LMWE and 574 treated with placebo) was compared in the pooled analysis. A significant heterogeneity was documented between the trials (p=0.005), while no heterogeneity was observed when a trial with a low quality in the presented data was excluded from the analysis (p=0.777). No significant differences in RR were observed both when all the trials were included into the analysis (RR=−2.4%, p=0.456) and when we excluded a trial for the low quality of presented data (RR=0.2%, p=0.896). Conclusion: Antithrombotic prophylaxis with LMWH does not reduce the risk of ULVT in oncologic patients with central venous catheter, and its routine use seems to be not-recommended in clinical practice. No significant financial relationships to disclose.