tbuckley/cabot-search huggingface dataset:
The effect of pulmonary rehabilitation on non COPD patients
Authors: Ariel Rokach, Nissim Arish, Romem Ayal, Hava Azulai, Milca Bartish, Gabriel Izbicki
Journal: European Respiratory Journal (2014)

Introduction  : Pulmonary rehabilitation has demonstrated significant improvements among COPD patients. The effect on non COPD patients is less well established.    Aims and Objective:  We wanted to find out whether pulmonary rehabilitation is also beneficial in non COPD patients.    Methods:  We collected the data about one hundred and three non COPD patients that participated in pulmonary rehabilitation program in our hospital .  The program took place in hospital environment and was run according to the ERS/ATS guidelines on pulmonary rehabilitation. Six minute walk (6MW) test was performed at the beginning of the program and at the end. Saint George Respiratory Questioner (SGRQ) was also performed at the beginning and at the end.    Result:   We included One hundred and three non COPD patients participated in the program between 2009 to 2013. Seventy three patients with interstitial lung disease (ILD), 23 with Asthma and seven with pulmonary hypertension. All the patients demonstrated significant impressive improvement in 6MW test and in SGRQ.  The patients suffering from ILD demonstrated fifty four meters (18.2%) improvement in the 6MW test (P    Conclusions:  We conclude that pulmonary rehabilitation is effective in interstitial lung disease, asthma and pulmonary hypertension. We believe that pulmonary rehabilitation should be offered to the majority of patients suffering from chronic respiratory disease.
Once-daily QVA149 improves dyspnoea, lung function and reduces rescue medication use in symptomatic patients with COPD using LAMA as prior medication: The BLAZE study
Authors: Anthony D'Urzo, Donald A. Mahler, Petter Olsson, Hungta Chen, Robert Fogel, Donald Banerji
Journal: European Respiratory Journal (2014)

Introduction 

The BLAZE study reported the superiority of an approved dual bronchodilator, QVA149 (GOLD group B-D), in terms of improvement in self-administered computerised version of transitional dyspnoea index (SAC-TDI) total score and lung function vs placebo (PBO) and tiotropium (TIO) in patients (pts) with COPD.1 Here, we present improvements in dyspnoea, lung function, and rescue medication use in the subgroup of pts on prior LAMA therapy.

Methods 

In this blinded, double-dummy, 3-period crossover study, pts (with mMRC≥2) with moderate-to-severe COPD were randomised to once-daily QVA149 110/50µg, PBO or TIO 18µg.

Results 

Of the 247 pts randomised, 115 were on prior LAMA therapy. Of these 115 pts, a higher proportion of pts on QVA149 reported ≥1unit improvement in the SAC-TDI total score (36.5%) vs PBO (16.4%; odds ratio [OR] 3.71; p<0.001) and TIO (20.2%; OR 2.51; p=0.007). At Day 1 and Wk 6, QVA149 provided significant improvements in mean FEV1 at all assessed time-points and FEV1 AUC0–4h vs both PBO and TIO (table). QVA149 significantly reduced (p<0.001) mean daily rescue medication use (puffs/day) by 1.55 vs PBO and by 0.68 vs TIO.

View this table:

Least squares mean treatment difference values of FEV1 and FEV1 AUC0-4h (mL)





Conclusion 

In the subgroup of pts on prior LAMA therapy, QVA149 significantly improved SAC-TDI total score and lung function while also reducing rescue medication usage vs PBO and TIO.

Reference :

1. Mahler et al. Eur Respir J 2013 Oct 31 (in press).
Impact of adjuvant radiation on the patterns and rate of relapse in advanced-stage Hodgkin's disease treated with alternating chemotherapy combinations.
Authors: J Yahalom, J Ryu, D J Straus, J J Gaynor, J Myers, J Caravelli, B D Clarkson, Z Fuks
Journal: Journal of Clinical Oncology (1991)

The role of adjuvant radiation therapy (RT) in the management of advanced-stage Hodgkin's disease (HD) was analyzed in 222 patients who attained a complete remission (CR) with alternating chemotherapy combinations. Mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) or MOPP/ABV alternating with the lomustine, melphalan, and vindesine combination (MOPP/ABV/CAD) were similarly effective in inducing a CR in 222 of 270 (83%) patients. These patients were scheduled to receive consolidative RT to bulky disease or other critical sites of initial nodal involvement to a total dose of 2,000 cGy, with an optional additional boost of 1,000 cGy. However, only 125 (56%) patients received radiation to all initial nodal sites of disease. In 69 (31%) patients, only selected nodal sites were included in the radiation fields, and 28 (13%) did not receive any RT. Of the 222 CR patients, 42 (19%) relapsed during a median follow-up period of 6.5 years (range, 2 to 15 years). Of these, 26 (62%) patients relapsed exclusively in unirradiated nodal sites, six (14%) within irradiated sites, and 10 (24%) both within and outside irradiated fields. The actuarial 10-year relapse-free survival (RFS) and overall survival (OS) for patients receiving radiation to all initially involved nodal sites were 89% and 94%, respectively, compared with 68% and 71% (P less than .0001) for patients who had only partial or no RT. Cox proportional hazards regression analysis showed that RT to all sites of initial disease was the most significant independent covariate (P less than .005) affecting RFS and OS. These data demonstrate that residual microscopic disease is relatively frequent in patients with apparent CR after alternating combination chemotherapy, and that irradiation of all sites of initial nodal involvement decreases relapse and improves survival in advanced-stage HD.
Risk-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma: analysis from a multicenter study
Authors: Yong Yang, Yuan Zhu, Jian-Zhong Cao, Yu-Jing Zhang, Li-Ming Xu, Zhi-Yong Yuan, Jun-Xin Wu, Wei Wang, Tao Wu, Bing Lu, Su-Yu Zhu, Li-Ting Qian, Fu-Quan Zhang, Xiao-Rong Hou, Ye-Xiong Li
Journal: Blood (2015)
Stability of freeze-dried pH-responsive dextrin nanogels containing doxorubicin
Authors: Somkamol Manchun, Crispin R. Dass, Pornsak Sriamornsak
Journal: Asian Journal of Pharmaceutical Sciences (2015)

Induction of non-specific toxicities by doxorubicin (DOX) has restricted conventional DOX-based chemotherapy. pH-responsive dextrin nanogels (DNGs) have been fabricated in order to incorporate and deliver DOX to specific (targeted) sites. However, adequate stability studies of DOX-loaded DNGs are required for selection of storage conditions. The aim of this study was therefore to evaluate the accelerated (25 °C/60% RH) and long-term (5 °C) stability of DNGs prepared with formaldehyde (FDNGs) and glyoxal (GDNGs) as cross-linker by determining the change in their physicochemical properties. The mean diameter decreased with time during long-term storage. The drug content between freshly prepared (initial day) and after storage at 5 °C for 180 days of DOX-loaded FDNGs and DOX-loaded GDNGs was not significantly different (p > 0.05), but decreased after storage under the accelerated condition. The release of DOX from all DNGs was pH-dependent. However, DNGs kept under the accelerated condition showed higher amount of DOX release than those stored at 5 °C and the freshly prepared ones. The results indicate that the stability of DNGs could be improved by their storage at 5 °C.
Intestinal microbiota in metabolic diseases
Authors: Thomas Clavel, Charles Desmarchelier, Dirk Haller, Philippe Gérard, Sascha Rohn, Patricia Lepage, Hannelore Daniel
Journal: Gut Microbes (2014)

The trillions of bacterial cells that colonize the mammalian digestive tract influence both host physiology and the fate of dietary compounds. Gnotobionts and fecal transplantation have been instrumental in revealing the causal role of intestinal bacteria in energy homeostasis and metabolic dysfunctions such as type-2 diabetes. However, the exact contribution of gut bacterial metabolism to host energy balance is still unclear and knowledge about underlying molecular mechanisms is scant. We have previously characterized cecal bacterial community functions and host responses in diet-induced obese mice using omics approaches. Based on these studies, we here discuss issues on the relevance of mouse models, give evidence that the metabolism of cholesterol-derived compounds by gut bacteria is of particular importance in the context of metabolic disorders and that dominant species of the family Coriobacteriaceae are good models to study these functions.
Chronic pulmonary diseases and the epidemiology of invasive pneumococcal infection
Authors: Malin Inghammar, Gunnar Engström, Bengt Ljungberg, Claes-Göran Löfdahl, Arne Egesten
Journal: European Respiratory Journal (2012)

Chronic pulmonary disease is an established risk factors for acquiring invasive pneumococcal disease (IPD), but estimates have in most cases been based on studies with aggregated denominator data on co-morbidities and have not been large enough to allow detailed analyses on less prevalent pulmonary diseases. There have also been conflicting results whether or not an underlying pulmonary disease increases the risk of death from IPD.

We examined the association between COPD, asthma, pulmonary fibrosis, sarcoidosis and pneumoconiosis and IPD, and the impact of these diseases on mortality from IPD.

IPD cases ≥18 years of age, 1990-2007, were identified via computerized databases. The associations between IPD and prior pulmonary diseases were assessed using conditional logistic regression, comparing IPD cases to 10 control subjects randomly selected from the general population (matched for sex, year of birth and county of residence). Adjustments were made for other chronic diseases, educational level and socio-economic position. Information on these was obtained through record linkage with other national databases.

4,085 cases of IPD were identified. COPD was associated with increased risk of IPD, (adjusted OR [aOR]: 4.7 (95% CI 4.0-5.6), as well as asthma (aOR: 2.2 [95% CI: 1.6-2.8]) and pulmonary fibrosis (aOR: 5.3 [95% CI:2 .8-10.0), whereas sarcoidosis and pneumoconiosis were not independently associated with increased risk of IPD. In-hospital mortality and 28-days mortality was not increased for patients suffering from the pulmonary diseases studied.

Several but not all pulmonary diseases increase the risk of IPD although this seems not be a risk factor for increased case-fatality rate.
Clinicoradiological features of pulmonary tuberculosis associated with interstitial pneumonia
Authors: Kazumasa Ogawa, Atsushi Miyamoto, Yui Takahashi, Makiko Takeyasu, Sayaka Mochizuki, Shigeo Hanada, Hironori Uruga, Hisashi Takaya, Nasa Morokawa, Atsuko Kurosaki, Hideki Araoka, Akiko Yoneyama, Kazuma Kishi
Journal: European Respiratory Journal (2014)

Pulmonary tuberculosis (TB) occasionally develops in patients with interstitial pneumonia (IP); however, there are few reported cases of TB with IP. The aim of this study was to evaluate the clinicoradiological features of TB patients who had IP.     Of 238 patients who showed positive results for Mycobacterium tuberculosis in sputum or bronchoalveolar lavage fluid cultures at the Toranomon Hospital, Japan from April 2007 to March 2013, we included 14 TB patients with IP (12 men, 2 women; median age, 73 years). We reviewed medical charts, high-resolution computed tomography (HRCT) findings, and bacteriological results. All HRCT findings were reviewed by a thoracic radiologist and two pulmonologists.    Of these 14 patients, 8 had idiopathic IP and 4 received steroid therapy. The HRCT findings of TB were classified into 3 subtypes: typical, having centrilobular nodules or cavities (4 patients, 28.6%); atypical, showing consolidation adjacent to fibrotic or emphysematous lesions without nodules (8 patients, 57.1%); and unidentifiable, characterized by no apparent TB lesions owing to diffuse parenchymal infiltrate caused by acute IP exacerbations (2 patients, 14.3%). 8 patients were treated with isoniazid, rifampicin, and ethambutol, and 6, with isoniazid, rifampicin, ethambutol, and pyrazinamide; subsequently, 13 showed a negative sputum culture. Although 4 patients could not complete the TB treatment owing to worsening of their general status, no patient died.    It is often difficult to diagnose TB in patients with IP because of their atypical HRCT findings ; however, appropriate TB treatment leads to a favorable outcome.
Response to fluorouracil therapy in cancer patients: the role of tumoral dihydropyrimidine dehydrogenase activity.
Authors: M C Etienne, S Chéradame, J L Fischel, P Formento, O Dassonville, N Renée, M Schneider, A Thyss, F Demard, G Milano
Journal: Journal of Clinical Oncology (1995)

PURPOSE The aim of the present study was to analyze the role of thymidylate synthase (TS; main cellular target of fluorouracil [FU]) and dihydropyrimidine dehydrogenase (DPD; rate-limiting enzyme of FU catabolism) in tumoral biopsies with respect to FU responsiveness. PATIENTS AND METHODS This prospective study was conducted on 62 head and neck cancer patients (six stage II, 16 stage III, and 40 stage IV). All received first-line chemotherapy with biomodulated FU (5-day continuous infusion). Before treatment, a tumor biopsy and control biopsy (symmetrical nontumoral area) were obtained. Cytosolic TS and DPD activities were measured using radioenzymatic assays. RESULTS DPD activity was detectable in all samples, without a significant difference between tumoral (median, 60 pmol/min/mg protein; range, 13 to 193) and nontumoral samples (median, 68 pmol/min/mg protein; range, 12 to 150). Tumoral TS and tumoral DPD were not significantly influenced by tumor localization or tumor staging. Among 52 tumors assessable for clinical response, we observed 46% complete responses (CRs), 33% partial responses (PRs), and 21% no responses (NRs). No relationship was demonstrated between TS activity and response to FU therapy. The comparison of tumoral DPD between complete responders and partial or nonresponders showed a trend toward significance (P = .06). In an attempt to reduce variability, we analyzed the tumoral/nontumoral DPD activity ratio; complete responders exhibited a significantly lower normalized DPD than partial or nonresponding patients (median, 0.86, 1.18, and 1.42 for CR, PR, and NR, respectively; CR v PR plus NR, P = .03). CONCLUSION Although resistance to FU is multifactorial, the present clinical study suggests that FU catabolism in target cells is probably a determinant factor for FU responsiveness in cancer patients and justifies the clinical use of specific DPD inhibitors as FU biomodulators.
Dose-ranging study of recombinant human granulocyte-macrophage colony-stimulating factor in small-cell lung carcinoma.
Authors: J Hamm, J H Schiller, C Cuffie, M Oken, R I Fisher, F Shepherd, G Kaiser
Journal: Journal of Clinical Oncology (1994)

PURPOSE This randomized, multicenter, dose-finding study was undertaken to determine the dose of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) that can safely reduce neutropenia after cyclophosphamide, doxorubicin, and etoposide (CAVP-16) chemotherapy in patients with small-cell lung cancer (SCLC). Secondary clinical end points included incidence of infection, intravenous (IV) antimicrobial use, and chemotherapy delivered. PATIENTS AND METHODS A total of 290 newly diagnosed SCLC patients were to receive six cycles of standard CAVP-16 chemotherapy on days 1 to 3 of every 21 days alone or with rhGM-CSF at 5, 10, or 20 micrograms/kg, administered subcutaneously (SC) on days 4 to 13 of each cycle. RESULTS In cycle 1, median absolute neutrophil count (ANC) nadirs were twofold to threefold higher in patients who received rhGM-CSF, although all values were less than 500/microliters, and recovery from neutropenia was faster at all rhGM-CSF dosages versus observation (P &lt; or = .01). In cycle 2, 56% of all patients given rhGM-CSF received full chemotherapy dosages (87.5% to 112.5% of projected dose) versus 36% of observation patients. During days 5 to 21 of cycle 1, fewer patients who received 10 micrograms/kg of rhGM-CSF required antibiotics compared with observation patients (11% v 29%, P &lt; or = .01). Adverse events that occurred more frequently in rhGM-CSF-treated patients included injection-site reaction, edema, asthenia, paresthesia, diarrhea, myalgia, musculoskeletal pain, Pruritus, and rash (P &lt; or = .10). Fever occurred more frequently in the 10- and 20-micrograms/kg rhGM-CSF groups than in the observation groups. The incidence in the 5-microgram/kg group was comparable to that in observation patients. Patients who received rhGM-CSF had a higher incidence of thrombocytopenia. CONCLUSION rhGM-CSF at 5 to 10 micrograms/kg reduces chemotherapy-associated neutropenia and should be the dose range used in future studies.
Patients with fluctuant peak expiratory flow value in the absent category are insensitive to dyspnea and are at risk for severe asthma exacerbation
Authors: Kumiya Sugiyama, Hirokuni Hirata, Naoya Ikeda, Taichi Shiobara, Masamitsu Tatewaki, Fumiya Fukushima, Masafumi Arima, Yasutsugu Fukushima, Takeshi Fukuda
Journal: European Respiratory Journal (2011)

Exacerbation of asthma has a negative impact on quality of life and increases the risk of fatal asthma. One of the known risk factors of patients with a history of near-fatal asthma is experiencing mild asthmatic symptoms as opposed to airway obstruction. We set out to find patients carrying such a risk before they experience severe exacerbation of asthma.  To determine the character of such patients, we compared the background and asthma diaries (mean period, 274 days) of 53 asthma patients with their symptoms and peak expiratory flow value (PEF). According to the criteria of the Japanese Society of Allergology, symptoms were classified into 8 categories ranging in severity from absent to severe attack.  Average PEF was 75.2% (50.5–100) in absent, 64.5% (36.6–92.6) in wheeze, 57.3% (25.0–94.7) in mild attack and 43.6% (20.4–83.1) in moderate attack, and the personal best was 100%. Thus, differences in decreased PEF in cases with the same symptoms varied widely between patients. PEF in wheeze, mild and moderate attack did not correlate significantly with the duration of asthma, FEV1 or the proportion of personal best to standard PEF. These PEFs did not show a significant difference in the groups that were divided by regular treatment of asthma, but did show a significant negative correlation with the coefficient of variation of PEF when asthma was absent.  To reveal patients who are insensitive to dyspnea, the most important factor to consider is the coefficient of variation of PEF when asthma is absent. When we find such patients who exhibit fluctuant PEF, we have to intervene in their treatment, even when they claim to be stable.
Hepatocyte buds derived from progenitor cells repopulate regions of parenchymal extinction in human cirrhosis
Authors: Ashley E. Stueck, Ian R. Wanless
Journal: Hepatology (2015)

Repair of cirrhotic livers occurs, in part, by repopulation with hepatocytes through the stem/progenitor pathway. There remain many uncertainties regarding this pathway. Hepatocyte "buds" occurring in broad septa are hypothesized to be the anatomic manifestation of this pathway. Our purpose was to define a morphologic sequence of bud maturation to allow a quantitative measure of the importance of the stem/progenitor pathway in humans. Histologic sections from 37 liver resection specimens were stained with trichrome, epithelial cell adhesion molecule (EpCAM), K19, CD34, glutamine synthetase (GS), and Ki-67. Specimens were stratified by etiology (10 biliary, 22 nonbiliary, five controls) and stage. Buds were defined as clusters of hepatocytes within septa. Five levels of bud maturation (0-4) were defined by the progressive increase in hepatocyte progeny relative to cholangiocytes. Level 0 single-cell buds are K19(+) /GS(+) /EpCAM(+) /Heppar1(-) . In level 1, the progeny are morphologically hepatocytes (K19(-) /GS(+) /EpCAM(+) /Heppar1(+) ). In level 2-4 buds, hepatocytes increase and become progressively GS(-) and EpCAM(-) . Associated endothelium is CD34(+) in level 1-2 buds and becomes CD34(-) near hepatic veins in level 3-4 buds. Progeny of the bud sequence may represent up to 70% of hepatocytes (immaturity index of 70%). In biliary disease, bud number is reduced in association with duct loss and cholestatic destruction of nascent buds.The stem/progenitor pathway, manifested anatomically by the bud sequence, is a major mechanism for repopulation of cirrhotic livers. The bud sequence reveals some critical features of hepatic morphogenesis, including that 1) the majority of distal cholangiocytes have stem-like properties, and 2) availability of bile ducts and/or venous drainage are limiting factors for regeneration.
Habenular CB1 Receptors Control the Expression of Aversive Memories
Authors: Edgar Soria-Gómez, Arnau Busquets-Garcia, Fei Hu, Amine Mehidi, Astrid Cannich, Liza Roux, Ines Louit, Lucille Alonso, Theresa Wiesner, Francois Georges, Danièle Verrier, Peggy Vincent, Guillaume Ferreira, Minmin Luo, Giovanni Marsicano
Journal: Neuron (2015)
Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels
Authors: Fabrice Danjou, Magdalena Zoledziewska, Carlo Sidore, Maristella Steri, Fabio Busonero, Andrea Maschio, Antonella Mulas, Lucia Perseu, Susanna Barella, Eleonora Porcu, Giorgio Pistis, Maristella Pitzalis, Mauro Pala, Stephan Menzel, Sarah Metrustry, Timothy D Spector, Lidia Leoni, Andrea Angius, Manuela Uda, Paolo Moi, Swee Lay Thein, Renzo Galanello, Gonçalo R Abecasis, David Schlessinger, Serena Sanna, Francesco Cucca
Journal: Nature Genetics (2015)
Optimal combination therapy with tropisetron in 445 patients with incomplete control of chemotherapy-induced nausea and vomiting.
Authors: F Hulstaert, S Van Belle, H Bleiberg, J L Canon, M Dewitte, M Buyse, P De Keyser, K J Westelinck
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study evaluated tropisetron (Navoban; Sandoz Pharma, Basle, Switzerland)-based combination therapy in patients who had incomplete control of chemotherapy-induced nausea or vomiting when using tropisetron as a single antiemetic agent. PATIENTS AND METHODS One thousand seventy-two patients, who were scheduled to receive at least two identical cycles of emetogenic chemotherapy, were treated with 5 mg tropisetron once daily in their first chemotherapy course. A 2 x 2 x 2 factorial design was used to evaluate three additional treatments to the recommended 5 mg once daily (intravenously [i.v.] on day 1; orally on days 2 through 6) tropisetron regimen during course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of course 1. Four hundred forty-five patients were centrally randomized to receive, in addition, open-label dexamethasone (day 1, 0.2 mg/kg i.v.; days 2 through 6, 8 mg orally) and/or open-label alizapride (day 1, 100 mg i.v. and 4 x 50 mg orally; days 2 through 6, 4 x 50 mg orally) and/or double-blind tropisetron (ie, doubling the dose to 10 mg once daily) or corresponding placebo. RESULTS Complete response rates (no nausea and no vomiting) were 72% for day 1 and 48% for days 1 through 6 of course 1. During course 2, more complete responders were observed when dexamethasone was added, both for day 1 (76% v 66%, P = .020) and for days 1 through 6 (50% v 34%, P = .0004). A moderate increase in the complete response rate was seen with the addition of conventional-dose alizapride (day 1, 75% v 68%, P = .14; days 1 through 6: 47% v 37%, P = .041). Doubling the dose of tropisetron did not change the complete response rate. CONCLUSION The addition of dexamethasone significantly increases the complete response rate of both acute and delayed emesis in patients who have incomplete disease control with tropisetron alone.