tbuckley/cabot-search huggingface dataset:
Building the Palliative Care Evidence Base: Lessons From a Randomized Controlled Trial of Oxygen vs Room Air for Refractory Dyspnea
Authors: Thomas W. LeBlanc, Amy P. Abernethy
Journal: Journal of the National Comprehensive Cancer Network (2014)

Palliative care is increasingly seen as a standard component of high-quality comprehensive cancer care. However, several challenges remain to its widespread integration into clinical oncology practice, including workforce problems, reimbursement concerns, and a fledgling evidence base. This article discusses issues surrounding evidence base development in palliative cancer care, using the example of a recently published randomized controlled trial of oxygen versus room air. The Oxygen Trial randomized patients with refractory dyspnea and adequate Pao2 to oxygen or room air, administered via nasal cannula. Both groups experienced improvements in self-rated dyspnea scores, but no statistical differences were seen between intervention arms. These results suggest that supplementary oxygen is often unnecessary in the palliative setting, and that room air is similarly efficacious. This example highlights the importance and need for ongoing development of the evidence base in palliative medicine. The Palliative Care Research Cooperative (PCRC) is a novel National Institute of Nursing Research-funded research infrastructure that seeks to expand the palliative care evidence base. Its first multisite trial was recently completed, assessing the pragmatic question of whether statin medications can be safely discontinued in end-of-life settings. The PCRC will be a vehicle through which a high-quality evidence base will continue to expand and develop. Such ongoing research efforts are needed to inform and improve palliative care practice.
Tumour suppressor gene methylation and screening for lung cancer
Authors: R Stretton
Journal: Thorax (2006)

▴ Belinsky SA, Klinge DM, Dekker JD, et al . Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clin Cancer Res2005;11:6505–11

[OpenUrl][1][Abstract/FREE Full Text][2]



Bronchial carcinoma is the leading cause of cancer death and often presents at an advanced stage. This study explored the exciting possibility of developing a screening tool for lung cancer. It assessed the level of inhibitory methylation of specific tumour suppressor genes in three groups of women with different levels of lung cancer risk. Plasma and sputum samples were taken from 74 …

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High-Dose Therapy and Autologous Stem-Cell Support for Chemosensitive Transformed Low-Grade Follicular Non-Hodgkin’s Lymphoma: A Case-Matched Study From the European Bone Marrow Transplant Registry
Authors: C. D. Williams, C. N. Harrison, T. A. Lister, A. J. Norton, A. K. Blystad, B. Coiffier, G. Taghipour, N. Schmitz, A. H. Goldstone
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To assess the outcome of high-dose therapy with autologous stem-cell support in patients with histologic transformation of low-grade follicular non-Hodgkin’s lymphoma (NHL) and identify significant prognostic factors, as well as to compare survival of these patients with that of patients with matched low-grade and de novo high- or intermediate-grade NHL undergoing the same procedure. PATIENTS AND METHODS: Fifty patients with transformed low-grade NHL have been reported to the European Bone Marrow Transplant registry. Outcome from high-dose therapy and significant prognostic factors were analyzed. Their survival was also compared with that of 200 patients with matched low-grade NHL and 200 patients with matched de novo high- or intermediate-grade NHL by a case-matched analysis. RESULTS: The procedure-related death rate among the 50 transformed NHL patients was 18%. Overall survival (OS) and progression-free survival (PFS) rates were 51% and 30% at 5 years, respectively. Median PFS time was 13 months. Raised lactate dehydrogenase levels at transformation (P = .0031) was identified as the only adverse significant predictor of PFS on multivariate analysis. A subgroup of patients with residual chemosensitive disease who attained complete remission after high-dose therapy had the best outcome, with an OS at 5 years of 69%. A comparison with matched patients with low-grade disease and with de novo high- or intermediate-grade lymphoma showed no significant difference in OS (P = .939 and P = .438, respectively). CONCLUSION: Patients with chemosensitive transformed lymphoma should be seriously considered for high-dose therapy and autologous stem-cell support.
Rapid reversal of radiation-induced murine pneumonitis by treatment with the anti-CTGF monoclonal antibody FG-3019
Authors: Kenneth Lipson, Ute Wirkner, Mark Sternlicht, Todd Seeley, Sebastian Bickelhaupt, Peter Peschke, Peter Huber
Journal: European Respiratory Journal (2011)

Rationale:  Connective tissue growth factor (CTGF) is a matricellular protein that is a central mediator of tissue remodeling characteristic of fibrosis. CTGF expression is elevated in patients with IPF. CTGF is essential for sustained fibrosis, and can mediate multiple steps in the process of fibrosis. Therefore, inhibition of CTGF may be therapeutically beneficial to fibrosis patients.   Methods:  Lung injury was initiated with a single, full thorax irradiation and administration of FG-3019 began 16 weeks after irradiation, when a significant increase in lung density was detectable by computed tomography (CT). Gene expression and histological analysis was performed at 18 weeks after irradiation.   Results:  Lung density in placebo-treated mice increased between 12 weeks and 30 weeks after irradiation. Treatment with FG-3019 reversed the radiation-induced lung density increase, which progressively decreased during the 8 weeks of administration and remained constant for another 6 months. Gene expression analysis and histological examination showed considerable infiltration of mast cells and macrophages at 18 weeks after irradiation in placebo-treated animals, while two weeks of FG-3019 restored levels to that of unirradiated mice.   Conclusions:  FG-3019 reversed radiation-induced pneumonitis and lung remodeling very quickly after administration was initiated and produced a durable effect on lung density. Because these are key events in the process of fibrosis, the data suggest that inhibition of CTGF can disrupt fibrotic processes after they have begun and support continued clinical evaluation of FG-3019 for treatment of pulmonary fibrosis.
Phase I study of busulfan and cyclophosphamide in preparation for allogeneic marrow transplant for patients with multiple myeloma.
Authors: W I Bensinger, C D Buckner, R A Clift, F B Petersen, J A Bianco, J W Singer, F R Appelbaum, W Dalton, P Beatty, A Fefer
Journal: Journal of Clinical Oncology (1992)

PURPOSE To study the toxicity and potential efficacy of busulfan (BU) and cyclophosphamide (CY) as a conditioning regimen before allogeneic bone marrow transplantation (ABMT) in patients with multiple myeloma (MM). PATIENTS AND METHODS Twenty patients with MM underwent conditioning, which was followed by ABMT from 16 HLA-identical donors, three one-antigen-mismatched donors, and one HLA A, B, D-identical unrelated donor. Four levels of BU plus CY were evaluated. RESULTS Severe regimen-related toxicity occurred in two of five patients who received BU 16 mg/kg and CY 120 mg/kg, in none of the four patients who received BU 14 mg/kg and CY 120 mg/kg, in one of eight patients who received BU 14 mg/kg and CY 147 mg/kg, and in two of three patients who received BU 14 mg/kg and CY 174 mg/kg. Twelve of 15 (80%) assessable patients achieved a complete remission with the disappearance of M-protein and the return of normal marrow morphology. Ten patients died of complications related to the ABMT, and two patients died of progressive or relapsed MM. Overall, eight of 20 patients were alive; seven (35%) were in complete remission 190 to 1,271 days after ABMT. CONCLUSIONS The maximum-tolerable dose given in this setting was BU 14 mg/kg and CY 147 kg/mg. These results suggest that this regimen may have significant antimyeloma activity. Further phase II studies are warranted.
The effect of anti-IL-33 antibody and soluble ST2 in a murine model of allergic asthma
Authors: Sook Young Lee, Hea Yon Lee, Chinkook Rhee
Journal: European Respiratory Journal (2013)

Background : Interleukin (IL)-33 is involved in development of allergic inflammation, and soluble ST2 (sST2) is a fusion protein that neutralizes IL-33 activity. Therefore, we aimed to investigate whether Anti-IL-33 and sST2 reduced inflammation in asthma.   Methods:  Fourty BALB/c mice were used. In group A (control group, n = 6), mice were sensitized and challenged with saline. Group B [ovalbumin (OVA) group, n = 6] mice received subcutaneous and intranasal OVA challenge. In group C (control goat IgG group, n = 6), mice were injected intraperitoneally with control IgG before OVA challenge. In group D (anti-IL-33 group, n = 8), anti-IL-33 was injected intraperitoneally before OVA challenge. In group E (control human IgG group, n = 6), mice were injected intraperitoneally with control IgG before OVA challenge. In group F (sST2 group, n = 8), sST2 was injected intraperitoneally before challenge. We evaluated the number of eosinophils, neutrophils, lymphocytes and macrophages in bronchoalveolar lavage (BAL) fluid; airway hyperresponsiveness (AHR) to methacholine; and IL-4, IL-5, IL-10 and IL-13 in BAL fluid.   Results:  Anti-IL-33 treatment significantly reduced the number of eosinophils in BAL fluid. IL-4, IL-5, IL-10, and IL-13 in BAL fluid were also significantly decreased after Anti-IL-33 treatment. sST2 also significantly reduced the number of eosinophils in BAL fluid. IL-4, IL-5, IL-10, and IL-13 in BAL fluid were also significantly decreased after sST2 treatment. Airway hyperresponsiveness to methacholine was decreased when treated with both Anti-IL-33 and sST2.   Conclusions:  Anti-IL-33 antibody and sST2 has a therapeutic potential for allergic asthma.
Multilobar x-ray shadowing is an independent predictor of community-acquired pneumonia severity and mortality
Authors: Carly L. Griffin, Joanne M. Sloan, Janet R. Wilson, James D. Chalmers, Morven E.M. Wilkie, Stuart Schembri
Journal: European Respiratory Journal (2012)

Introduction 

National guidelines for community-acquired pneumonia (CAP) recommend the CURB65 score to assess severity and determine antibiotic therapy. CURB65 does not factor the radiographic extent of consolidation on chest x-ray. The aim of this study was to determine the prognostic value of classifying CAP into unilobar and multilobar consolidation.

Methods 

A retrospective study of patients admitted with CAP was performed over 6 months. CAP was confirmed as a new radiographic infiltrate. The primary outcome of the study was 30-day mortality.

Results 

210 patients (52% male) were included. Median age was 76 years. 62%(no=131) were classified as unilobar pneumonia compared to 38% (no=80) with multilobar CAP. A positive correlation was observed between multilobar consolidation and mortality by Kaplain meier analysis (p=0.01 by log rank test).

![Figure][1] 



Multivariable analysis, after adjusting for confounders, revealed that multilobar consolidation was independently associated with 30-day mortality (odds ratio 2.25 95% CI 1.03-4.92, p=0.02). This relationship persisted for 90-day mortality (odds ratio 1.99 95 % CI 1.01-4.02, p=0.04).

Conclusion 

Multilobar pneumonia was associated with increased 30-day mortality rate when compared to unilobar pneumonia. This confirms that multilobar pneumonia is an indicator of poor prognosis and that these patients, irrespective of CURB65 score, should be treated more aggressively.

 [1]: pending:yes
Effect of topical levocabastine on allergic and non‐allergic perennial rhinitis
Authors: P. H. van de Heyning, J. van Haesendonck, W. Creten, N. Rombaut
Journal: Allergy (1988)

Forty‐four patients, with symptoms of nasal obstruction, sneezing, itching and/or rhinorrhea, were entered into a placebo‐controlled, double‐blind study to evaluate the clinical efficacy of a topical antihistamine drug, levocabastine, applied 4 times a day for 14 days. At the end of the treatment the placebo patients were treated with levocabastine and the levocabastine patients were treated with beclomethasone dipropionate in a single‐blind design for another 14 days. This study showed that levocabastine is significantly more active than placebo with reference to nasal discharge and sneezing. Placebo application improved the symptom score. Levocabastine could not be proved to be more effective against nasal obstruction than placebo in the double‐blind trial. In the single‐blind setup, levocabastine resulted in an additional improvement in the score for obstruction, after the placebo period. Although the allergic group tended to respond better, no statistically significant difference could be detected between allergic and non‐allergic patients. After treatment with levocabastine, beclomethasone dipropionate administration could not improve the results for nasal discharge and sneezing. For nasal congestion, beclomethasone dipropionate proved to be superior to levocabastine.
Assessment of lung perfusionusing computed tomography and perfusion scintigraphy in bronchial stenosis
Authors: Hiroki Nishine, Takehiko Hiramoto, Shin Matsuoka, Hiromi Muraoka, Okamoto Mariko, Teppei Inoue, Naoki Furuya, Hiroshi Handa, Hirotaka Kida, Seiichi Nobuyama, Takeo Inoue, Masamichi Mineshita, Teruomi Miyazawa
Journal: European Respiratory Journal (2014)

Background:  In central airway stenosis, stenting leads to an increase in bronchial patency and to the active distribution of ventilation. However, an improvement in blood flow and gas exchange has not yet been understood. The purpose of this study is to evaluate the distribution of pulmonary blood flow using computed tomography (CT) and perfusion scintigraphy. Methods:  We assessed lung perfusion in 8 patients with bronchial stenosis. CT and perfusion scintigraphy were performed before and after interventional bronchoscopy. We measured the cross-sectional area (CSA) of less than 5 mm 2  (CSAl5), 10 mm 2  (CSAl10), and 100 mm 2  (CSAl100) by computed tomography. The scintigraphic lung image was divided into the right and left lung. The distribution of lung perfusion was calculated to express the mean counts for the respective lungs as a percentage of the total counts in both lungs. Results:  In patients with bronchial stenosis, perfusion was reduced at the obstructed area. After intervention, two different findings were obtained depending on the duration of obstruction. When airway obstruction occurred for less than 1 month, perfusion immediately improved due to better ventilation. In patients with long-term lung collapse, perfusion was still severely reduced at the obstructed area. Three month later, CT and perfusion scintigraphy showed an improvement in blood flow. CSAl5, CSAl10 and CSAl100 were significantly correlated with the distribution of lung perfusion (r=-0.67, Pl0.01; r=-0.71, Pl0.01; r=-0.66, Pl0.01, respectively). Conclusions: Interventional bronchoscopy improved blood flow and gas exchange. CT and perfusion scintigraphy were useful in the assessment of regional blood flow.
Dose-intensification does not improve outcome in aggressive non-Hodgkin's lymphoma (NHL). Report of a randomized trial by the Australasian Leukemia and Lymphoma Group (ALLG).
Authors: M Wolf, J Matthews, J Stone, W Benson, P Browett, G Dart, E Abdi, A Grigg, J Ding, H Gurney, A Bonaventura, P Marlton, R Herrmann, D Ellis, Allg
Journal: Blood (2000)
Drug resistant tuberculosis in urban hotspot
Authors: T.K. Jayalakshmi, Aparna Iyer, Girija Nair
Journal: European Respiratory Journal (2014)

Background:Poverty and overcrowding in urban slums creates hot spots for initial drug resistant tuberculosis. One such area is the M (east) ward in Mumbai, India.  Aim:  1. To identify factors for drug resistant TB in urban slums  2. Study resistance patterns to anti-TB drugs  Method: Retrospective analysis of records at a tertiary care hospital in Navi Mumbai was done. Patients from M (east) ward in Mumbai were included. Multidrug resistant (MDR) and extensively drug resistant (XDR) TB were diagnosed by analysis of sputum/relevant samples by Line probe assay, liquid culture and sensitivity.  Results:  38 patients (23 men,15 women), had drug resistant TB. 33(84%) had MDR, 5(16%) XDR TB. No HIV/diabetes.  Initial drug resistance - MDR-5/33 (15%). XDR-1/5(20%).  Contact history- 6/38 (15%) cases.  Causes identified in each group-  Drug resistance:  High degree of initial drug resistance to quinolones found in MDR(67%) patients.  Conclusion: 1.50% of patients in urban slum area with drug resistant TB had no identified cause.  2. High prevalence of drug resistance in the community contributes to this .  3. 67% MDR isolates resistant to quinolones.  4. Drug susceptibility at the outset will be useful in such areas.
Hypoxia during endoscopy also occurs in unsedated patients
Authors: M W R Reed, C S Reilly
Journal: BMJ (1995)

Despite these findings and the well documented data on adults, pulse oximetry and cardiac monitoring have not been universally used in children undergoing endoscopy under sedation.4Clearly, if paediatric endoscopy is performed in this way similar recommendations concerning careful monitoring and supplemental oxygen must apply.There is, however, a safer and possibly better alternative.After witnessing several major hypoxic events and a respiratory arrest in centres where paediatric gastrointestinal endoscopy is performed under sedation, we have made it our policy to undertake these procedures under short general anaesthesia.This permits both detailed cardio- respiratory monitoring and constant supervision of the patient's airway by the anaesthetist.The procedure is well tolerated (and much preferred by those who have previously undergone endoscopy or jejunal biopsy under sedation) and can usually be carried out on a day case basis.General anaes- thesia allows the endoscopist to concentrate on the examination without distraction, and therapeutic interventions such as dilatation of an oesophageal stricture or injection of oesophageal varices can be undertaken during the same session.In a personal audit of over 300 diagnostic or therapeutic flexible gastrointestinal endoscopies performed in children aged 1 month to 17 years under general anaesthesia since January 1994 there were no major adverse events and all patients recovered fully.The patients included children with severe cerebral palsy, congenital heart disease, and other complex medical problems, who are at greater risk of cardiorespiratory disturbances.
Transplantation Immunity and Cross-Protection of Two Cultured Murine Colon Lines&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: N Sato, M C Michaelides, M K Wallack
Journal: JNCI Journal of the National Cancer Institute (1983)

Previous comparative investigations of the in vivo biology of two cultured colon tumors of BALB/c origin, C-C26 and C-C36, demonstrated different biologic activities. For elucidation of these differences, this report investigated the immunogenicity of these lines in providing protection to a subsequent challenge with different doses of tumor cells. Furthermore, the specificity of this protection was evaluated with cross-protection experiments. Our findings demonstrated these lines to be immunogenic and suggested the presence of cross-reactive tumor rejection-type antigens on these 2 cultured colon tumor lines. BALB/c mice immunized with these tumors developed resistance to challenge with the same tumor as well as to challenge with the other colon tumor lines. Further definition of these putative antigens could provide us with a better understanding for the diagnosis and treatment of colon tumors.
Spreading spondyloarthritis: are ILCs cytokine shuttles from base camp gut?
Authors: Barbara Neerinckx, Dirk Elewaut, Rik J Lories
Journal: Annals of the Rheumatic Diseases (2015)

A series of discoveries has transformed concepts of spondyloarthritis and pro--inflammatory cytokine interleukin--23 (IL--23) has taken center stage.The IL--23 frenzy kicked off with the identification of SNPs in the IL--23 receptor (IL23R) gene that are associated with ankylosing spondylitis (AS) 1 and also with related disorders such as psoriasis, psoriatic arthritis and Crohn's disease.The most striking and direct evidence comes from an in vivo IL--23 overexpression study in mice that phenocopies the human disease and its Janus--faced characteristics: joint inflammation and structural damage presenting as new bone formation 2 .Patient studies reported increased serum levels of IL--23 in AS 3--5 and presence of IL--23 positive cells was shown in facet joints of AS patients 6 .Direct clinical evidence comes from a prospective, open--label clinical trial with ustekinumab, an antibody binding to the shared p40 subunit of IL--23 and IL--12 7 and successful clinical trials targeting IL--17, one of the downstream cytokines associated with IL--23 signaling 8 .Key to the hypothesis and evidence proposed in the mouse model, is the presence of an IL--23 receptor positive T--cell population in the enthesis of mice.As enthesitis is one of the main characteristics of AS and was proposed as the primary lesion 9 , it is hard to ignore the potential key role of such cells.However, until now, these IL--23 receptor positive cells have not yet been demonstrated in human samples.In this issue of ARD, Ciccia and colleagues report on the presence of a population of IL--23R positive innate lymphoid cells (ILCs) in the gut, peripheral blood, synovial fluid and bone marrow of AS patients 10 .Numbers of such cells are increased as compared to different controls and their surface characteristics show similarities with the mouse cells identified earlier.However, these ILCs are a rare cell type whose significance in human disease is as yet uncertain.In two previous studies Ciccia et al showed increased IL--23 expression in the gut of AS patients as compared to healthy controls 11,12 .In AS synovium and peripheral blood cells however, no differences in expression of IL--23 were found 13,14 .They characterized these cells as Lyn --IL--23R + NKp44 + Tbet + RORc --cells and their induced production of cytokines IL--17 and IL--22 led them to conclude these are ILC3 cells.Unlike conventional ILC3 and IL--23R + entheseal T cells, these cells seemingly do not express RORc but do express the transcription factor Tbet which can, according to the authors, possibly be explained by a specific stage of differentiation of these cells.This finding makes them somewhat atypical, even for ILC3s.The reasons of these differences between 'conventional' characteristics of ILCs and the spondyloarthritis' associated cells are unclear and whether these changes precede onset of inflammation or are rather a secondary to already established inflammation remains to be determined.Further clarification of
IFNL4 ss469415590 polymorphism is associated with unfavourable clinical and immunological status in HIV-infected individuals
Authors: K. Machmach, C. Abad-Molina, M.C. Romero-Sánchez, B. Dominguez-Molina, M. Moyano, M.M. Rodriguez, M. Rafii-El-Idrissi Benhnia, M.E. Jimenez-Mejias, F. Vidal, M.A. Muñoz-Fernández, M. Genebat, P. Viciana, M.F. González-Escribano, M. Leal, E. Ruiz-Mateos
Journal: Clinical Microbiology and Infection (2014)