tbuckley/cabot-search huggingface dataset:
Effects of omalizumab on markers of eosinophilic inflammation in patients with severe allergic asthma
Authors: Marisa Hübner, Stephanie Korn, Matthias Jung, Ina Haasler, Christian Taube, Roland Buhl
Journal: European Respiratory Journal (2011)

Allergic asthma is a chronic inflammatory airway disease in which immunoglobulin E (IgE) and eosinophils play important pathogenetic roles.  We investigated the effect of the anti-IgE antibody omalizumab on markers of eosinophilic inflammation in patients with severe allergic asthma eligible for omalizumab treatment according to current guidelines. In 31 consecutive GINA step 4/5 patients (19 female, 48±11 yrs., 78±12 kg, 274±238 IU/ml total IgE, FEV1 at baseline 1.8±0.6 L, 61.8±19.5% pred.) omalizumab (median 450 mg/month) was administered s.c. as add-on therapy. Exhaled nitric oxide (NO), peripheral blood eosinophils and serum interleukin-5 were measured before and after 16 weeks of treatment. In all patients total daily doses of inhaled and oral corticosteroids remained stable during treatment.  23 (74%) patients responded to therapy (GETE). Baseline NO was 43±8 ppb (mean±SEM) for responders (R) and 23±6 ppb for non-responders (NR), blood eosinophils were 0.38±0.07/nl (R) and 0.25±0.06/nl (NR), and IL-5 was 7.5±1.13 (R) and 1.9±1.3 pg/ml (NR, R vs. NR p=0.030). After 16 weeks NO decreased by 3±6 ppb (R, p=0.804) and 12±18 ppb (NR, p=0.375), blood eosinophils were unchanged (R week0-week16: -0.14±0.16/nl, p=0.687; NR: 0.01±0.04/nl, p=1.000), and IL-5 decreased by 3.7±1.0 pg/ml (R, p=0.012) and 0.3±1.4 pg/ml (NR, p=0.625).  In conclusion, patients with a clinical response to omalizumab had higher pre-treatment serum IL-5 levels and a pronounced decrease in serum IL-5 following omalizumab. Blood eosinophils were unchanged, and exhaled NO was low prior and on treatment with omalizumab, consequent to high-dose ICS treatment.
Infusion of Light Chains From Patients With Cardiac Amyloidosis Causes Diastolic Dysfunction in Isolated Mouse Hearts
Authors: Ronglih Liao, Mohit Jain, Paige Teller, Lawreen H. Connors, Soeun Ngoy, Martha Skinner, Rodney H. Falk, Carl S. Apstein
Journal: Circulation (2001)

Background Primary (AL) amyloidosis is a plasma cell dyscrasia characterized by clonal production of immunoglobulin light chains (LC) resulting in the subsequent systemic deposition of extracellular amyloid fibrils. Cardiac involvement is marked by the hemodynamic pattern of impaired diastolic filling and restrictive cardiomyopathy. Although cardiac death in patients with AL amyloidosis is usually associated with extensive myocardial infiltration, the infiltration alone does not correlated with the degree of heart failure or survival. We hypothesized that circulating monoclonal LC may directly impair cardiac function, in addition to any mechanical effects of amyloid fibril deposition. Therefore, we examined the effects of amyloid LC proteins on diastolic and systolic cardiac function, as measured in an isolated mouse heart model. Methods and Results LC were obtained from patients with nonamyloid disease or from those with noncardiac, mild cardiac, and severe cardiac involved AL amyloidosis. Saline or LC (100 μg/mL) was infused into a Langendorff-perfused, isovolumically contracting mouse heart. Saline and control, noncardiac, and mild-cardiac LC infusions did not alter ex vivo cardiac function. In contrast, infusion of sever cardiac LC resulted in marked impairment of ventricular relaxation with preservation of contractile function. Conclusion These results demonstrate that infusion of LC from patients with AL amyloidosis result in diastolic dysfunction similar to that observed in patients with cardiac involved AL amyloidosis, and they suggest that amyloid LC proteins may contribute directly to the pathogenesis and the rapid progression of amyloid cardiomyopathy, independent of extracellular fibril deposition.
Aminoglycoside use for pseudomonas aeruginosa in bronchiectasis
Authors: Michele Fernandes, Timothy Gatheral, Ryan Dhunnookchand, Diana Bilton, Robert Wilson, Michael Loebinger
Journal: European Respiratory Journal (2014)

Summary  Pseudomonas aeruginosa  (PSA) is associated with increased morbidity in bronchiectasis (Bx). If intravenous antibiotic (IVABx) treatment is required, current guidance suggests the use of combination antibiotics (eg aminoglycoside) where there is the likelihood of repeated antibiotic courses. Patients with Bx are prone to the side effects of aminoglycosides.   Methods  This was a retrospective study of IVABx therapy in 98 consecutive Bx patients with PSA admitted 2010-12. Electronic patient records were used for outcomes. Time to next exacerbation was classified by category (0 = l1 month, 1 = 1-6 months, 2 = 6-12 months, and 3 = g 1year.) Data is presented as mean (SEM).   Results  Of 98 patients, 28 were admitted for PSA eradication and 70 for exacerbation. In total, 56% patients had combination antibiotics. Aminoglycoside was withheld in 43 patients because of hearing loss (22), intolerance (15), ageg70 (12), tinnitus (10), renal impairment (3), recent use (2), unrecorded (3). Of PSA exacerbation patients, 47.1% had an aminoglycoside. There was no significant difference in time to next exacerbation ((1.18(0.16) v 1.08(0.15), p= 0.6434) and number of exacerbations over the following year (2.12(0.19) v 2.22 (0.17), p=0.7118) with the use of aminoglycosides. A significantly higher proportion of PSA eradication patients (78.6%) had an aminoglycoside (Chi 2 : p=0.005). There was no significant difference in eradication success (68% (3mnth), 36% (6mnth), 25% (12mnth)).   Conclusions  In our specialist centre, 44% patients were unable to have aminoglycosides and had PSA monotherapy. There was no difference in outcome data. The rate of eradication success was low in this cohort that had previously failed ciprofloxacin.
Low‐Grade Inflammation in Symptomatic Knee Osteoarthritis: Prognostic Value of Inflammatory Plasma Lipids and Peripheral Blood Leukocyte Biomarkers
Authors: Mukundan Attur, Svetlana Krasnokutsky, Alexander Statnikov, Jonathan Samuels, Zhiguo Li, Olga Friese, Marie‐Pierre Hellio Le Graverand‐Gastineau, Leon Rybak, Virginia B. Kraus, Joanne M. Jordan, Constantin F. Aliferis, Steven B. Abramson
Journal: Arthritis & Rheumatology (2015)

Objective Inflammatory mediators, such as prostaglandin E 2 (PGE 2 ) and interleukin‐1β (IL‐1β), are produced by osteoarthritic (OA) joint tissue, where they may contribute to disease pathogenesis. We undertook the present study to examine whether inflammation, evidenced in plasma and peripheral blood leukocytes (PBLs), reflects the presence, progression, or specific symptoms of symptomatic knee OA. Methods Patients with symptomatic knee OA were enrolled in a 24‐month prospective study of radiographic progression. Standardized knee radiographs were obtained at baseline and 24 months. At baseline, levels of the plasma lipids PGE 2 and 15‐hydroxyeicosatetraenoic acid (15‐HETE) were measured, and transcriptome analysis of PBLs was performed by microarray and quantitative polymerase chain reaction. Results Baseline PGE 2 synthase (PGES) levels determined by PBL microarray gene expression and plasma PGE 2 levels distinguished patients with symptomatic knee OA from non‐OA controls (area under the receiver operating characteristic curve [AUC] 0.87 and 0.89, respectively, P &lt; 0.0001). Baseline plasma 15‐HETE levels were significantly elevated in patients with symptomatic knee OA versus non‐OA controls ( P &lt; 0.0195). In the 146 patients who completed the 24‐month study, elevated baseline expression of IL‐1β, tumor necrosis factor α, and cyclooxygenase 2 (COX‐2) messenger RNA in PBLs predicted higher risk of radiographic progression as evidenced by joint space narrowing (JSN). In a multivariate model, AUC point estimates of models containing COX‐2 in combination with demographic traits overlapped the confidence interval of the base model in 2 of the 3 JSN outcome measures (JSN &gt;0.0 mm, JSN &gt;0.2 mm, and JSN &gt;0.5 mm; AUC 0.62–0.67). Conclusion The inflammatory plasma lipid biomarkers PGE 2 and 15‐HETE identify patients with symptomatic knee OA, and the PBL inflammatory transcriptome identifies a subset of patients with symptomatic knee OA who are at increased risk of radiographic progression. These findings may reflect low‐grade inflammation in OA and may be useful as diagnostic and prognostic biomarkers in clinical development of disease‐modifying OA drugs.
Safety and Efficacy of Mpdl3280A (Anti-Pdl1) in Combination with Bevacizumab (Bev) and/or Chemotherapy (Chemo) in Patients (Pts) with Locally Advanced or Metastatic Solid Tumors
Authors: C. Lieu, J. Bendell, J.D. Powderly, M.J. Pishvaian, H. Hochster, S.G. Eckhardt, R. Funke, C. Rossi, D. Waterkamp, H. Hurwitz
Journal: Annals of Oncology (2014)
Identification of Cadherin 11 as a Mediator of Dermal Fibrosis and Possible Role in Systemic Sclerosis
Authors: Minghua Wu, Mesias Pedroza, Robert Lafyatis, Anuh‐Teresa George, Maureen D. Mayes, Shervin Assassi, Filemon K. Tan, Michael B. Brenner, Sandeep K. Agarwal
Journal: Arthritis & Rheumatology (2013)

Objective Systemic sclerosis (SSc) is a chronic autoimmune disease clinically manifesting as progressive fibrosis of the skin and internal organs. Recent microarray studies demonstrated that cadherin 11 (Cad‐11) expression is increased in the affected skin of patients with SSc. The purpose of this study was to examine our hypothesis that Cad‐11 is a mediator of dermal fibrosis. Methods Biopsy samples of skin from SSc patients and healthy control subjects were used for real‐time quantitative polymerase chain reaction analysis to assess Cad‐11 expression and for immunohistochemistry to determine the expression pattern of Cad‐11. To determine whether Cad‐11 is a mediator of dermal fibrosis, Cad‐11–deficient mice and anti–Cad‐11 monoclonal antibodies (mAb) were used in the bleomycin‐induced dermal fibrosis model. In vitro studies with dermal fibroblasts and bone marrow–derived macrophages were used to determine the mechanisms by which Cad‐11 contributes to the development of tissue fibrosis. Results Levels of messenger RNA for Cad‐11 were increased in skin biopsy samples from patients with SSc and correlated with the modified Rodnan skin thickness scores. Cad‐11 expression was localized to dermal fibroblasts and macrophages in SSc skin. Cad‐11–knockout mice injected with bleomycin had markedly attenuated dermal fibrosis, as quantified by measurements of skin thickness, collagen levels, myofibroblast accumulation, and profibrotic gene expression, in lesional skin as compared to the skin of wild‐type mice. In addition, anti–Cad‐11 mAb decreased fibrosis at various time points in the bleomycin‐induced dermal fibrosis model. In vitro studies demonstrated that Cad‐11 regulated the production of transforming growth factor β (TGFβ) by macrophages and the migration of fibroblasts. Conclusion These data demonstrate that Cad‐11 is a mediator of dermal fibrosis and TGFβ production and suggest that Cad‐11 may be a therapeutic target in SSc.
Delayed insertion of nasopharyngeal airway may result in failure to establish oral feeding and prolonged hospitalization in infants with Pierre Robin sequence
Authors: Jasneek Chawla, Fiona Ashton, Linda McCarthy
Journal: European Respiratory Journal (2012)

Introduction Nasopharyngeal airway support (NPA) is established as a safe, effective method of alleviating upper airway obstruction in infants born with the Pierre Robin Sequence (PRS). It is the preferred intervention for infants referred to our institution for respiratory assessment.  Aim To determine if timing of 1st NPA insertion affects duration of hospitalization for infants with PRS referred to RHSCE.  Methods A retrospective case note review of the management of infants referred to RHSCE with PRS from Oct 2009-Oct 2011 was performed.  Results 12 infants were included in this study. 7/12 infants were successfully discharged with NPA support. In 5/7 infants 1st NPA was inserted within 48hrs of admission and discharge occurred at a median of 15 days. In the other 2 infants, NPA was not inserted until day 6 & 10 of admission respectively. Only these 2 infants required nasogastric feeding on discharge. Parental training commenced on average 5 days later and these infants required up to a week longer in hospital. These delays did not however, impact on the timing of eventual cleft surgery.  3/12 infants were preterm and could not be managed initially with NPA due to small size. These infants all required a period of non-invasive ventilation and also had a longer hospital stay.  Conclusions Our results suggest that delayed insertion of NPA in infants with PRS may result in later establishment of oral feeding and prolonged hospitalization. NPA insertion within 48hrs of admission is suggested as optimum. Preterm infants are also identified as requiring a longer hospital stay with an alternative approach to airway management.
Abstract 4: The Effect of Prehospital Hypoxia and Hypotension on Outcome in Major Traumatic Brain Injury: A Deadly Combination
Authors: Daniel W Spaite, Uwe Stolz, Bentley J Bobrow, Vatsal Chikani, Duane Sherrill, Michael Sotelo, Bruce Barnhart, Joshua B Gaither, P D Adelson, Chad Viscusi, Terry Mullins, Will Humble, Kurt R Denninghoff
Journal: Circulation (2014)

BACKGROUND: Hypoxia (HOx) or hypotension (HT) occurring during the EMS management of major traumatic brain injury-TBI reduces survival. However, little is known about the impact of both HOx and HT, occurring together, on outcome. Only a handful of reports have studied the combination of prehospital HOx/HT in TBI and the largest of these only had 14 cases with both. Objectives: To evaluate the associations between mortality and prehospital HOx and HT, both separately and in combination. METHODS: All moderate/severe TBI cases (CDC Barell Matrix Type-1) in the Excellence in Prehospital Injury Care (EPIC) TBI Study (a statewide, before/after controlled study of the impact of implementing the EMS TBI Treatment Guidelines-NIH/NINDS: 1R01NS071049) from 1/1/08-6/30/12 were evaluated [exclusions: age&lt;10; death before ED arrival; EMS O2 saturation-“sat”&lt;11%; EMS SBP less than 40 or greater than 200; missing sat (5.4% of cases) or SBP (3.1% of cases)]. The relationship between mortality and HOx (sat &lt;90) and/or HT (SBP&lt;90) was assessed with crude and adjusted odds ratios (cOR, aOR) using multivariable logistic regression, controlling for important confounders (see Figure) and accounting for clustering by Trauma Center. RESULTS: 9194 cases were included [Median age: 46 (IQR: 26-65); Male: 68.1%]. 8109 (88.2%) had no HOx/HT, 535 (5.8%) had HOx only, 419 (4.6%) had HT only, and 131 (1.4%) had both HOx/HT. The Figure shows the cORs and aORs for death. CONCLUSION: In this large analysis of major TBI, prehospital HOx and HT were associated with significantly increased mortality. However, the combination of HT and HOx together had a profoundly-negative effect on survival even after controlling for significant confounders. In fact, the aOR for death in patients with both HOx/HT was more than 3 times greater than for those with HOx or HT alone. Since the TBI Guidelines emphasize the prevention and treatment of HOx and HT, their implementation has the potential to significantly impact outcome.
Human Cytomegalovirus Immediate-Early Protein IE2–86, but not IE1–72, Causes Graft Coronary Arteriopathy in the Transplanted Rat Heart
Authors: Ken Suzuki, Bari Murtuza, Noriko Suzuki, Mahboob Khan, Yasufumi Kaneda, Magdi H. Yacoub
Journal: Circulation (2002)

Background Graft coronary arteriopathy (GCA) after heart transplantation is a major factor limiting the long-term survival of the recipients. Human cytomegalovirus (HCMV) infection is a possible cause of this disease which is characterized by diffuse intimal thickening resulting from smooth muscle cell migration and proliferation. It has been reported that HCMV immediate-early (IE) proteins, IE1 and IE2, could play an important role in the development of this disease; however, the precise in vivo role of these proteins in causing GCA has not been clarified. Methods and Results Excised Lewis rat hearts were transfected with HCMV IE1–72, IE2–86 or control plasmid by intra-coronary infusion of Hemagglutinating Virus of Japan-liposome, and transplanted into syngeneic recipients’ abdomens. All cardiac grafts continued to beat well throughout the incubation period in the absence of immunosuppression. Exclusive expression of IE1–72 or IE2–86 protein in coronary artery walls was demonstrated after IE1–72 or IE2–86 gene transfection, respectively. Luminal occlusion as a consequence of intimal thickening of graft coronary arteries developed in the IE2–86 transfected hearts at day 21 after transplantation (30.1±3.4% occlusion, P &lt;0.0001), compared with the IE1–72 and control transfected ones (8.2±1.6 and 6.8±1.1%, respectively). In contrast, there was no significant difference in luminal occlusion between the IE1–72 and control transfected hearts. Conclusions We have demonstrated that expression of IE2–86 alone, but not IE1–72, causes intimal hyperplasia after cardiac transplantation. IE2–86 protein may therefore prove to be a useful target in therapies aimed at preventing HCMV-related GCA and improving the long-term result of cardiac transplantation.
Relationship between NT-proBNP level, echocardiographic parameters and cardiovascular diseases in patients with obstructive sleep apnoea (OSA)
Authors: Anna Czyzak-Gradkowska, Robert Plywaczewski, Monika Targowska, Luiza Jonczak, Przemyslaw Bielen, Pawel Sliwinski
Journal: European Respiratory Journal (2012)

Brain natriuretic peptide (BNP) is a hormone secreted by the ventricles in response to heart overload. The aim of this study was to assess prevalence of elevated NT-proBNP (inactive form of BNP) level in OSA patients and its relations to echocardiographic parameters and OSA-asociated cardiovascular complications. We studied 87 OSA pts, mean AHI was 43.2±24.1, age - 57.5 ±10.6 yrs, mean plasma NT-proBNP level was 198.5±357.3 pg/ml. Elevated NT-proBNP concentration was found in 34 pts with OSA. Comparison of OSA pts with normal and elevated NT-proBNP level is shown in a table below.

View this table:



Elevated NT-proBNP level was found in 39.8% OSA subjects. Logistic regression analysis revealed that elevated NT-proBNP level (>125pg/ml) did not correlate with studied echocardiographic parameters in OSA pts (p>0.05). NT-proBNP level negatively correlated with AHI (r =-0.25, p=0,02). Elevated NT-proBNP concetration indicated at increased risk of coronary artery disease (OR = 12.94, 95%CI = 2.4-68.5, p<0.01).

Conclusions: Increased plasma concentration of NT-proBNP was not related to echocardiographic parameters, but it was associated with occurence of CAD in OSA subjects.
How many times should overnight pulse-oximetry be undergone to screen obstructive sleep apnea syndrome?
Authors: Kensuke Sumi, Tomomasa Tsuboi, Mio Yamashita, Hisako Tabata, Shigeki Sakai, Masayoshi Minakuchi, Susumu Oguri, Atsuo Sato
Journal: European Respiratory Journal (2014)

Background: Overnight pulse-oximetry has been used for screening obstructive sleep apnea syndrome (OSAS). However, there is no evidence about how many times overnight pulse-oximetry should be done to efficiently select subjects for further examination such as polysomnography (PSG).  Methods: We recruited 89 subjects underwent both three consecutive night pulse-oximetry and one night PSG. Apnea hypopnea index (AHI) evaluated by PSG was compared to the largest 3% oxygen desaturation index (ODI3) measured by overnight pulse-oximetry. First, AHI was compared to ODI3 in the 1st night. Second, AHI was compared to larger ODI3 in the 1st and the 2nd nights. Finally, AHI was compared to the largest ODI3 in the 1st to the 3rd night. AHI more than 20 (events/hour) is used as a criterion for continuous positive airway pressure (CPAP) treatment in Japan. We set the cut off line ODI3 more than 10 (events/hour) to find out the patients with AHI more than 20.  Results: When using the largest ODI3 in the 1st to the 3rd night, the sensitivity for finding out the subjects with AHI more than 20 was 91.9%, and when using larger ODI3 in the 1st and the 2nd nights, the sensitivity was equally 91.9%. When using ODI3 in the 1st night, the sensitivity was 75.7%.  Conclusions: To select subjects for PSG adequately and economically, we should investigate overnight pulse-oximetry for two nights, and adopt the more serious result.
Waiting List Initiatives: Crisis Management or Targeting of Resources?
Authors: R P Mills, J M Heaton
Journal: Journal of the Royal Society of Medicine (1991)

To investigate the impact of a waiting list initiative on an ENT surgical waiting list, we have evaluated the outcome of the Tayside ENT Waiting List Initiative. Four hundred and forty-five patients were offered dates to come in during the initiative. Of these, 280 underwent surgery and 16 indicated that their operations were no longer necessary. The maximum wait for routine operations falling within the criteria for inclusion in the initiative was 28 months prior to the initiative and 7 months afterwards. A waiting list initiative can be effective in reducing waiting times for routine surgery. However, it is too early to describe the Tayside initiative as an unqualified success, as it remains to be seen whether or not the waiting list will lengthen again now that it is over.
Effect of pulmonary rehabilitation on erythrocyte oxidative stress and antioxidants in COPD patients
Authors: Kenji Nemoto, Masayuki Itoh, Seitaro Semba, Hideki Adachi, Koji Kishi, Hiroyuki Nakamura, Shuji Oh-ishi
Journal: European Respiratory Journal (2012)

Background and objective: Recent studies suggest that pulmonary rehabilitation (PR) is essential in the management of COPD. However, the effect of PR on oxidants and antioxidants in erythrocytes is only partially understood. The aim of this study was to evaluate whether PR improves not only exercise capacity and health-related quality of life (HRQL), but also the oxidant/antioxidant imbalance in erythrocytes.  Methods: Twelve stable COPD patients participated in PR for 8 weeks. A pulmonary function test, 6-minute walking test (6MWT), shuttle walk test (SWT), and the St. George9s Respiratory Questionnaire (SGRQ) were administered before and after PR. Blood was collected prior to and after PR for analysis of thiobarbituric acid-reactive substance (TBARS), superoxide dismutase (SOD), Cu-Zn-SOD, glutathione peroxidase (GPX), and total glutathione (TGSH).  Results: After PR, exercise capacity was improved (6MWT: 399.5±28.6 vs. 455.1±31.7 m,  P  P  P  P   Conclusions: The current study suggested that PR improved exercise capacity and HRQL and upregulated antioxidant capacity, resulting in no further increase with exercise therapy.