tbuckley/cabot-search huggingface dataset:
Brief Report: Responses to Rituximab Suggest B Cell–Independent Inflammation in Cutaneous Systemic Lupus Erythematosus
Authors: Edward M. Vital, Miriam Wittmann, Sara Edward, Md Yuzaiful Md Yusof, Helen MacIver, Colin T. Pease, M. Goodfield, Paul Emery
Journal: Arthritis & Rheumatology (2015)

The immunopathogenesis of systemic lupus erythematosus (SLE) is heterogeneous, and responses of skin to rituximab are variable. This study was undertaken to determine the phenotype of rituximab-responsive disease.Eighty-two patients with SLE who were receiving rituximab were prospectively studied. Of these patients, 32 had significant skin involvement before or after treatment. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index 2004. Cutaneous lupus subtype was classified by a dermatologist as acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CCLE), or other skin diseases, with supportive photographs or biopsies where necessary.Of 26 patients with skin disease at baseline, 9 (35%) had a beneficial mucocutaneous response to rituximab at 6 months, with good responses in ACLE (6 of 14 patients [43%]), and poor responses in CCLE (0 of 8 patients) (P = 0.034). Clinical response was associated with anti-RNP negativity (P = 0.024) and anti-Ro negativity (P = 0.031). Flares of SCLE and CCLE occurred in 12 patients who either had no skin disease or had ACLE at baseline (i.e., a switch in subtype). Concomitant antimalarials or conventional immunosuppressants were not associated with response or flare rate. Posttreatment biopsies confirmed typical active SLE histology in lesions occurring during B cell depletion.Our findings indicate that the clinical response to rituximab in cutaneous manifestations of SLE depends on subtype. None of the CCLE patients responded, and new CCLE lesions were observed during B cell depletion, suggesting that initiation and activity of these lesions is not B cell dependent. Flares of a range of skin diseases after B cell depletion may indicate a change in immune regulation following B cell-targeted therapy.
Soluble Receptor for Advanced Glycation End-Products Predicts Impaired Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome
Authors: Matthieu Jabaudon, Raiko Blondonnet, Laurence Roszyk, Damien Bouvier, Jules Audard, Gael Clairefond, Mathilde Fournier, Geoffroy Marceau, Pierre Déchelotte, Bruno Pereira, Vincent Sapin, Jean-Michel Constantin
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema but is impaired in most patients with ARDS. No reliable marker of this process has been investigated to date.To verify whether sRAGE could predict AFC during ARDS.Anesthetized CD-1 mice underwent orotracheal instillation of hydrochloric acid. At specified time points, lung injury was assessed by analysis of blood gases, alveolar permeability, lung histology, AFC, and plasma/bronchoalveolar fluid measurements of proinflammatory cytokines and sRAGE. Plasma sRAGE and AFC rates were also prospectively assessed in 30 patients with ARDS.The rate of AFC was inversely correlated with sRAGE levels in the plasma and the bronchoalveolar fluid of acid-injured mice (Spearman's ρ = -0.73 and -0.69, respectively; P < 10(-3)), and plasma sRAGE correlated with AFC in patients with ARDS (Spearman's ρ = -0.59; P < 10(-3)). Similarly, sRAGE levels were significantly associated with lung injury severity, and decreased over time in mice, whereas AFC was restored and lung injury resolved.Our results indicate that sRAGE levels could be a reliable predictor of impaired AFC during ARDS, and should stimulate further studies on the pathophysiologic implications of RAGE axis in the mechanisms leading to edema resolution. Clinical trial registered with www.clinicaltrials.gov (NCT 00811629).
Persistence of subclinical sonographic joint activity in rheumatoid arthritis in sustained clinical remission
Authors: M Gärtner, F Alasti, G Supp, P Mandl, J S Smolen, D Aletaha
Journal: Annals of the Rheumatic Diseases (2015)

Sonographic assessment, measuring grey scale (GS) and power Doppler (PD) signals, is a sensitive tool for the evaluation of inflammatory joint activity in patients with rheumatoid arthritis (RA). We evaluated the persistence of PD and GS signals in previously clinically active RA joints that have reached a state of continuous clinical inactivity.We performed sonographic imaging of 22 joints of the hands of patients with RA, selected all joints without clinical activity but showing ongoing sonographic signs of inflammation, and evaluated the time from last clinical joint activity.A total of 90 patients with RA with 1980 assessed joints were included in this study. When comparing the mean time from clinical swelling, we found a significantly longer period of clinical inactivity in joints showing low sonographic activity (mean±SD time from swelling of 4.1±3.2 vs 3.1±2.9 years for PD1 vs PD≥2, p=0.031 and 4.5±3.4 vs 3.3±3.2 years for GS1 vs GS≥2, p≤0.0001).We conclude that subclinical joint activity is long-lasting in RA joints in clinical remission, but attenuates over time. The latter conclusion is based on the observed shorter time duration from last clinical activity for strong compared with weaker sonographic signals.
Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma.
Authors: P McLaughlin, F B Hagemeister, J E Romaguera, A H Sarris, O Pate, A Younes, F Swan, M Keating, F Cabanillas
Journal: Journal of Clinical Oncology (1996)

Although most patients with indolent lymphomas respond to initial therapy, virtually all experience relapse. Secondary therapy is often beneficial, but responses are rarely, if ever, durable. We conducted this phase II trail to evaluate the therapeutic efficacy and toxicity of fludarabine, mitoxantrone, and dexamethasone (FND) in patients with relapsed indolent lymphoma.Fifty-one patients with recurrent or refractory indolent lymphoma were treated with a regimen of fludarabine 25 mg/m2/d intravenously (IV) on days 1 to 3, mitoxantrone 10 mg/m2 IV on day 1, and dexamethasone 20 mg/d IV or orally on days 1 to 5. Treatment was repeated at 4-week intervals for a maximum of eight courses. Late in the course of this trial, trimethoprim-sulfamethoxazole (TMP-SMX) was incorporated for Pneumocystis carinii (PCP) prophylaxis.Responses were complete (CR) in 24 patients (47%) and partial (PR) in 24 (47%). The median failure-free survival time was 21 months for CR patients and 9 months for PR patients. Notable activity of FND was seen even in the elderly, in those with high serum lactate dehydrogenase (LDH) or beta2-microglobulin levels, and in those with multiple prior treatment regimens. The predominant toxic effects were myelosuppression and infections; other toxic effects were modest. Infections occurred in 12% of courses. Almost half of the infections were proven or suspected opportunistic infections, including six cases of dermatomal herpes zoster and two cases of proven PCP pneumonia.The FND combination is highly active in patients with recurrent or relapsed indolent lymphoma and results in a high percentage of CRs. Because of the risk of opportunistic infections, we currently recommend prophylaxis with TMP-SMX and advise deletion of corticosteroids for patients who develop opportunistic infections.
Differential regulation of innate immunity in healthy smokers
Authors: Johan Öckinger, Michael Hagemann-Jensen, Susanna Kullberg, Anders Eklund, Johan Grunewald, Jan Wahlström
Journal: European Respiratory Journal (2013)

Recent studies have shown that a smoking increases the risk for autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. The mechanism underlying the risk increase is not known, but we hypothesized that tobacco smoke exposure could modulate the innate immune response, both systemically and in the lungs. This was investigated by a comprehensive analysis of innate immune response, including TLR signaling and inflammasome activation, in alveolar macrophages collected through bronchoalveolar lavage (BAL) from healthy smokers and non-smokers.  Our results indicate that key components for a functional inflammasome response, including NLRP3 and pro-IL-1β are upregulated in alveolar macrophages from healthy smokers, compared to non-smokers. In contrast, in vitro stimulation of BAL-cells with known inflammasome activators (e.g. LPS and ATP) induced a lower secretion of IL-1β from both BAL-cells and peripheral blood monocytes. In contrast, TNF expression is significantly downregulated in smokers and is inversely correlated to quantity of smoking within the group of smokers whereas other proinflammatory cytokines such as IL-6 and IL-8, and the receptors TLR2 and 4 are not differently expressed.  These results give further insight into the regulation of the immune response in the airways by tobacco smoke exposure, and will be follow by in-dept analysis of chromatin remodeling and transcriptional regulation of central pathways in the innate immune response.
Proteasome inhibition as a novel mechanism of the proapoptotic activity of γ-secretase inhibitor I in cutaneous T-cell lymphoma
Authors: E. Biskup, M.R. Kamstrup, V. Manfé, R. Gniadecki
Journal: British Journal of Dermatology (2013)

Background We have previously discovered that Notch1 is expressed on malignant T cells in cutaneous T‐cell lymphoma (CTCL), and is required for survival of CTCL cell lines. Notch can be inhibited by γ‐secretase inhibitors (GSIs), which differ widely in their ability to induce apoptosis in CTCL. Objectives To investigate whether GSI‐I, in addition to inhibiting Notch, induces apoptosis in CTCL by proteasome inhibition, as GSI‐I is very potent and has structural similarity to the proteasome inhibitor MG‐132. Methods Cell lines derived from CTCL (MyLa, SeAx, JK, Mac1 and Mac2a) were treated with GSI‐I and two other proteasome inhibitors (MG‐132 and bortezomib). The effects on cell viability, apoptosis and proteasome activity were measured, as was the impact on the prosurvival, nuclear factor κB (NF‐κB) pathway. Results In CTCL, GSI‐I had proteasome‐blocking activity with a potency comparable to the proteasome inhibitors MG‐132 and bortezomib. Proteasome inhibition was the main mechanism responsible for GSI‐I‐induced cell death, as tiron, a compound known to reverse the effect of MG‐132, restored proteasome activity and largely abrogated the cytotoxic effect of GSI‐I. Although inactivation of NF‐κB is an important mechanism of action for proteasome inhibitors, we demonstrated an apparent activation of NF‐κB. Furthermore, we showed that while the tumour suppressor protein p53 was induced during proteasome inhibition, it was dispensable for CTCL apoptosis, as both SeAx cells, which harbour p53 mutations that attenuate the apoptotic capacity, and HuT‐78 cells, which have a deleted p53 gene, demonstrated potent apoptotic response. Conclusions GSI‐I represents an interesting drug with a dual mechanism of action comprising inhibition of both Notch and the proteasome.
Association of FCER2 polymorphism with IgE levels and exacerbations in asthmatic children
Authors: Verónica Giubergia, Verónica Araoz, Claudio Castaños, Lilien Chertkoff
Journal: European Respiratory Journal (2014)

New evidence suggests that polymorphisms in the low-affinity IgE receptor ( FCER2 ) were associated with IgE levels and with increased risk of asthma exacerbation in children taking inhaled corticosteroids (ICS).

Objectives: To evaluate the association of FCER2 variant (T2206C) with IgE levels in asthmatic children and, to determine the influence of this variant on exacerbations in patients with severe asthma taking ICS and LABAs.

Methods: Children with mild, moderate and severe asthma (n 222) were genotyped for T2206C variant by PCR-RFLP. IgE levels were measured by ELISA and aged-adjusted values were determined for each individual. The number of severe exacerbations, the time of first exacerbation, number of hospitalizations and pulmonary function over 12 months were assessed in the severe group (n 99).

Results: The C allele frequency was significantly lower than the observed in other Caucasian populations (0.17, p<0.0001)1. A significant difference of IgE levels was observed among FCER2 variants with the highest value in the CC group (12.4 times over normal values) compared with TT (9) and TC (10.3) groups (p<0.05). The number and severity of asthma exacerbations, the time to first exacerbation and hospitalizations were similar among different FCER2 variants. The analysis of FEV1 from baseline to the end of the study showed no differences among FCER2 genotypes.

Conclusions: CC genotype was significantly less frequent in Argentinean population and was associated with higher IgE levels. FCER2 variants not related to increased risk of having asthma exacerbations or lung function decline in severe asthmatic children taking ICS and LABAs regularly.

(1) Koster E. et al. Allergy 2011;66:1546–1552.
Diagnostic significance of the tumour markers CEA, CA 15–3 and CA 125 in malignant effusions in breast cancer
Authors: K. Kandylis, M. Vassilomanolakis, N. Baziotis, A. Papadimitriou, S. Tsoussis, A. Ferderigou, A.P. Efremidis
Journal: Annals of Oncology (1990)
Cytotoxic Effects of Free Fatty Acids on Ascites Tumor Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Israel Siegel, Tian 'Lin Liu, Edmond Yaghoubzadeh, Tom S. Keskey, Norbert Gleicher
Journal: JNCI Journal of the National Cancer Institute (1987)

Journal Article Cytotoxic Effects of Free Fatty Acids on Ascites Tumor Cells Get access Israel Siegel, Ph.D., Israel Siegel, Ph.D. 4 3Division of Reproductive Immunology, Mount Sinai Hospital Medical Center and Rush Medical College, Chicago, IL 60608. 4Address reprint requests to Dr. Siegel at his present address: Mount Sinai Medical Center, 4300 Alton Rd., Miami, FL 33140. Search for other works by this author on: Oxford Academic PubMed Google Scholar Tian 'Lin Liu, M.D., Tian 'Lin Liu, M.D. 3Division of Reproductive Immunology, Mount Sinai Hospital Medical Center and Rush Medical College, Chicago, IL 60608. Search for other works by this author on: Oxford Academic PubMed Google Scholar Edmond Yaghoubzadeh, M.D., Edmond Yaghoubzadeh, M.D. 3Division of Reproductive Immunology, Mount Sinai Hospital Medical Center and Rush Medical College, Chicago, IL 60608. Search for other works by this author on: Oxford Academic PubMed Google Scholar Tom S. Keskey, B.S., Tom S. Keskey, B.S. 3Division of Reproductive Immunology, Mount Sinai Hospital Medical Center and Rush Medical College, Chicago, IL 60608. Search for other works by this author on: Oxford Academic PubMed Google Scholar Norbert Gleicher, M.D. Norbert Gleicher, M.D. 3Division of Reproductive Immunology, Mount Sinai Hospital Medical Center and Rush Medical College, Chicago, IL 60608. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 78, Issue 2, February 1987, Pages 271–277, https://doi.org/10.1093/jnci/78.2.271 Published: 01 February 1987 Article history Received: 05 December 1985 Revision received: 28 July 1986 Accepted: 08 August 1986 Published: 01 February 1987
Predictors of Recurrent AKI
Authors: Edward D Siew, Sharidan K Parr, Khaled Abdel-Kader, Svetlana K Eden, Josh F Peterson, Nisha Bansal, Adriana M Hung, James Fly, Ted Speroff, T Alp Ikizler, Michael E Matheny
Journal: Journal of the American Society of Nephrology (2015)

Recurrent AKI is common among patients after hospitalized AKI and is associated with progressive CKD. In this study, we identified clinical risk factors for recurrent AKI present during index AKI hospitalizations that occurred between 2003 and 2010 using a regional Veterans Administration database in the United States. AKI was defined as a 0.3 mg/dl or 50% increase from a baseline creatinine measure. The primary outcome was hospitalization with recurrent AKI within 12 months of discharge from the index hospitalization. Time to recurrent AKI was examined using Cox regression analysis, and sensitivity analyses were performed using a competing risk approach. Among 11,683 qualifying AKI hospitalizations, 2954 patients (25%) were hospitalized with recurrent AKI within 12 months of discharge. Median time to recurrent AKI within 12 months was 64 (interquartile range 19–167) days. In addition to known demographic and comorbid risk factors for AKI, patients with longer AKI duration and those whose discharge diagnosis at index AKI hospitalization included congestive heart failure (primary diagnosis), decompensated advanced liver disease, cancer with or without chemotherapy, acute coronary syndrome, or volume depletion, were at highest risk for being hospitalized with recurrent AKI. Risk factors identified were similar when a competing risk model for death was applied. In conclusion, several inpatient conditions associated with AKI may increase the risk for recurrent AKI. These findings should facilitate risk stratification, guide appropriate patient referral after AKI, and help generate potential risk reduction strategies. Efforts to identify modifiable factors to prevent recurrent AKI in these patients are warranted.
Efficacious and safe management of moderate to severe scalp seborrhoeic dermatitis using clobetasol propionate shampoo 0·05% combined with ketoconazole shampoo 2%: a randomized, controlled study
Authors: J.-P. Ortonne, A.F. Nikkels, K. Reich, R.M. Ponce Olivera, J.H. Lee, N. Kerrouche, F. Sidou, J. Faergemann
Journal: British Journal of Dermatology (2011)

Background Topical antifungals and corticosteroids are the mainstay of treatment for seborrhoeic dermatitis. The short-contact clobetasol propionate 0·05% shampoo (CP) is an efficacious and safe once-daily treatment for scalp psoriasis. Objectives To evaluate the efficacy and safety of CP alone and combined with ketoconazole shampoo 2% (KC) in the treatment of moderate to severe scalp seborrhoeic dermatitis. Methods This randomized and investigator-blinded study consisted of three phases, each lasting 4 weeks. During the treatment phase, subjects were randomized to receive KC twice weekly (K2), CP twice weekly (C2), CP twice weekly alternating with KC twice weekly (C2 + K2) or CP four times weekly alternating with KC twice weekly (C4 + K2). All subjects received KC once weekly during the maintenance phase and were untreated during the follow-up phase. Results At the end of the treatment phase, all three CP-containing regimens were significantly more efficacious than K2 in decreasing the overall disease severity (P < 0·05). Both combination regimens were also significantly more efficacious than K2 in decreasing each individual sign of the disease (P < 0·05). While the C2 and C4 + K2 groups experienced slight worsening during the maintenance phase, the efficacy of C2 + K2 was sustained and remained the highest among all groups. All regimens were well tolerated without inducing any skin atrophy. Similarly low incidences of telangiectasia, burning and adverse events were observed among the four groups. Conclusions The combination therapy of twice-weekly CP alternating with twice-weekly KC provided significantly greater efficacy than KC alone and a sustained effect in the treatment of moderate to severe scalp seborrhoeic dermatitis.
Association between Tobacco Smoking and Active Tuberculosis in Taiwan
Authors: Hsien-Ho Lin, Majid Ezzati, Hsing-Yi Chang, Megan Murray
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Previous case-control studies and a small number of cohort studies in high-risk populations have found an association between tobacco and active tuberculosis, but no cohort studies have been conducted in the general population on this association to date.To investigate the association between tobacco smoking and active tuberculosis in a cohort of a general population.17,699 participants (>or=12 y of age) in Taiwan National Health Interview Survey were followed up from 2001 to 2004. Smoking status and other covariates were measured by an in-person interview at baseline. Incident cases of active tuberculosis were identified from the National Health Insurance database. Multivariate logistic regression was used to estimate the association between smoking status and active tuberculosis, with adjustment for age, sex, alcohol consumption, socioeconomic status, and other covariates.Fifty-seven new cases of active tuberculosis occurred during the 3.3 years of follow-up. Current smoking was associated with an increased risk of active tuberculosis (adjusted odds ratio [OR], 1.94; 95% confidence interval, 1.01-3.73). The association was stronger among those less than 65 years of age (adjusted OR, 3.04) than those greater than 65 years of age (adjusted OR, 0.78; P(interaction) = 0.036). We found significant dose-response relations for cigarettes per day (P(trend) = 0.0036), years of smoking (P(trend) = 0.023), and pack-years (P(trend) = 0.0023).Tobacco smoking was associated with a twofold increased risk of active tuberculosis in a representative cohort of Taiwan's population.
Nintedanib Is a Highly Effective Therapeutic for Neuroendocrine Carcinoma of the Pancreas (PNET) in the Rip1Tag2 Transgenic Mouse Model
Authors: Ruben Bill, Ernesta Fagiani, Adrian Zumsteg, Helena Antoniadis, David Johansson, Simon Haefliger, Imke Albrecht, Frank Hilberg, Gerhard Christofori
Journal: Clinical Cancer Research (2015)

Pancreatic neuroendocrine tumors (PNET) represent a rare but challenging heterogeneous group of cancers with an increasing incidence over the last number of decades. Herein, we report an in-depth evaluation of the new antiangiogenic small-molecule tyrosine kinase inhibitor (TKI) nintedanib in the preclinical Rip1Tag2 transgenic mouse model of neuroendocrine carcinoma of the pancreas (insulinoma).We have assessed the antiangiogenic and antitumor activity of nintedanib, in comparison with other antiangiogenic TKI, by treating Rip1Tag2 transgenic mice with different treatment schedules complemented with histopathologic, cell biologic, and biochemical analyses.Prolonged nintedanib treatment of Rip1Tag2 mice has led to a strong suppression of angiogenesis, accompanied by a reduced tumor burden, which translated into a significant prolongation of survival. Despite nintedanib's inhibitory action on perivascular cells, the blood vessels remaining after therapy displayed a considerably mature phenotype with tight perivascular cell coverage and preserved perfusion. Nintedanib treatment did not increase local tumor invasiveness or metastasis to the liver and pancreatic lymph nodes--a phenomenon that has been observed with antiangiogenic treatments of Rip1Tag2 transgenic mice in other laboratories. In contrast with the strong reduction in blood microvessel densities, nintedanib did not have any impact on tumor lymphangiogenesis.Based on our findings, we propose the clinical evaluation of the antiangiogenic drug nintedanib as a new treatment modality for PNET patients, notably in a direct comparison with already established therapeutic regimens, such as sunitinib.
Spontaneous pneumopericardium related to active cytomegaloviral infection in a lung transplant recipient. The Groningen Lung Transplantation Group
Authors: GP Mannes, W van der Bij, WJ de Boer
Journal: European Respiratory Journal (1995)

Spontaneous pneumopericardium occurred in a patient almost 4 weeks after bilateral lung transplantation for cystic fibrosis. The patient had no specific complaints and was in stable haemodynamic condition. We suggest that this pneumopericardium was related to a concomitant active cytomegalovirus (CMV) infection. After treatment of the CMV infection, the pneumopericardium resolved spontaneously.