tbuckley/cabot-search huggingface dataset:
Baseline chest computed tomography scores correlate with future exacerbations in young children with cystic fibrosis
Authors: Carla-Federica Bortoluzzi, Sonia Volpi, Ciro D'Orazio, Martine Loeve, Harm A. Tiddens, Baroukh M. Assael
Journal: European Respiratory Journal (2013)

Background: Children with cystic fibrosis (CF) in early school age have often normal spirometry; more sensitive validated methods for early detection and monitoring of CF lung disease are needed.

Aim: To investigate whether chest computed tomography (cCT) score in early school age predicts respiratory tract exacerbation (RTE) number in the following 6 years with better accuracy than FEV1.

Methods: Routine cCT obtained in a single centre from 80 CF patients (mean age 8.2; range 4.3-15; mean pred FEV1 83.3%) were scored using CF-cCT scoring system. All patients were closely monitored in the following 6 years, RTE was defined as an intravenous antibiotic treatments for respiratory symptoms. We used Pearson coefficient to describe correlations with lung function parameters (FEV1and FEF25-75) at baseline and after 6 years. Receiver operating characteristic (ROC) curve analysis was used to test a cut off value for CF-cCT score.

Results: mean cCT score (sCTtot) and bronchiectasis subscore (sCTbr) were respectively 12.8 and 14.9 (% of max score). Mean number of RTE in 6 years was 2.2 (SD 3.6,range 0-22). We found good correlations between both sCTtot/sCTbr and RTE (R= 0.664 and 0.69 respectively, p<0.001). Baseline FEV1 showed a significant but weaker correlation with RTE in the following 6 years (R=0.49, p<0.001). Baseline FEV1 showed a poor correlation with sCTtot (R=0.424, p<0.001). Area under the ROC curve for sCTbr to detect ≥4 RTE was 0.907. A sCTbr ≥16.9 identified patients who experienced ≥4RTE in the following 6 years with sensitivity 94.1% and specificity 79.4%.

Conclusion : Bronchiectasis as diagnosed by cCT identify patients at higher risk of RTE.
Hyperprolactinemia and hypothyroidism following cytotoxic therapy for central nervous system malignancies.
Authors: L S Constine, P Rubin, P D Woolf, K Doane, C M Lush
Journal: Journal of Clinical Oncology (1987)

Endocrinologic dysfunction including hyperprolactinemia and hypothyroidism are recognized complications of irradiation to the hypothalamic-pituitary axis or thyroid gland in the course of treating CNS malignancies. However, the frequency of these adverse effects in both short- and long-term survivors may be underestimated. Sixty-five patients treated in the University of Rochester Cancer Center since 1968 with radiation with or without BCNU chemotherapy for CNS tumors not involving the hypothalamic-pituitary axis were evaluated for thyroid, prolactin, and gonadal disturbances regardless of clinical symptomatology. Prolactin values were elevated in 19 of 47 patients (40%). For males and females treated with greater than 55 Gy, abnormal values were present in nine of 11 (82%) and seven of 14 (50%), respectively. For males and females treated with less than or equal to 55 Gy, two of nine (22%) and one of 13 (8%), respectively, were abnormal (P = .0001). Six of six patients who also received BCNU chemotherapy were hyperprolactinemic, as compared with six of ten (60%) who did not receive BCNU. Seven of eight females with elevated prolactin levels had menstruation abnormalities, and five of seven adult males noted a decrease in libido. Mild abnormalities in testosterone concentration were found in three of nine men evaluated, all of whom had normal gonadotropins. Of 47 patients who did not receive irradiation to the spinal axis (and thus the thyroid gland), ten (21%) had a decreased thyroxin (T4) value. Only one of these patients had an elevated thyroid-stimulating hormone (TSH) value. Of 32 patients who received greater than 55 Gy, ten (31%) had a low T4, compared with zero of 15 who received less than or equal to 55 Gy (P = .0001). Four of eight patients (50%) who also received BCNU had low T4 values, as compared with three of 14 (21%) who did not receive BCNU. Of 15 patients who were treated with 4 to 10 MV photon irradiation to the spinal axis, five patients (33%) had elevated TSH values. The mean spinal axis dose in these patients was 33 Gy. Two euthyroid children in this group manifested the early onset of puberty. The complex of endocrinologic abnormalities observed in several patients receiving only cranial irradiation, that is elevated prolactin, decreased thyroid, and gonadal hormone secretion in the presence of otherwise normal pituitary hormone levels, suggests a radiation-induced insult to the hypothalamic regulation of pituitary function.
Tumor Growth in the Guinea Pig: Alpha Globulin Changes Associated With Lymphocyte Suppression 2
Authors: David P. Lilley, Denis R. Burger, R. Mark Vetto
Journal: JNCI Journal of the National Cancer Institute (1974)

Serum globulin changes associated with tumor growth and suppressed Iymphocyte responsiveness to mitogen stimulation were observed in strain-13 guinea pigs. Disc gel electrophoresis of serum hal'vested during growth of a transplanted, 3-methylcholanthrene-induced fibrosarcoma showed an increase in globulin fraction 4 in the α-globulin region. Globulin fraction 4 significantly rose by 16 days of tumor growth and remained elevated until the animals died. Concomitant with this increase, in vitro suppression of Iymphocyte reactivity to phytohemagglutinin and pokeweed mitogen was observed. Inhibition, measured by the level of 3H-thymidine incorporated into whole blood cultures, increased in severity until death of the animals. Direct correlations between progressive tumor growth, suppression of cell-mediated tumor immunity, and increases in disc gel fraction 4 were observed.
Abstract 2161: Impact of Target Lesion Revascularization During the First Year After Bare-Metal or Sirolimus-Eluting Stenting on Five-Year Cardiac Outcomes
Authors: Meredith Mulhearn, Victor Novack, Riya S Chacko, Lena Novack, Laura Mauri, Sidney A Cohen, Martin B Leon, Jeffrey Moses, Donald E Cutlip
Journal: Circulation (2007)

Background: The association of restenosis requiring target lesion revascularization (TLR) and late cardiac outcomes after drug-eluting versus bare metal stents (BMS) has not been previously assessed. Methods: We hypothesized that restenosis requiring TLR within 1 year after stenting would be associated with increased risk of adverse cardiac outcomes during the next 4 years. Of 1058 patients randomized to sirolimus-eluting (SES) or BMS in the SIRIUS trial, 37 were excluded due to multivessel (6) or SVG (1) stenting or the occurrence of TLR within the first 30 days (30), leaving 515 SES and 506 BMS. Patients with TLR for restenosis indication between 31–360 days after the index procedure (TLR group) were compared with all others (Non TLR group) for outcomes during years 2–5. The primary endpoint was a composite of cardiac death, any MI or any repeat revascularization. The secondary endpoint was cardiac death or any MI. All events were adjudicated by an independent committee. Event rates were estimated using Kaplan-Meier (KM) method and compared using log rank. The correlates of the primary and secondary endpoints were tested using Cox proportional hazards regression. Results: TLR occurred in 120 (11.8%) patients. TLR patients had lower frequency of SES (24.2% vs. 53.9%, p&lt;0.001), more diabetes (35.8% vs. 25.2%, p=0.02) and smaller diameter vessels (2.7±0.5 vs. 2.8±0.5 mm, p=0.04). TLR presented with MI in 7 (5.8%) patients, including CKMB &gt;5 times normal in 6 (5.0%) patients. The primary endpoint occurred in 42 (36.1%) TLR and 211 (24.3%) Non TLR patients (log-rank p = 0.002). Cardiac death or MI occurred in 16 (13.8%) TLR patients and 57 (6.6%) Non TLR patients (log-rank p = 0.005). TLR was an independent predictor of the primary endpoint (Hazard ratio [HR] 1.6, 95% CI 1.2–1.9) and of cardiac death or MI (HR 1.9, 95% CI 1.3–2.4). Other independent predictors of cardiac death or MI were diabetes (HR 2.2, 95% CI = 1.7–2.6) and prior MI (HR 1.9, 95% CI 1.3–2.4). SES compared with BMS was not significantly associated with the primary endpoint or cardiac death or MI. Conclusions: Restenosis requiring TLR during 31–360 days after successful stenting is associated with an increased risk of adverse outcomes, including cardiac death or MI, in subsequent years.
The course of spinal tuberculosis (Pott disease): results of the multinational, multicentre Backbone-2 study
Authors: A. Batirel, H. Erdem, G. Sengoz, F. Pehlivanoglu, E. Ramosaco, S. Gülsün, R. Tekin, B. Mete, İ.İ. Balkan, D.Y. Sevgi, E. Giannitsioti, A. Fragou, S. Kaya, B. Cetin, T. Oktenoglu, A.D. Celik, B. Karaca, E.S. Horasan, M. Ulug, S. Senbayrak, S. Kaya, E. Arslanalp, R. Hasbun, S. Ates-Guler, A. Willke, S. Senol, D. Inan, E. Güclü, G.T. Ertem, M.M. Koc, M. Tasbakan, G. Ocal, S. Kocagoz, H. Kusoglu, T. Güven, A.I. Baran, B. Dede, F.Y. Karadag, H. Yilmaz, G. Aslan, D.A. Al-Gallad, S. Cesur, R. El-Sokkary, F. Sirmatel, U. Savasci, G. Karaahmetoglu, H. Vahaboglu
Journal: Clinical Microbiology and Infection (2015)
Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients?
Authors: A Zoubek, B Dockhorn-Dworniczak, O Delattre, H Christiansen, F Niggli, I Gatterer-Menz, T L Smith, H Jürgens, H Gadner, H Kovar
Journal: Journal of Clinical Oncology (1996)

Because of the high heterogeneity of EWS gene fusions with FLI1 and ERG genes due to variable chromosomal breakpoint locations in Ewing tumors (ET) (14 different chimeric transcripts identified so far), we evaluated the clinical impact of the expression of diverse fusion transcripts in ET patients.In a European multicenter study, 147 ET were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and the molecular data statistically compared with all clinical data available.Most tumors expressed chimeric transcripts with fusion of EWS exon 7 to FLI1 exon 6 (75 of 147) (type I) or five (39 of 147) and EWS exon 10 to FLI1 exon 5 (eight of 147) or 6 (five of 147). In five cases, chimerism between EWS exon 9 and FLI1 exons 4 and EWS exon 7 and FLI1 exon 7 or 8 was observed. Fifteen cases of EWS-ERG rearrangement were identified. In 85 of these patients treated in the European Cooperative Ewing Sarcoma Studies, molecular results were analyzed in comparison to age, sex, tumor localization, tumor volume, and disease extension. No significant correlation between the various fusion types and these features were observed. Relapse-free survival (RFS) for the 31 patients with localized disease and fusion type I tended to be longer compared with the 24 patients with localized tumors bearing other chimeric transcripts (P = .04).Results suggest a possible advantage in PFS for patients with localized disease and fusion type I transcripts, although this will require prospective validation with a larger number of patients and longer follow-up periods.
S100-Beta, Melanoma-Inhibiting Activity, and Lactate Dehydrogenase Discriminate Progressive From Nonprogressive American Joint Committee on Cancer Stage IV Melanoma
Authors: Martin Deichmann, Axel Benner, Michael Bock, Andreas Jäckel, Karen Uhl, Volker Waldmann, Helmut Näher
Journal: Journal of Clinical Oncology (1999)

Monitoring advanced malignant melanoma, serum levels of S100-beta (S100beta) and melanoma-inhibiting activity (MIA) were assessed for the ability to discriminate progressive from nonprogressive disease. S100beta and MIA were supposed to be superior to conventional variables, such as lactate dehydrogenase (LDH) level.Seventy-one patients with stage IV malignant melanoma according to the criteria of the American Joint Committee on Cancer (AJCC) were included in the study. Results of restaging examinations were used as an independent reference standard for diagnosing progressive disease, and S100beta, MIA, LDH level, and erythrocyte sedimentation rate (ESR) were determined in venous blood just before restaging. Sensitivities and specificities of the parameters were calculated by logistic regression analysis. Discrimination ability was assessed by Somers' D(xy) rank correlation and the area under the receiver-operating characteristic curve (ROC-AUC).All tested serum parameters were significantly elevated in patients with progressive disease. The highest sensitivities according to the established thresholds were found for S100beta and MIA (91% and 88%, respectively). LDH had the highest specificity (92%). ESR was dropped from the analysis because of low specificity. In calculating Somers' D(xy) and ROC-AUC values, S100beta, MIA, and LDH showed high discrimination ability. By multiple logistic regression, LDH was identified to be the only statistically significant marker for progressive disease. S100beta and MIA did not provide additional significant information because of their high correlation with LDH with respect to clinical outcome.Elevated serum levels of S100beta, MIA, and LDH indicate current disease progression in AJCC stage IV melanoma. LDH was the most relevant overall parameter.
Treatment outcome and prognostic factors for primary nasal lymphoma.
Authors: R Liang, D Todd, T K Chan, E Chiu, A Lie, Y L Kwong, D Choy, F C Ho
Journal: Journal of Clinical Oncology (1995)

To report our experience managing a large series of Chinese patients with primary nasal lymphoma.From January 1975 to December 1993, 100 patients (median age, 50 years) with newly diagnosed primary nasal lymphoma were studied. There were four low-grade, 62 intermediate-grade, nine high-grade, and 25 unclassifiable lymphomas. Immunophenotyping was performed in 45 patients: eight B cell, 35 T cell, and two uncertain. All cases of angiocentric lymphoma that were typed were T cell. Fifty-two patients had stage I disease, 15 had stage II, four had stage III, and 29 had stage IV. Only 15 patients had B symptoms (weight loss, night sweats, and/or fever), and 11 had bulky disease. Thirty-nine patients with clinically localized stage I and II disease received local radiotherapy alone (before 1980), and the remaining 28 stage I and II patients received combination chemotherapy followed by local radiotherapy. The 33 patients with advanced stage III and IV disease were given combination chemotherapy, and additional radiotherapy was given to five of them who had bulky local disease.Significantly higher complete remission rates were observed in patients with early stages of disease and those without B symptoms. Superior disease-free survival after complete remission was observed in patients with stage I/II disease. Univariate factors associated with a better overall survival included age less than 60 years, stage I disease, and absence of B symptoms. Survival was significantly better in the subgroup of patients with stage I disease.Patients with nasal lymphoma, especially those with advanced disease, seemed to have a poor prognosis, and their clinical outcome was not improved significantly by the use of chemotherapy instead of radiotherapy or the use of doxorubicin-containing chemotherapeutic regimens.
Tuberculous spondylitis as a mirror of a severe epidemic situation
Authors: Ekaterina Kulchavenya, Eugenia Koveshnikova
Journal: European Respiratory Journal (2011)

Introduction: Tuberculosis of bone and joints (BJTB) is one of the leading forms among extrapulmonary TB. The aim was to estimate a spectrum of extrapulmonary TB in Novosibirsk – the capital of Siberia, and reveal a tendency in BJTB.  Material and methods: Statistical reports were estimated, also 177 patients with BJTB were enrolled in study.  Results: Among all cohort of extrapulmonary TB female patients was 50.9% and male patients - 49.1%, but in BJTB ration female:male was 1:2.  The share of BJTB in extrapulmonary TB increased from 3.3% in 1992 up to 28.0% in 2006, and reached 48.6% in 2008. Among BJTB tuberculous spondylitis prevails (72.2%), mostly complicated by neurological disorders and parevertebral abscesses and combined with TB of other organs. Nevertheless in 65.5% only 2 vertebrae were involve in TB process. In 17.2 debut of disease was acute or sub-acute, but diagnostic took 14.1 months on average. One of the main reason is poor alertness physician for tuberculosis and late X-ray examination. Typical X-ray picture of TB spondylitis is shown on figure 1.  Poverty, unemployment and alcoholism resulted in poor efficiency of the therapy in 43.7% patients. Patients endomorphic body type in 8.5 times more likely to have delayed consolidation.  Conclusion: In regions with severe epidemic situation it is necessary always to keep in the mind TB in patients with back pain and make X-ray examination as soon as possible.
Effects of Donor Age on Neoplastic Transformation of Adult Mouse Bladder Epithelium In Vitro
Authors: I C Summerhayes, L M Franks
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Effects of Donor Age on Neoplastic Transformation of Adult Mouse Bladder Epithelium In Vitro Get access I. C. Summerhayes, I. C. Summerhayes Search for other works by this author on: Oxford Academic PubMed Google Scholar L. M. Franks L. M. Franks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 62, Issue 4, April 1979, Pages 1017–1023, https://doi.org/10.1093/jnci/62.4.1017 Published: 01 April 1979 Article history Received: 30 May 1978 Accepted: 14 September 1978 Published: 01 April 1979
Stability of Vitamins in a Chemically Defined Medium for 929-L Fibroblasts&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Joyce Mohberg, Marvin J. Johnson
Journal: JNCI Journal of the National Cancer Institute (1963)

Journal Article Stability of Vitamins in a Chemically Defined Medium for 929-L Fibroblasts Get access Joyce Mohberg, Joyce Mohberg Department of Biochemistry, University of Wisconsin, Madison 6, Wisconsin Search for other works by this author on: Oxford Academic PubMed Google Scholar Marvin J. Johnson Marvin J. Johnson Department of Biochemistry, University of Wisconsin, Madison 6, Wisconsin Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 31, Issue 3, September 1963, Pages 603–610, https://doi.org/10.1093/jnci/31.3.603 Published: 01 September 1963 Article history Received: 06 February 1963 Published: 01 September 1963
Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials
Authors: K.A. Papp, M.A. Menter, M. Abe, B. Elewski, S.R. Feldman, A.B. Gottlieb, R. Langley, T. Luger, D. Thaci, M. Buonanno, P. Gupta, J. Proulx, S. Lan, R. Wolk
Journal: British Journal of Dermatology (2015)

Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis.To determine the 16-week efficacy and safety of two oral tofacitinib doses vs. placebo in patients with moderate-to-severe chronic plaque psoriasis.Patients in two similarly designed phase III studies (OPT Pivotal 1, NCT01276639, n = 901; OPT Pivotal 2, NCT01309737, n = 960) were initially randomized 2 : 2 : 1 to tofacitinib 10 or 5 mg or placebo, twice daily. Coprimary efficacy end points (week 16) included the proportion of patients achieving Physician's Global Assessment (PGA) of 'clear' or 'almost clear' (PGA response) and the proportion achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75).Across OPT Pivotal 1 and OPT Pivotal 2, 745 patients received tofacitinib 5 mg, 741 received tofacitinib 10 mg and 373 received placebo. At week 16, a greater proportion of patients achieved PGA responses with tofacitinib 5 and 10 mg twice daily vs. placebo (OPT Pivotal 1, 41·9% and 59·2% vs. 9·0%; OPT Pivotal 2, 46·0% and 59·1% vs. 10·9%; all P < 0·001). Higher PASI 75 rates were observed with tofacitinib vs. placebo (OPT Pivotal 1, 39·9%, 59·2% and 6·2%, respectively, for tofacitinib 5 and 10 mg twice daily and placebo; OPT Pivotal 2, 46·0%, 59·6% and 11·4%; all P < 0·001 vs. placebo). Adverse event (AE) rates appeared generally similar across groups; rates of serious AEs, infections, malignancies and discontinuations due to AEs were low. Twelve patients reported herpes zoster across the tofacitinib treatment groups in both studies vs. none in the respective placebo groups. The most common AE across groups was nasopharyngitis.Oral tofacitinib demonstrated significant efficacy vs. placebo during the initial 16 weeks of treatment in patients with moderate-to-severe psoriasis. Safety findings were consistent with prior studies.
COPD and its impact on ability to continue to work
Authors: Monica Fletcher, Helen Albrow, Samantha Walker
Journal: European Respiratory Journal (2011)

Introduction: COPD affects large numbers of people of working age. This international study measured the personal, social and economic burden of disease in this population. The age, disease severity, and co-morbidity data are presented according to employment status, to identify the characteristics of individuals across the groups.

Method: 2426 respondents from Brazil, China, Germany, Turkey, UK, US were recruited utilising a mixed methods design. Employment status was recorded: currently employed, not working and retired due to COPD. Disease severity was assessed using MRC scores (Mild: 1-2, Mod 3-4, Severe 5).

Results: Retirees reported greater disease severity than workers (MRC m: 4.1 v 3.1, p<0.005), more co-morbidities (m: 2.5 v m: 1.1). More retirees reported anxiety and depression. 60% of retirees had mild or moderate disease v 91% in work. 64% (n 284) of early retirees retired over 4 years ago.

View this table:

Table 1. Demographic data of employed and non-employed groups





Conclusions: It is possible that disease severity limits ability to work, however the trigger to retire may also be due to other factors including co-morbidities. Workers registered the lowest prevalence of psychological disorders and it is unclear whether this is due to milder disease, age or employment status. This data suggests employers and occupational health professionals have a key role in keeping people with COPD in active work for longer.
Polycomb repressive complex 2 component Suz12 is required for hematopoietic stem cell function and lymphopoiesis
Authors: Stanley C. W. Lee, Sarah Miller, Craig Hyland, Maria Kauppi, Marion Lebois, Ladina Di Rago, Donald Metcalf, Sarah A. Kinkel, Emma C. Josefsson, Marnie E. Blewitt, Ian J. Majewski, Warren S. Alexander
Journal: Blood (2015)
LSC 2013 abstract - TLR-3 triggered aggravation of experimental asthma depends on IL-17
Authors: Lars Lunding, Christina Vock, Sina Webering, Christoph Hölscher, Heinz Fehrenbach, Michael Wegmann
Journal: European Respiratory Journal (2013)

The inflammatory phenotype of acute asthma exacerbations has been reported to be characterized by a heterogeneous infiltrate with eosinophils and large numbers of neutrophils in sputum as well as broncho-alveolar lavage (BAL). Epidemiological surveys suggested viral infection of the respiratory tract as the main trigger. Double stranded RNA is produced as an intermediate during replication of respiratory viruses and can be sensed by toll-like receptor 3 (TLR3). TLR3 could therefore play a key role in the pathogenesis of acute asthma exacerbation. Our study aimed at i) establishing a mouse model of TLR3 trigged asthma exacerbation and ii) clarifying the underlying mechanisms.  Intra-nasal (i.n.) application of the TLR3 ligand poly (I:C) induced an exacerbation of experimental allergic asthma in mice characterized by enhanced release of pro-inflammatory cytokines, mucus production, and pronounced airway hyperresponsiveness (AHR). Exacerbation included marked infiltration of neutrophils and T helper 17 (TH17) cells. . None of these characteristics could be observed in mice lacking IL-17A, indicating an essential role of this cytokine in mediating TLR3 triggered asthma exacerbation. Furthermore, in IL-23p19 mice, which lack IL-17 producing γδ T cells and TH17 cells, local application of poly (I:C) again provoked asthma exacerbation. Therefore, we suggest IL-17 producing NKT cells as main cell type involved in TLR3 triggered exacerbation of allergic asthma in mice.