tbuckley/cabot-search huggingface dataset:
Surrogate endpoints in neoadjuvant rectal cancer trials: Statistical evaluation using data from the FFCD 9203 trial
Authors: N. Methy, L. Bedenne, J. Gérard, T. Conroy, O. Bouché, O. Chapet, M. Ducreux, F. Bonnetain
Journal: Journal of Clinical Oncology (2008)

4086 Background: Neo-adjuvant rectal cancer trials use overall survival (OS) and local control as standard endpoints. Using earlier endpoints as primary outcomes in phase III trials requires them to be validated as surrogates for OS or local control. The aim of this study was to evaluate the statistical validity of specimen sterilization, pT and pN stages and circumferential resection margin as surrogate endpoints for OS and local recurrence free survival (LRFS). Methods: We used data from the FFCD 9203 trial (Gérard et al. J Clin Oncol 2006): preoperative radiotherapy (RT) vs preoperative chemoradiation (CT-RT) in T3–4 rectal cancers. Based on logistic regressions and Cox proportional hazards regression models we applied single-trial validation methods: Prentice criteria, proportion of treatment effect explained (PTE), relative effect, adjusted association and the proportion of variation explained (R²). OS was defined as time interval between randomization and death (all causes) and LRFS as time interval between randomization and local recurrence. Survival curves were estimated using Kaplan-Meier method and compared using Log-Rank tests. Results: Our analyses were based on the 742 eligible patients of the trial (367 patients in the RT arm and 375 in the CT-RT arm). Complete sterilization of the operative specimen was more frequent in the CT-RT arm (11.4% vs 3.6%, p<.0001) and the 5-year local recurrence rate was significantly lower (16.5% vs 8.1%, p=0.004) while the 5-year OS did not differ (67.9% vs 67.4%, p=0.69). None of the variables fulfilled the four Prentice criteria whatever final endpoint. The most surrogate variable was specimen sterilization categorized as pT0 or few residual cells (S1) vs evolutive residual cells (S0). It explained 12% of the effect of treatment on LRFS (PTE=0.119) but the lower bound of the 95% CI was under the critical limit of 0.5. After adjusting for treatment, relative risk of local recurrence (S1 vs S0) was 0.56 (95% CI [0.28–1.10], p=0.09, R²=0.05). With OS as final endpoint, PTE for sterilization was not interpretable (PTE=-249.3%). Conclusions: Our data did not allow validating relevant surrogates for long term outcomes in neo- adjuvant rectal cancer trials. To increase power, an individual meta-analysis is planned. No significant financial relationships to disclose.
Tuberculous mycotic aneurysm of aorta: A rare complication
Authors: Parameswari Rekha, Parackal Sukumaran, T.K Jayakumar, Kummannoor Venugopal
Journal: European Respiratory Journal (2011)

39 year old male was started on antituberculous treatment based on symptoms and miliary shadows on chest x-ray. 2 months later he had persistent abdominal pain. Abdominal examination revealed a pulsatile palpable mass with brui. Ultrasound &CT abdomen confirmed aneurysmal dilatation of aorta from hiatus to bifurcation with infra renal involvement. No leak or dissection.  Surgical exploration revealed aneurysm with areas of impending rupture, clots & caseous material. Endoaneurysmal graft repair surgery was done. Clot was teeming with AFB. Postoperatively patient had paraplegia due to ischemic myelopathy.  Tuberculous mycotic aneurysm of aorta is a rare complication with poor prognosis. Less than 50 cases have been reported. Combined medical & surgical therapy is advised.
Abstract 3874: Loss of DDB2 enhances the tumorigenicity of ovarian cancer cells through expanding cancer stem-like cell population
Authors: Chunhua Han, Ran Zhao, Xingluo Liu, Amit Kumar Srivastava, Li Gong, Hsiaoyin Mao, Meihua Qu, Weiqiang Zhao, Jianhua Yu, Qi-En Wang
Journal: Cancer Research (2014)

Abstract Ovarian cancer is an extremely aggressive disease associated with a high percentage of recurrence and chemotherapy resistance. DNA damage binding protein 2 (DDB2) is a 48-kDa protein originally identified as a component of the damage-specific DNA-binding heterodimeric complex DDB. Besides the known ability of DDB2 protein to bind ultraviolet (UV)-damaged DNA and serving as the initial damage recognition factor during nucleotide excision repair (NER), DDB2 was also reported to be involved in the promotion of apoptosis to reduce cisplatin resistance of ovarian cancer cells, control of cell migration, invasiveness and breast tumor progression, as well as suppression of metastasis of colon cancer through a transcriptional regulatory mechanism. Here we show that DDB2 is downregulated in human ovarian serous adenocarcinomas. DDB2 overexpression in human ovarian cancer cell line CP70 suppressed its capability to recapitulate tumors in athymic nude mice, as well as the growth of these cells cultured in semisolid media. Flow cytometry analyses indicate that DDB2 overexpression in CP70 cells reduced the abundance of ALDH+ cells, which are believed to be cancer stem-like cells (CSCs) in ovarian cancer. In contrast, downregulation of DDB2 in ovarian cancer cell line A2780 increased the percentage of ALDH+ cells. In addition, we analyzed the expression level of DDB2 in the putative CSCs isolated from various ovarian cancer cell lines, and demonstrated that DDB2 expression is downregulated in all tested CSCs in comparison with their parental bulk tumor cells. Overexpression of DDB2 in the ovarian CSCs reduced the expression of CSC marker Nanog, as well as inhibited the self-renewal of these CSCs. In addition, overexpression of DDB2 in CSCs isolated from ovarian cancer cell line SKOV-3 also decreased the tumorigenicity of these cells in NOD/SCID mice. Further analysis of publicly available gene expression array datasets revealed that low DDB2 expression correlates with poor outcomes among ovarian cancer patients, suggesting that loss of DDB2 may promote ovarian tumor relapse through expanding CSC population. Given that the DDB2 protein level is downregulated in ovarian tumor cells, targeting DDB2 expression could be a promising strategy to eradicate CSCs, and helps to halt ovarian cancer relapse. (Supported by NIH R01 grant CA151248 to QEW) Citation Format: Chunhua Han, Ran Zhao, Xingluo Liu, Amit Kumar Srivastava, Li Gong, Hsiaoyin Mao, Meihua Qu, Weiqiang Zhao, Jianhua Yu, Qi-En Wang. Loss of DDB2 enhances the tumorigenicity of ovarian cancer cells through expanding cancer stem-like cell population. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3874. doi:10.1158/1538-7445.AM2014-3874
A retrospective clinical and radiological review of 20 Castleman's disease cases
Authors: Yasunori Ichimura, Jiro Terada, Yusuke Naito, Tetsuo Fujita, Takashi Urushibara, Ayako Shigeta, Takayuki Sakurai, Ken Iesato, Fuminobu Kuroda, Yuji Tada, Seiichiro Sakao, Katsushi Kurosu, Yasunori Kasahara, Nobuhiro Tanabe, Yuichi Takiguchi, Koichiro Terada
Journal: European Respiratory Journal (2012)

[RATIONALE] Castleman9s disease is one of the rare lymph proliferative diseases, which usually involves lung. There is still no established standard therapy at the moment. We have examined the clinical findings including therapies and prognoses. [METHODS] On the cases of Castleman9s disease consulted in our hospital in the past 10 years until 2011, we retrospectively examined based on the medical records. [RESULTS] The study comprised 20 patients (70% male) with a mean age of 55 (25-70) years old. As complications, 6 cases had POEMS syndrome (2 with PH), 3 had hematologic diseases (DLBCL, ITP, MDS). By chest CT, mediastinal adenopathy was confirmed in all cases, 10 were confirmed with lung involvement (5: nodular shadow; 2: reticulonodular shadow; 4: GGO; 5: interlobular septal thickening), 6 with pleural effusion, and 3 with cardiac effusion. The diagnostic methods were 13 cases of surgical lymph node biopsy, 6 cases of lung biopsy (2: TBLB; 2: VATS lung biopsy; 1: open lung biopsy; 1: CT-guided lung biopsy), 1 case of lachrymal gland biopsy. Histopathologically, there were 4 cases of hyaline vascular type and 16 cases of plasma cell type. 4 cases were prioritized on the treatment for complications (3: POEMS syndrome; 1: ITP), and 2 were left untreated for a follow-up. Treatment was started for 14 cases using PSL at the time of diagnosis or exacerbation of symptom. [CONCLUSIONS] In this study, lung biopsies are useful as diagnostic method in the cases with pulmonary involvement. Few cases were confirmed with reduction of lymph node and improvement of lung involvement by treatment. But in many cases symptomatic improvement or suppression of the progress of the disease by the treatment were observed.
Comparison of life quality between patients with COPD and victims of chemical warfare using CAT (COPD assessment test) questionnaire
Authors: Abbas Fadaii, Fateme Hamidiimani, Bahador Bagheri, Bahar Taherkhanchi
Journal: European Respiratory Journal (2012)

Introduction

In COPD, measurement of health-related quality of life is a descriptive tool to estimate prognosis of the disease. Victims of chemical warfare who have small air way involvement are considered as a group of patients with COPD, yet in comparison with COPD patients who are smokers they have differences in severity of signs and symptom. The purpose of our work was to compare life quality in two groups of COPD patients using CAT questionnaire.

Materials and methods

The first group was composed of 40 patients who were smokers for at least 20 years. The second group was made of 45 patients who were victims of chemical warfare. They were not smokers. Both groups were male and both groups had obstructive pattern in spirometry (minimum criterion FEV1/FVC < 70%). Patients baseline characteristics and spirometry volumes were recorded and then subjects filled the CAT questionnaire.

Results

In group A, CAT scores varied from 2 to 34, mean= 19.25. FEV1 varied from 17% to 67%, mean= 33.14, and FVC ranged from 36.9% to80%, mean=51.14. In group B CAT scores varied from 5 to 39, mean= 22.25. FEV1 varied from 17.5% to 89%, mean= 53.14, and FVC ranged from 22.9% to100%, mean=61.12. Victims of chemical warfare in spite of significantly higher mean of respiratory volumes, had higher CAT total score.

Conclusion

In conclusion we can say although victims of chemical warfare with small airway disease have higher respiratory volumes, their quality of life is lower then other COPD patients.
Standard therapy increases the sensitivity of peripheral blood lymphocytes to glucocorticoids in cystic fibrosis but not in severe asthma
Authors: Alexander Pukhalsky, Galina Shmarina, Tamara Vylegzhanina, Tamara Chervinskaya, Olga Kozyreva, Nikolai Kapranov, Vladimir Alioshkin
Journal: European Respiratory Journal (2011)

Usually the asthma symptoms are well controlled with inhaled glucocorticoids (GCs) or β 2 -agonists, but a minority of patients continue to have uncontrolled asthma despite taking high doses of inhaled GCs, sometimes together with oral GCs. It is known that inflammatory response in such patients is relatively resistant to suppression. The aim of this study was to evaluate peripheral blood lymphocyte (PBL) sensitivity to antiproliferative effect of GCs in cystic fibrosis (CF) and asthmatic patients in the course of exacerbation treatment. Individual susceptibility of PBL to GCs was evaluated by Δ h  value calculation: an integrative parameter, including the level of mitogen-induced lymphocyte proliferation and inhibition degree of such stimulation by dexamethasone. In healthy subjects the mean Δ h  level was -0.24±0.30. Negative values of Δ h  correspond to high cell sensitivity to GC. CF patients with lung exacerbations demonstrated low cell sensitivity to GCs (Δ h  = 0.36±0.23), but after antibiotic treatment the sensitivity significantly increased (Δ h  = -0.54±0.24; p=0.014). On the contrary, the cell sensitivity of asthmatic patients remained extremely low. The therapy did not affect high Δ h  level, which averaged before and after exacerbation treatment 2.67±0.27 and 2.65±0.31, respectively. In conclusion, patients with severe asthma have stably diminished GC sensitivity of PBL when compared with CF patients and healthy subjects. We believe that such resistance is a consequence of GC treatment during a long period of time and may be associated with both immune cell selection and epigenetic changes of GC receptors.
Epidemiology of Mouth Cancer in 1989: A Review
Authors: P Boyle, G J Macfarlane, P Maisonneuve, T Zheng, C Scully, B Tedesco
Journal: Journal of the Royal Society of Medicine (1990)

The oral cavity and pharynx combined is the sixth commonest site of cancer in both sexes. In many countries the mortality rate is increasing among younger men born since approximately 1910-1920. A causal role in the aetiology of mouth cancer has been established for tobacco use, both smoking and chewing, separately and in conjunction with betel-quid chewing; with alcohol consumption and, less certainly, with other factors such as poor oral hygiene, nutritional factors and certain occupational exposures. In Western countries, there is convincing evidence that a large attributable risk can be ascribed to the joint habits of cigarette smoking and alcohol consumption. In Asian societies, a high attributable risk can be ascribed to cigarette smoking and betel chewing. Mouth cancer is at the same time an important form of cancer, and one for which practical prospects for prevention already exist. Against this background of a continually increasing trend among younger persons, it seems essential to engage upon programmes of prevention, including increasing awareness for early detection, against mouth cancer at the present time.
Indoleamine 2,3-dioxygenase (IDO) expression and malignant transformation in prostate cancer
Authors: M. Provenzano, C. Feder-Mengus, S. Wyler, T. Hudolin, R. Ruszat, W. P. Weber, T. Sulser, A. Bachmann, M. Heberer, G. C. Spagnoli
Journal: Journal of Clinical Oncology (2008)

5149 Introduction: A number of immunosuppressive factors have been suggested to play a role in functional impairment of the immune system in prostate cancer (PCA) patients. Among all, indoleamine 2,3-dioxygenase (IDO) has been considered to favour tumoral immune escape based on tryptophan degradation. We evaluated and compared the expression of genes encoding potential immunosuppressive factors such as IDO, ARG II and IL23 in human benign prostatic hyperplasia (BPH) and PCA also according to alpha-methylacyl-CoA racemace (AMACR) gene expression and kynurenine/tryptophan ratios. Furthermore, impairments of CD4+ and CD8+ T cells proliferation upon homeostatic cytokines (IL-2, IL-7, IL-15) stimulation was also quantified. Methods: 40 BPH and 36 PCA patients were enrolled upon informed consent. Quantitative RT-PCR was used to determine gene fold increases of immunosuppressive factors suggested to play a role for immune functional impairment in PCA. Peripheral blood mononuclear cells from same BPH and PCA patients or healthy donors were used for proliferative assays upon homeostatic cytokines stimulation. IDO protein expression was evaluated by immunohistochemistry. Tryptophan and its catabolites concentrations were evaluated in serum patients by HPLC. Statistic was performed using SPSS software package. Results: IDO gene expression significantly correlated with both histological malignancy (p=0.004) and AMACR (p=0.001) accounting for almost 5% of tumor cells (IDOhigh). Interestingly, IDOhigh gene expression was also correlating to serum kynurenine/tryptophan ratio (p=0.021). In contrast, ARG II, IL23, iNOS, eNOS genes were not significantly more expressed in PCA, as compared to BPH, while IL-17 expression was not modified. IL-6 gene expression was significantly (p=0.0002) enhanced while TGFb gene expression was significantly (p=0.035) decreased in PCA. Unfortunately, we could not find a significant reduction of T cells proliferation under homeostatic cytokine stimuli. Conclusion: IDO gene expression, frequently detectable in PCA and correlated with AMACR expression, appears to qualify as a marker of malignant transformation in prostate cancers. Further research is warranted to clarify its consequences on immune responsiveness in PCA patients. No significant financial relationships to disclose.
Inter-device variation in dual oximetry for polysomnography
Authors: Patrick Jamieson, Paul Burns
Journal: European Respiratory Journal (2012)

Aims 

Some sleep laboratories use two SpO2 channels to better detect artefact. This study aimed to examine the agreement between two SpO2 monitors used concurrently on the same polysomnography (PSG).

Methods 

117 PSGs were audited for this study. The PSGs included channels from an integrated SpO2 monitor (Nonin) and an external device from another manufacturer (Masimo). The mean SpO2 and the desaturation index (DI) for both oximeters were compared. Comparisons were made using Bland Altman analysis, with limits of agreement (LOA) of 1.96 standard deviations, and confidence intervals (CI) of 95%.

Results 

Bland Altman analysis indicated a bias of +1.7% (CI +1.4%, +2.0%), showing a systematic offset towards Masimo. The LOA were -1.2% (CI -1.7%, -0.7%) to 4.5% (CI 4.0%, 5.0%), indicating a variation of ±2.85%.

Bland Altman analysis of the DI indicates a -38.5% (CI: -28.0%, -49.1%) smaller DI for the integrated sensor as compared to the external sensor.

Conclusions 

When used to assess mean SpO2 there is a variation of ±2.9%, this may not be clinically acceptable. Additionally the external sensors produced systematically higher readings than integrated sensor. Therefore the outcome of an assessment of hypoxia is device dependant, if only one of these devices is used.

There is poor agreement between devices with regards to the desaturation index. The integrated sensor detected 38.5% less desaturations compared with the external sensor. This systematic bias suggests that an assessment of sleep disordered breathing is device dependant.
Subcutaneous allergen specific immunotherapy and immunological response in patients with bronchial asthma and allergic rhinitis in India
Authors: Nitesh Gupta, Raj Kumar, Juhi Mittal
Journal: European Respiratory Journal (2014)

Background : Subcutaneous allergen specific immunotherapy (SCIT) in bronchial asthma (BA) and allergic rhinitis (AR) acts by influencing basic immunological mechanisms, driven by production of cytokines like IL-5 among others.   Aim and Objective : The aim is to evaluate the response of immunotherapy against commonly implicated aero-allergns in India as measured by levels of inflammatory markers (IL-5, IL-6).   Method : 29 patients (18-48 yrs; 16 males) diagnosed with BA and AR underwent skin prick test for evaluation of allergic sensitivity. The patients were classified and treated as per GINA and ARIA guidelines and immunotherapy was initiated as per the standard Indian guidelines. Symptom score, medication requirement, Il-5 and Il-6 levels were obtained at 0, 3 and 6 months. Statistical analysis was done using Friedman test.   Results : The various antigens positive on SPT were mosquito, housefly, female cockroach, male cockroach, moth, rice weevil, house dust mite, cassia and prosis. SCIT was initiated against single antigen in 3 cases, two antigens in 6 cases, three antigens in 5 cases, four antigens in 8 cases and maximum of five antigens in 7 cases. The inflammatory markers, IL-5 and IL-6, for 0, 3 and 6 months were compared and it was observed that as the duration of treatment increases the levels significantly decreases (p=0.003). Also, significant reduction in symptoms and medication requirement was observed. There was no statistically significant difference in the mean response of SCIT against ≤2 or >2 antigens.   Conclusion : Mono and poly antigen SCIT is effective in suppressing inflammatory response in Indian patients.
Prognostic impact and implications of extracapsular lymph node involvement in colorectal cancer: a systematic review with meta-analysis
Authors: N Veronese, A Nottegar, A Pea, M Solmi, B Stubbs, P Capelli, G Sergi, E Manzato, M Fassan, L D Wood, A Scarpa, C Luchini
Journal: Annals of Oncology (2015)
Maximum voluntary ventilation is a better correlate of energy expenditure during simple activities of daily living than measures of airflow obstruction or respiratory muscle strength in patients with COPD
Authors: Vinícius Cavalheri, Kylie Hill, Leila Donária, Carlos Augusto Camillo, Fabio Pitta
Journal: European Respiratory Journal (2012)

Background: In patients with chronic obstructive pulmonary disease (COPD), the relationship between energy expenditure (EE) and measures of lung function has attracted attention. Weak to moderate associations were demonstrated between daily EE and measures of respiratory muscle strength, maximal voluntary ventilation (MVV), inspiratory capacity (IC) and forced expiratory volume in one second (FEV1) in patients with moderate to severe disease. However, as this earlier work measured EE over a 12-hour period, it is unclear to what extent the EE elicited during individual and simple activities of daily living were associated with these measures of lung function. Objective: To explore the extent to which energy expenditure (EE) elicited during individual and simple activities of daily living is associated with different measures of lung function in patients with COPD. Methods: Thirty-six patients (20 males; FEV1 48±15%predicted; body mass index 25.7± 8 kg·m-2) underwent assessment of lung function followed by measures of indirect calorimetry whilst performing five simple activities of daily living (modified from the Glittre-test). Results: MVV was the only parameter of lung function associated with EE elicited during each activity of daily living as well as with the total EE over the 5 tasks (0.39
Geographical Studies on Rheumatoid Arthritis
Authors: J. S. Lawrence, T. Behrend, P. H. Bennett, J. M. Bremner, T. A. Burch, J. Gofton, W. O'Brien, H. Robinson
Journal: Annals of the Rheumatic Diseases (1966)

Though it has been suggested that rheumatoid arthritis (RA) is influenced by climate and is less frequent in tropical climates, no reliable evidence has so far been forthcoming to confirm or refute this.The prevalence of the disease is known to increase with age, and it would, therefore, be expected that it would be less frequent in populations with a low life expectancy.In surveys of population samples aged 55 to 64 years in a number ofNorthern European countries, de Graaff, Laine, and Lawrence (1963) found no relationship to latitude; but since the range of latitude amounted to only 100, these surveys could not exclude such a relationship.In a comparison of the same age group in populations in Leigh, England, and Pittsburgh, U.S.A., Cobb and Law- rence (1957) observed a rather lower prevalence in the latter.Sitaj, Niepel, Kostka, Trnavsky, and Sipos (1964) similarly found a lower prevalence in a rural sample in the region of Pie'sany, Southern Czecho- slovakia, than in the Northern European surveys.On the other hand, Bunim, Burch, and O'Brien (1964) found no significant difference between the .1,
Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1
Authors: Ruth Wassermann, Muhammet F. Gulen, Claudia Sala, Sonia Garcia Perin, Ye Lou, Jan Rybniker, Jonathan L. Schmid-Burgk, Tobias Schmidt, Veit Hornung, Stewart T. Cole, Andrea Ablasser
Journal: Cell Host & Microbe (2015)