tbuckley/cabot-search huggingface dataset:
Late Mortality Experience in Five-Year Survivors of Childhood and Adolescent Cancer: The Childhood Cancer Survivor Study
Authors: Ann C. Mertens, Yutaka Yasui, Joseph P. Neglia, John D. Potter, Mark E. Nesbit, Kathy Ruccione, W. Anthony Smithson, Leslie L. Robison
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Survivors of childhood and adolescent cancer are at risk for long-term effects of disease and treatment. The Childhood Cancer Survivor Study assessed overall and cause-specific mortality in a retrospective cohort of 20,227 5-year survivors. PATIENTS AND METHODS: Eligible subjects were individuals diagnosed with cancer (from 1970 to 1986) before the age of 21 who had survived 5 years from diagnosis. Underlying cause of death was obtained from death certificates and other sources and coded and categorized as recurrent disease, sequelae of cancer treatment, or non–cancer-related. Age and sex standardized mortality ratios (SMRs) were calculated using United States population mortality data. RESULTS: The cohort, including 208,947 person-years of follow-up, demonstrated a 10.8-fold excess in overall mortality (95% confidence interval, 10.3 to 11.3). Risk of death was statistically significantly higher in females (SMR = 18.2), individuals diagnosed with cancer before the age of 5 years (SMR = 14.0), and those with an initial diagnosis of leukemia (SMR = 15.5) or CNS tumor (SMR = 15.7). Recurrence of the original cancer was the leading cause of death among 5-year survivors, accounting for 67% of deaths. Statistically significant excess mortality rates were seen due to subsequent malignancies (SMR = 19.4), along with cardiac (SMR = 8.2), pulmonary (SMR = 9.2), and other causes (SMR = 3.3). Treatment-related associations were present for subsequent cancer mortality (radiation, alkylating agents, epipodophyllotoxins), cardiac mortality (chest irradiation, bleomycin), and other deaths (radiation, anthracyclines). No excess mortality was observed for external causes (SMR = 0.8). CONCLUSION: While recurrent disease remains a major contributor to late mortality in 5-year survivors of childhood cancer, significant excesses in mortality risk associated with treatment-related complications exist up to 25 years after the initial cancer diagnosis.
Calprotectin and IBD * Author's reply
Authors: M Lemann
Journal: Gut (2005)

Costa and colleagues ( Gut 2005; 54 :364–8) recently reported a study describing the ability of faecal calprotectin to predict relapse in the following year in patients with inflammatory bowel disease (IBD). They concluded that a calprotectin level >150 µg/g was predictive of relapse in Crohn’s disease (CD) and in ulcerative colitis (UC), but was more effective in predicting relapse in UC. Unfortunately, we believe that the authors failed to demonstrate these two points.

If faecal calprotectin >150 µg/g was clearly predictive of relapse in UC patients, this was not the case in CD (p = 0.07 and p = 0.31 for the likelihood ratio test in univariate and multivariate analyses, respectively). This may be due to the method used to determine the cut off value for calprotectin. Firstly, the receiver operating curve (ROC) method did not provide any cut off value for CD as the curve was not different from the diagonal and the confidence interval of the area under the curve included 0.5 (0.40–0.77). Secondly, the ROC curve method was not appropriate as it does not take into account the time to relapse, in contrast with the proportional hazards model used to test the predictive value of calprotectin. Classical methods related to time to relapse should have been preferred.1,2

The assertion, both in the title and in the text, that calprotectin was …
Health Behaviors and Quality of Life Among Colorectal Cancer Survivors
Authors: Elizabeth A. Rohan, Julie S. Townsend, Temeika L. Fairley, Sherri L. Stewart
Journal: Journal of the National Comprehensive Cancer Network (2015)

Purpose: To examine, at the population level, health behaviors, comorbidities, and health-related quality of life among colorectal cancer (CRC) survivors compared with other cancer survivors and persons without cancer. Methods: We used data from the 2009 and 2010 Behavioral Risk Factor Surveillance System cancer survivor modules. We calculated descriptive statistics, conducted chi-square tests for comparisons, and used multivariable logistic regression analysis to compare CRC survivors with other cancer survivors and persons without cancer. Results: Of the 52,788 cancer survivors included in this analysis, 4001 reported being CRC survivors. When compared with other cancer survivors, CRC survivors reported higher percentages of obesity and lack of physical activity; however, they had lower levels of current smoking. Adjusted results show that CRC survivors were significantly more likely to report lack of physical activity, fair/poor health, and other chronic health conditions compared with persons without a cancer diagnosis. Conversely, CRC survivors reported lower levels of current smoking than persons without cancer. Conclusions: CRC survivors have a higher proportion of heath conditions and behaviors that may significantly increase their risks for recurrence or development of a second cancer. Targeted interventions to address these health issues should be considered.
The Occurrence and Effects of Human Vitamin E Deficiency
Authors: Philip M. Farrell, John G. Bieri, Joseph F. Fratantoni, Robert E. Wood, Paul A. di Sant'Agnese
Journal: Journal of Clinical Investigation (1977)

The role of vitamin E in human nutrition was studied by investigation of patients with cystic fibrosis (CF) and associated pancreatic insufficiency. Vitamin E status was assessed by measurement of the plasma concentration of the principal circulating isomer, alpha-tocopherol. Results of such determinations in 52 CF patients with pancreatogenic steatorrhea revealed that all were deficient in the vitamin. The extent of decreased plasma tocopherol varied markedly but correlated with indices of intestinal malabsorption, such as the serum carotene concentration and percentage of dietary fat absorbed. Supplementation with 5-10 times the recommended daily allowance of vitamin E in a water-miscible form increased the plasma alpha-tocopherol concentrations to normal in all 19 CF patients so evaluated. Studies on the effects of vitamin E deficiency focused on possible hematologic alterations. An improved technique was developed to measure erythrocyte hemolysis in vitro in the presence of hydrogen peroxide. While erythrocyte suspensions from control subjects demonstrated resistance to hemolysis during a 3-h incubation, all samples from tocopherol-deficient CF patients showed abnormal oxidant susceptibility, evidenced by greater than 5% hemoglobin release. The degree of peroxide-induced hemolysis was related to the plasma alpha-tocopherol concentration in an inverse, sigmoidal manner. The possibility of in vivo hemolysis was assessed by measuring the survival of (51)Cr-labeled erythrocytes in 19 vitamin-E deficient patients. A moderate but statistically significant decrease in the mean (51)Cr erythrocyte half-life value was found in this group. Measurement of erythrocyte survival before and after supplementation of 6 patients with vitamin E demonstrated that the shortened erythrocyte lifespan could be corrected to normal with this treatment. Other hematologic indices in deficient subjects, however, were normal and did not change upon supplementation with vitamin E. It is concluded that CF is invariably associated with vitamin E deficiency, provided that the patient in question has pancreatic achylia and is not taking supplementary doses of tocopherol. Concomitant hematologic effects consistent with mild hemolysis, but not anemia, occur and may be reversed with vitamin E therapy. Patients with CF should be given daily doses of a water-miscible form of vitamin E to correct the deficiency.
Painful and Pruritic Papules in the Gray Shading of a Tattoo
Authors: Jennifer Brooks, Emily Behrens, Kyle Prickett
Journal: JAMA Dermatology (2015)

A woman presented with multiple painful, pruritic papules and pustules that developed 1 week after the addition of gray shading toa tattoo; results from a routine wound culture were negative for organisms. What is your diagnosis?
A new possibility of process monitoring in lung cancer: Volatile organic compounds detected with ion mobility spectrometry to follow the success of the therapeutic process
Authors: Julia Isabella Kurth, Kaid Darwiche, Jörg Ingo Baumbach, Lutz Freitag
Journal: European Respiratory Journal (2011)

Introduction:  Lung cancer is mostly detected when it is already too late for surgery. But even when tumours can still be operated, there has not been a simple, convenient way of observing any follow-up parameters such as PSA in prostate cancer. With the non-invasive analysis of Volatile Organic Compounds (VOCs) in exhaled breath using ion mobility spectrometry (IMS) we get the chance to step up in this development.   Objectives:  To develop a non-invasive technique of analysing new tumour markers in order to find a follow up biomarker for an improved monitoring of the treatment of lung cancer patients.   Methods:  Exhaled breath from 33 lung cancer patients was collected and analysed with an IMS device before and after lung surgery. The patients were split into groups according to the tumour histology. Additional conditions such as COPD, medication and former radiation or chemotherapy were also taken into consideration. Furthermore, the results were statistically analysed.   Results:  There were several peaks which showed differences between the pre- and post-surgery groups (such as “EV” normU: 0,062 in squamous cell carcinoma). Further results will be presented in box plots.   Conclusion:  As the results show differences between the peaks before and after surgery, the analysis of VOCs in exhaled air might be a new non-invasive possibility of monitoring the process of lung cancer therapy.  In future research it would be interesting to carry out further investigations on long-term patient observations after defined time intervals.
A study of fadrozole, a new aromatase inhibitor, in postmenopausal women with advanced metastatic breast cancer.
Authors: J I Raats, G Falkson, H C Falkson
Journal: Journal of Clinical Oncology (1992)

PURPOSE The study investigated the therapeutic effects of fadrozole (CGS 16949A), a new aromatase inhibitor, in women who had received prior treatment for metastatic breast cancer. MATERIALS AND METHODS Eighty postmenopausal women who had received prior treatment for metastatic breast cancer were randomized to receive fadrozole 1 mg/d or 4 mg/d per day orally. Seventy-eight patients were assessable for toxicity and response. RESULTS Toxicity was limited to mild (grade 1) to moderate (grade 2) hot flashes in 28%, nausea and vomiting in 13%, fatigue in 8%, and mild loss of appetite in 5% of patients. No electrolyte or unanticipated hormonal changes occurred. The overall response was 23% (complete response, 10%; partial response, 13%). In addition, 45% of the patients had a no change status. There was no difference in response rate between the patients randomized to the two different doses of fadrozole. Only dominant site of metastases significantly affected response. The median time to treatment failure (TTF) was 4.4 months (4.7 months on 1 mg/d and 3.7 months on 4 mg/d). The median survival was 22.6 months (17.5 months on 1 mg/d; median survival has not been reached in patients on 4 mg/d). The response and survival in patients with estrogen receptor (ER)-positive and ER-unknown disease were not significantly different. CONCLUSIONS Fadrozole has good therapeutic effect as a second-line treatment in postmenopausal women with metastatic breast cancer. In this study there was no significant difference in toxicity or response between 1 mg/d and 4 mg/d. Further trials comparing fadrozole to other hormone treatment are indicated.
Monitoring PGD2 production in airway disease
Authors: Johan Larsson, David Balgoma, Ingrid Delin, Theo Gülen, Gunnar Nilsson, Hans Hägglund, Kameran Daham, John Lawson, Garret FitzGerald, Barbro Dahlén, Craig Wheelock, Sven-Erik Dahlén
Journal: European Respiratory Journal (2011)

Introduction: Prostaglandin (PG) D2 is a major mast cell mediator implicated in asthma and airway disease. Measurement of the urinary levels of 9α,11β-PGF2 has been established to monitor PGD2 production. Tetranor prostaglandin D (PGDM) is however the major urinary metabolite of PGD2.

Aims and objectives: To evaluate the use of urinary levels of 9α,11β-PGF2 vs. PGDM. In addition, the use of enzyme immune assay (EIA) was compared with LC-MS/MS.

Methods: Urinary samples from four studies were used; bronchoprovocation using allergen (n=9) and aspirin in aspirin-intolerant asthma (n=11), effect of celecoxib on baseline excretion (n=19), and excretion in patients with mastocytosis or anaphylaxis (M/A) during exacerbation (n=15). Urinary excretion of 9α,11β-PGF2 and PGDM were measured by specific EIAs (Cayman Chemical) and LC-MS/MS, and data expressed as ng/mmol creatinine.

Results: The levels of PGDM (mean±SEM) before allergen challenge were 1330±348 and 1236±192 after (p>0.05), the corresponding values of 9α,11β-PGF2 were 40±4 and 77±10 (p=0.002), respectively.

With aspirin challenge levels of PGDM were 516±82 before and 609±95 after (p>0.05), whereas the levels of 9α,11β-PGF2 were 56±16 and 75±24 (p=0.002), respectively.

In M/A the levels of PGDM and 9α,11β-PGF2 were 1977±886 (p<0.05 for PGDM vs baseline in healthy subjects) and 251±66 respectively, with values mildly correlated (r=0.698, p=0.00382).

Bland-Altman analysis showed good agreement between PGDM measurements with MS and EIA.

Conclusion: The earlier metabolite 9α,11β-PGF2 may be more suitable to follow the dynamics of release during challenges whereas the higher levels of PGDM may be more appropriate for monitoring global differences in baseline production of PGD2.
microRNA levels in nasal biopsies in allergic and non-allergic rhinitis and asthma
Authors: Hille Suojalehto, Marja-Leena Majuri, Elina Toskala, Maritta Kilpeläinen, Harri Alenius
Journal: European Respiratory Journal (2011)

Introduction:  Rhinitis and bronchial asthma are both manifestations of an inflammatory process within a continuous airway system. The upper and lower airways may be considered as a unique entity influenced by a common and often evolving inflammation process.   Aims and objectives:  We aimed to study if microRNA (miRNA) and nasal nitric oxide (nNO) levels differentiate in asthma, allergic rhinitis (AR) and non-allergic rhinitis (NAR) patients.   Methods:  A 12-years follow-up survey on factors for asthma and atopic diseases was conducted with 6041 subjects aged 30-38 years in year 2007. From them 180 responders were selected to participate in the clinical study, when nNO and nasal biopsies were taken. Based on the survey and clinical data the participants were classified to healthy controls (n=40), AR (n=51), AR combined with asthma (AR+asthma n=37) and NAR (n=42) patients. The levels of 27 inflammatory miRNAs were determined from nasal biopsies.   Results:  No significant changes in the levels of 24 miRNAs were observed between groups. However, expression of mir-146a was significantly elevated in AR and AR+asthma groups compared to controls. In addition, the levels of mir-126 were significantly up-regulated in AR+asthma group compared to controls. Similarly, mir-18a levels were increased in AR+asthma group compared to controls and NAR group. Finally, nNo levels were significantly increased in AR and AR+asthma group compared to control or NAR group.   Conclusions:  These preliminary findings emphasizes that some differences in the miRNA levels can be found from the upper airways between these patient groups. Further studies are needed to deeper examine the molecular mechanisms and to establish new markers for the diseases.
Preservation of vascular access.
Authors: J L Porile, M Richter
Journal: Journal of the American Society of Nephrology (1993)

Preservation of vascular access is critical in the long-term successful management of hemodialysis patients. Dialysis access abnormalities are the most common cause of hospitalization in this patient group, and access problems can increase the morbidity and cost involved in the care of these patients. Native fistulas are preferable to synthetic grafts because of longer survival and a lower complication rate. Venous outflow stenosis is the most common site of obstruction in a failing graft. The pathophysiology of access failure is poorly understood, but it seems to be related to intimal hyperplasia in the native vessel downstream from the anastomosis. The stimulation of local growth factors by needle puncture may also play a role. An assessment of access adequacy includes careful physical examination, laboratory evaluation, and ultimately, angiography. Measurements of recirculation and venous pressure are commonly used to screen for access dysfunction, and their appropriate use will lower the incidence of graft loss in dialysis units. Treatment is usually either angioplasty or surgery, with some centers having success with thrombolytic therapy. New techniques such as atherectomy and stent placement may prove to be beneficial, but this requires further study.
NIH Awards $35 Million in Natural Products Research Grants
Authors: Julie A. Jacob
Journal: JAMA (2015)

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Allergic inflammatory cells use different GATA factors to activate CCR3 transcription
Authors: Soo Kang Kong, Il Yup Chung
Journal: European Respiratory Journal (2012)

CCR3 is a chemokine receptor initially thought specific to eosinophils but subsequently identified on Th2 cell subsets and mast cells. The prominent allergic inflammatory cells, eosinophils, mast cells, and Th2 cells exhibit preferential expression of GATA-1, GATA-2, and GATA-3, respectively. We have previously demonstrated GATA-1-mediated CCR3 transcription with functional mapping of a GATA element in the regulatory region of CCR3 gene. Here, we investigated whether GATA factors other than GATA-1 play a major role in CCR3 transcription in these cell types. Knockdown assay showed that GATA-2 siRNA reduced the CCR3 reporter activity in EoL-1 eosinophilic cells, and GATA-1 and GATA-2 siRNAs reduced in EoL-1 and HMC-1 mast cells, while GATA-3 siRNA suppressed it in Jurkat T cells. In parallel, EMSA and ChIP analyses revealed DNA binding to and occupancy on the functional GATA element of different GATA factors. These results highlight that different GATA factors participate in CCR3 transcription in a cell type-speciifc fashion among the major allergic inflammatory cells.
Breathing retraining as a treatment modality for dysfunctional breathing in children
Authors: Nicki Barker, Mark Everard
Journal: European Respiratory Journal (2014)

Background   Dysfunctional breathing (DB) is a cause of significant morbidity in children. Physiotherapists currently treat the condition using breathing retraining but there is no evidence regarding the efficacy of this intervention (1).   Aim   The aim of this study was to investigate whether breathing retaining can improve clinical outcomes and quality of life in children with DB and whether those improvements are maintained.   Methods   34 children aged 7-16 years, referred to a specialist clinic with a diagnosis of DB, received breathing retraining from an experienced respiratory physiotherapist. The children and their families completed questionnaires on symptoms (using the Nijmegen questionnaire) and quality of life (using the PedsQL) prior to starting the intervention (time point 1), at completion of the intervention (time point 2) and 6 months after the completion of the intervention (time point 3).   Results   A significant difference was found in all measures between time points 1 and 2 (pl0.0001) with symptom score decreasing and quality of life (both child and parent reported) increasing. No significant difference was seen in scores between time points 2 and time points 3 (pg0.05) indicating that improvements made in both domains were maintained 6 months following completion of the intervention.   Conclusion   Breathing retraining offers positive benefits in terms of symptoms and quality of life to children with DB, both immediately following the completion of the intervention and up to at least six months later.  1. Barker NJ, Everard ML. Getting to grips with 9dysfunctional breathing9. Pediatr Respir Rev 2014; In Press.
Recruitment and phenotypic characteristics of interleukin 9–Producing CD4+ T cells in malignant pleural effusion
Authors: Xiaoning Bu, Qiong Zhou, Jian-chu Zhang, Zhi-jian Ye, Zhao-hui Tong, Huan-zhong Shi
Journal: European Respiratory Journal (2013)

Background and objective:   Our previous data have demonstrated that numbers of IL-9–producing CD4 +  T cells (Th9 cells) in malignant pleural effusion (MPE) were significantly increased when compared with blood. The aim of the present study was to investigate the mechanism by which Th9 cells were recruited into MPE and the phenotypic characteristics of pleural Th9 cells.    Methods:   The expression patterns of chemokine receptors (CCRs) on Th9 cells and the chemoattractant activity of chemokine CCL20 for Th9 cells  in vitro  were observed. The phenotypic features of Th9 cells in MPE were determined by flow cytometry.    Results:   We found that Th9 cells in both MPE and blood expressed high level of CCR6 on their surface. An  in vitro  migration assay confirmed that both MPE and supernatants of cultured pleural mesothelial cells could induced the migration of Th9 cells, and anti−CCL20 mAb significantly inhibited the ability of MPE or supernatants to stimulate Th9 cell chemotaxis. We also noted that pleural Th9 cells expressed high levels of CD45RO and very low levels of CD45RA and CD62L, displaying the phenotype of effector memory cells.    Conclusions:   Our data revealed that recruitment of Th9 cells into MPE could be induced by pleural CCL20, and that majority of Th9 cells in MPE displayed the phenotype of effector memory cells.