Pitfalls of predicting complex traits from SNPs

The success of genome-wide association studies (GWASs) has led to increasing interest in making predictions of complex trait phenotypes, including disease, from genotype data. Rigorous assessment of the value of predictors is crucial before implementation. Here we discuss some of the limitations and pitfalls of prediction analysis and show how naive implementations can lead to severe bias and misinterpretation of results

Is albumin gradient or fluid to serum albumin ratio better than the pleural fluid lactate dehydroginase in the diagnostic of separation of pleural effusion?

BACKGROUND: To determine the accuracy of serum-effusion albumin gradient (SEAG) and pleural fluid to serum albumin ratio (ALBR) in the diagnostic separation of pleural effusion into transudate and exudate and to compare SEAG and ALBR with pleural fluid LDH (FLDH) the most widely used test. METHODS: Data collected from 200 consecutive patients with a known cause of pleural effusion in a United Kingdom district general hospital. RESULTS: The median and inter quartile ranges (IQR) for SEAG 93.5 (33.8 to 122.5) g/dl, ALBR 0.49 (0.42 to 0.62) and FLDH 98.5 IU/L(76.8 to 127.5) in transudates were significantly lower than the corresponding values for exudates 308.5 (171 to 692), 0.77 (0.63 to 0.85), 344 (216 to 695) all p < 0.0001. The Area Under the Curve (AUC) with 95% confidence intervals (Cl) for SEAG, ALBR and FLDH were 0.81 (0.75 to 0.87), 0.79 (0.72 to 0.86) and 0.9 (0.87 to 0.96) respectively. The positive likelihood ratios with 95%CI for FLDH, SEAG, and ALBR were: 7.3(3.5–17), 6.3(3–15) 6.2(3–14) respectively. There was a significant negative correlation between SEAG and ALBR (r= -0.89, p < 0.0001). CONCLUSION: The discriminative value for SEAG and ALBR appears to be similar in the diagnostic separation of transudates and exudates. FLDH is a superior test compared to SEAG and ALBR

Chemotherapy-Induced Neuronal Maturation in Sinonasal Teratocarcinosarcoma—a Unique Observation

Sinonasal teratocarcinosarcoma (SNTCS) is a rare and highly malignant tumour with combined features of a teratoma and carcinosarcoma. We report the first case of a SNTCS in 23 year old male treated with neo-adjuvant chemotherapy followed by cranio-facial resection. The resection specimen displayed cellular maturation in the neuroectodermal component. The patient presented with a short history of nasal obstruction, epistaxis and headache. On imaging, a bone destroying lesion of left paranasal sinuses and nasal cavity was identified. The diagnosis of SNTCS could be offered only on the third biopsy which showed heterogeneous admixture of primitive neuroectodermal, epithelial and mesenchymal elements. An adequate sampling with high index of suspicion is needed to catch hold this rare tumor. Tumor was excised after 4 cycles of neo-adjuvant chemotherapy. On microscopic examination, it showed similar epithelial and mesenchymal components as the pretreatment biopsies. However, the primitive neuroectodermal component displayed extensive neuronal maturation. The undifferentiated neuroectodermal cells were completely absent in the post chemotherapy specimen. This case throws light on the morphologic evidence of chemotherapy induced maturation in the neuroectodermal component within SNTCS, an event hitherto not reported in the literature in case of SNTCS

Does pleural fluid appearance really matter? The relationship between fluid appearance and cytology, cell counts, and chemical laboratory measurements in pleural effusions of patients with cancer

<p>Abstract</p> <p>Background</p> <p>Previous reports have suggested that the appearance of pleural effusions (i.e., the presence or absence of blood) might help to establish the etiology of the effusions. This study explores the relationship between pleural fluid appearance and the results of chemical and cytological analyses in a group of patients with recurrent symptomatic pleural effusions and a diagnosis of cancer.</p> <p>Methods</p> <p>Medical records were reviewed from all 390 patients who were diagnosed with cancer, who underwent thoracentesis before placement of an intrapleural catheter (IPC) between April 2000 and January 2006. Adequate information for data analysis was available in 365 patients. The appearance of their pleural fluid was obtained from procedure notes dictated by the pulmonologists who had performed the thoracenteses. The patients were separated into 2 groups based on fluid appearance: non-bloody and bloody. Group differences in cytology interpretation were compared by using the chi square test. Cellular counts, chemical laboratory results, and survival after index procedure were compared by using the student's t test.</p> <p>Results</p> <p>Pleural fluid cytology was positive on 82.5% of the non-bloody effusions and on 82.4% of the bloody ones. The number of red blood cells (220.5 × 10³/μL vs. 12.3 × 10³/μL) and LDH values (1914 IU/dl vs. 863 IU/dl) were statistically higher in bloody pleural effusions.</p> <p>Conclusion</p> <p>The presence or absence of blood in pleural effusions cannot predict their etiology in patients with cancer and recurrent symptomatic pleural effusions.</p

Clinical Audits in Outpatient Clinics for Chronic Obstructive Pulmonary Disease: Methodological Considerations and Workflow

Objectives: Previous clinical audits for chronic obstructive pulmonary disease (COPD) have provided valuable information on the clinical care delivered to patients admitted to medical wards because of COPD exacerbations. However, clinical audits of COPD in an outpatient setting are scarce and no methodological guidelines are currently available. Based on our previous experience, herein we describe a clinical audit for COPD patients in specialized outpatient clinics with the overall goal of establishing a potential methodological workflow.Methods: A pilot clinical audit of COPD patients referred to respiratory outpatient clinics in the region of Andalusia, Spain (over 8 million inhabitants), was performed. The audit took place between October 2013 and September 2014, and 10 centers (20% of all public hospitals) were invited to participate. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The usefulness of formally scheduled regular follow-up visits was assessed. Two different databases (resources and clinical database) were constructed. Assessments were planned over a year divided by 4 three-month periods, with the goal of determining seasonal-related changes. Exacerbations and survival served as the main endpoints.Conclusions: This paper describes a methodological framework for conducting a clinical audit of COPD patients in an outpatient setting. Results from such audits can guide health information systems development and implementation in real-world settings.This study was financially supported by an unrestricted grant from Laboratorios Menarini, SA (Barcelona, Spain)

A systematic review of the role of vitamin insufficiencies and supplementation in COPD

<p>Abstract</p> <p>Background</p> <p>Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD. The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms. Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy.</p> <p>Methods</p> <p>A systematic literature review was performed on the association of vitamins and COPD. The role of vitamin supplements in COPD was then evaluated.</p> <p>Conclusions</p> <p>The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function. High vitamin intake would probably reduce the annual decline of FEV1. There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function.</p

High-Anxious Individuals Show Increased Chronic Stress Burden, Decreased Protective Immunity, and Increased Cancer Progression in a Mouse Model of Squamous Cell Carcinoma

In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2–3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED), 3 times/week, 10-weeks). The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome), and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th), cytolytic (CTL), and regulatory (Treg) T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF) by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden), increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression), lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity), and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis). These results suggest that the deleterious effects of high trait anxiety could be: exacerbated by life-stressors, accentuated by the stress of cancer diagnosis/treatment, and mediate increased tumor progression and/or metastasis. Therefore, it may be beneficial to investigate the use of chemotherapy-compatible anxiolytic treatments immediately following cancer diagnosis, and during cancer treatment/survivorship