Chronic Obstructive Pulmonary Disease: Diagnosis and Management.

Chronic obstructive pulmonary disease (COPD) affects nearly 6% of Americans. Routine screening for COPD in asymptomatic adults is not recommended. Patients with suspected COPD should have the diagnosis confirmed with spirometry. Disease severity is based on spirometry results and symptoms. The goals of treatment are to improve quality of life, reduce exacerbations, and decrease mortality. Pulmonary rehabilitation improves lung function and increases patients' sense of control, and it is effective for improving symptoms and reducing exacerbations and hospitalizations in patients with severe disease. Initial pharmaceutical treatment is based on disease severity. For mild symptoms, initial treatment with a long-acting muscarinic antagonist is recommended. If symptoms are uncontrolled with monotherapy, dual therapy with a long-acting muscarinic antagonist/long-acting beta2 agonist combination should be initiated. Triple therapy with a long-acting muscarinic antagonist/long-acting beta2 agonist/inhaled corticosteroid combination improves symptoms and lung function more than dual therapy but increases pneumonia risk. Phosphodiesterase-4 inhibitors and prophylactic antibiotics can improve outcomes in some patients. Mucolytics, antitussives, and methylxanthines do not improve symptoms or outcomes. Long-term oxygen therapy improves mortality in patients with severe resting hypoxemia or with moderate resting hypoxemia and signs of tissue hypoxia. Lung volume reduction surgery reduces symptoms and improves survival in patients with severe COPD, whereas a lung transplant improves quality of life but does not improve long-term survival.

Versatility of Pedicled Perforator-Based V-Y Advancement Flaps for Reconstruction of the Upper Limb: A Case Series and Review of the Literature.

INTRODUCTION: The aim of any reconstruction is to provide a robust and cosmetically pleasing result that does not significantly alter function. We describe our experience of using the V-Y principle in advancement flaps designed around a distinct perforator to reconstruct soft tissue defects of the upper limb. The shortcomings of fasciocutaneous and fascial flaps requiring skin grafting can be eliminated. METHODS: This was a 10-year retrospective review of patients who had V-Y flaps based on a distinct perforator for defects of the shoulder, axilla, arm, elbow, forearm, wrist, and hand. Defects of the digits and thumb were excluded. RESULTS: There were 59 flaps in 52 patients with an average age of 44 years (18-72 years). Skin malignancy was the most common primary etiology. The average defect size was 35 cm (9-80 cm). There were no total flap failures; however, there were 4 partial losses, which healed by secondary intention. Seven flaps had to be explored for the hematoma evacuation. CONCLUSIONS: The use of V-Y flaps based on distinct perforators in the upper limb retains limb aesthetics, allows early mobility and is a safe and reliable technique.

Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.

Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled-Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC-3 cells with 5-Aza-CdR reactivated 39 genes (≥ 2-fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.