The i148m Pnpla3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls

BACKGROUND: Reduced adiponectin is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), and the I148M Patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism predisposes to NAFLD and liver damage progression in NASH and chronic hepatitis C (CHC) by still undefined mechanisms, possibly involving regulation of adipose tissue function. Aim of this study was to evaluate whether the I148M PNPLA3 polymorphism influences serum adiponectin in liver diseases and healthy controls. METHODS: To this end, we considered 144 consecutive Italian patients with NAFLD, 261 with CHC, 35 severely obese subjects, and 257 healthy controls with very low probability of steatosis, all with complete clinical and genetic characterization, including adiponectin (ADIPOQ) genotype. PNPLA3 rs738409 (I148M) and ADIPOQ genotypes were evaluated by Taqman assays, serum adiponectin by ELISA. Adiponectin mRNA levels were evaluated by quantitative real-time PCR in the visceral adipose tissue (VAT) of 35 obese subjects undergoing bariatric surgery. RESULTS: Adiponectin levels were independently associated with the risk of NAFLD and with the histological severity of the disease. Adiponectin levels decreased with the number of 148\u2009M PNPLA3 alleles at risk of NASH both in patients with NAFLD (p\u2009=\u20090.03), and in healthy subjects (p\u2009=\u20090.04). At multivariate analysis, PNPLA3 148\u2009M alleles were associated with low adiponectin levels (<6\u2009mg/ml, median value) independently of NAFLD diagnosis, age, gender, BMI, and ADIPOQ genotype (OR 1.67, 95% c.i. 1.07-2.1 for each 148\u2009M allele). The p.148\u2009M PNPLA3 variant was associated with decreased adiponectin mRNA levels in the VAT of obese patients (p\u2009<\u20090.05) even in the absence of NASH. In contrast, in CHC, characterized by adiponectin resistance, low adiponectin was associated with male gender and steatosis, but not with PNPLA3 and ADIPOQ genotypes and viral features. CONCLUSIONS: The I148M PNPLA3 variant is associated with adiponectin levels in patients with NAFLD and in healthy subjects, but in the presence of adiponectin resistance not in CHC patients. The I148M PNPLA3 genotype may represent a genetic determinant of serum adiponectin levels. Modulation of serum adiponectin might be involved in mediating the susceptibility to steatosis, NASH, and hepatocellular carcinoma in carriers of the 148\u2009M PNPLA3 variant without CHC, with potential therapeutic implications

Left sleeve pneumonectomy via a clamshell incision for lung cancer with carinal invasion: Report of a case

Surgery for lung cancer involving the carina is challenging as it requires special surgical techniques and airway management. We report how we successfully treated carinal invasion of primary lung cancer by performing left sleeve pneumonectomy through a clamshell incision, as bilateral thoracotomy through a transverse sternotomy. Without a cardiopulmonary assist device, adequate ventilation and oxygenation were maintained across the operative field with a spinal tube. Tracheobronchial anastomosis was relatively easy to perform, with an excellent surgical view. The patient had an uneventful postoperative course and was discharged from hospital without oxygen support. There was no evidence of complications at the anastomosis on chest computed tomography and no sign of recurrence during 6 months of follow-up. The clamshell incision approach provided an excellent surgical view without the need to change the position of the patient during the operation. Thus, it could prove a useful procedure for carinal surgery; especially left sleeve pneumonectomy.The original publication is available at www.springerlink.co

Do genetic factors protect for early onset lung cancer? A case control study before the age of 50 years

<p>Abstract</p> <p>Background</p> <p>Early onset lung cancer shows some familial aggregation, pointing to a genetic predisposition. This study was set up to investigate the role of candidate genes in the susceptibility to lung cancer patients younger than 51 years at diagnosis.</p> <p>Methods</p> <p>246 patients with a primary, histologically or cytologically confirmed neoplasm, recruited from 2000 to 2003 in major lung clinics across Germany, were matched to 223 unrelated healthy controls. 11 single nucleotide polymorphisms of genes with reported associations to lung cancer have been genotyped.</p> <p>Results</p> <p>Genetic associations or gene-smoking interactions was found for <it>GPX1(Pro200Leu) </it>and <it>EPHX1(His113Tyr)</it>. Carriers of the Leu-allele of <it>GPX1(Pro200Leu) </it>showed a significant risk reduction of OR = 0.6 (95% CI: 0.4–0.8, p = 0.002) in general and of OR = 0.3 (95% CI:0.1–0.8, p = 0.012) within heavy smokers. We could also find a risk decreasing genetic effect for His-carriers of <it>EPHX1(His113Tyr) </it>for moderate smokers (OR = 0.2, 95% CI:0.1–0.7, p = 0.012). Considered both variants together, a monotone decrease of the OR was found for smokers (OR of 0.20; 95% CI: 0.07–0.60) for each protective allele.</p> <p>Conclusion</p> <p>Smoking is the most important risk factor for young lung cancer patients. However, this study provides some support for the T-Allel of <it>GPX1(Pro200Leu) </it>and the C-Allele of <it>EPHX1(His113Tyr) </it>to play a protective role in early onset lung cancer susceptibility.</p

Torace : Malattie della pleura

Le malattie della pleura comprendono il pneumotorace, l\u2019emotorace, il chilotorace, l\u2019empiema pleurico, i tumori primitivi e secondari della pleura. Queste patologie risultano di grande interesse in quanto presentano un\u2019elevata frequenza e necessitano di una precisa diagnosi differenziale con altre malattie. Il pneumotorace spontaneo primitivo, con un\u2019incidenza di 18-28 casi/anno ogni 100.000 abitanti per il sesso maschile, rappresenta una patologia che certamente il laureato in medicina e chirurgia verr\ue0 chiamato a trattare nel corso della professione medica; il suo inquadramento diagnostico e terapeutico risulta fondamentale. L\u2019empiema pleurico costituisce una possibile e frequente complicanza in seguito ad un processo infiammatorio acuto del polmone. Tale patologia deve essere precocemente diagnosticata al fine di non incorrere in gravi complicanze che possono determinare importanti reliquati sulla meccanica respiratoria. Le neoplasie maligne della pleura sono in continuo aumento e in considerazione della aspecifica sintomatologia costituiscono una patologia di grande interesse diagnostico e terapeutico