Impact of the indexed effective orifice area on mid-term cardiac-related mortality after aortic valve replacement

Background There has been ongoing controversy as to whether prosthesis-patient mismatch (PPM, defined as indexed effective orifice area (EOAI) <0.85 m(2)/cm(2)) influences mortality after aortic valve replacement (AVR). In most studies, PPM is anticipated by reference tables based on mean EOAs as opposed to individual assessment. These reference values may not reflect the actual in vivo EOAI and hence, the presence or absence of PPM may be based on false assumptions. Objective To assess the impact of small prosthesis EOA on survival after aortic valve replacement AVR. Methods 645 patients had undergone an AVR between 2000 and 2007 entered the study. All patients underwent transthoracic echocardiography for determination of the actual EOAI within 6 months postoperatively. In order to predict time from surgery to death a proportional hazards model for competing risks (cardiac death vs death from other causes) was used. EOAI was entered as a continuous variable. Results PPM occurred in 40% of the patients. After a median follow-up of 2.35 years, 92.1% of the patients were alive. The final Cox regression model showed a significantly increased risk for cardiac death among patients with a smaller EOAI (HR=0.32, p=0.022). The effect of EOAI on the 2-5 year mortality risk was demonstrated by risk plots. Conclusions In contrast to previous studies these EOAI values were obtained through postoperative echocardiography, substantially improving the accuracy of measurement, and the EOAI was modelled as a continuous variable. There was a significantly improved survival for larger EOAIs following AVR. Strategies to avoid PPM should become paramount during AVR

Seasonal variation of Pneumocystis jirovecii infection: analysis of underlying climatic factors

AbstractPneumocystis jirovecii causes severe pneumonia (PCP) in immunocompromised patients. Seasonal changes of PCP incidence may be associated with climate changes. In this first study using multiple linear regression statistics to assess monthly climatic data and Pneumocystis, PCP incidence was positively correlated with mean temperature, but not with rainfall or wind strength

Radioembolization with Yttrium-90 microspheres (SIRT) in pancreatic cancer patients with liver metastases: Efficacy, safety and prognostic factors

OBJECTIVE To analyze the clinical efficacy of (90)Y radioembolization in liver metastases from pancreatic cancer, to describe treatment toxicities and to identify biomarkers as predictors of outcome. METHODS Data from 19 pancreatic cancer patients (9 females/10 males) who had received (90)Y radioembolization for metastatic liver disease between 06/2004 and 01/2011 were analyzed retrospectively. RESULTS The median age at (90)Y radioembolization was 63 years (range 43-77). In 16 patients, previous palliative gemcitabine-based chemotherapy was given for metastatic disease. Objective response in the liver after (90)Y radioembolization was 47%. Median local progression-free survival in the liver was 3.4 months (range 0.9-45.0). Median overall survival (OS) was 9.0 months (range 0.9-53.0) and 1-year survival was 24%. Cox regression models for baseline biomarkers at (90)Y radioembolization revealed correlations of increased carbohydrate antigen 19-9 (p = 0.02) and C-reactive protein (p = 0.03) with shorter OS. Short-term adverse events (nausea, vomiting, fatigue, fever and abdominal pain) did not exceed grade 3. As long-term adverse events, liver abscesses, gastroduodenal ulceration, cholestasis and cholangitis, ascites and spleen infarction were observed. CONCLUSION (90)Y radioembolization is able to induce an encouraging local response rate of liver metastases of pancreatic cancer patients. Most short-term toxicities are manageable; however, patients should be followed up carefully for severe long-term toxicities

Spirometry reference equations for central European populations from school age to old age.

Spirometry reference values are important for the interpretation of spirometry results. Reference values should be updated regularly, derived from a population as similar to the population for which they are to be used and span across all ages. Such spirometry reference equations are currently lacking for central European populations. To develop spirometry reference equations for central European populations between 8 and 90 years of age. We used data collected between January 1993 and December 2010 from a central European population. The data was modelled using "Generalized Additive Models for Location, Scale and Shape" (GAMLSS). The spirometry reference equations were derived from 118'891 individuals consisting of 60'624 (51%) females and 58'267 (49%) males. Altogether, there were 18'211 (15.3%) children under the age of 18 years. We developed spirometry reference equations for a central European population between 8 and 90 years of age that can be implemented in a wide range of clinical settings

Impact of the Specific Mutation in KRAS Codon 12 Mutated Tumors on Treatment Efficacy in Patients with Metastatic Colorectal Cancer Receiving Cetuximab-Based First-Line Therapy: A Pooled Analysis of Three Trials

Purpose: This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic colorectal cancer (mCRC). Patients: Overall, 119 patients bearing a KRAS mutation in codon 12 were evaluated. All patients received cetuximab-based first-line chemotherapy within the Central European Cooperative Oncology Group (CECOG), AIO KRK-0104 or AIO KRK-0306 trials. Results: Patients with KRAS codon 12 mutant mCRC showed a broad range of outcome when treated with cetuximab-based first-line regimens. Patients with tumors bearing a KRAS p.G12D mutation showed a strong trend to a more favorable outcome compared to other mutations (overall survival 23.3 vs. 14-18 months; hazard ratio 0.66, range 0.43-1.03). An interaction model illustrated that KRAS p.G12C was associated with unfavorable outcome when treated with oxaliplatin plus cetuximab. Conclusion: The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy. Copyright (C) 2012 S. Karger AG, Base

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Base

Multicenter evaluation of blood-based biomarkers for the detection of endometriosis and adenomyosis: A prospective non-interventional study.

OBJECTIVE To evaluate blood-based biomarkers to detect endometriosis and/or adenomyosis across nine European centers (June 2014-April 2018). METHODS This prospective, non-interventional study assessed the diagnostic accuracy of 54 blood-based biomarker immunoassays in samples from 919 women (aged 18-45 years) with suspicion of endometriosis and/or adenomyosis versus symptomatic controls. Endometriosis was stratified by revised American Society for Reproductive Medicine stage. Symptomatic controls were "pathologic symptomatic controls" or "pathology-free symptomatic controls". The main outcome measure was receiver operating characteristic-area under the curve (ROC-AUC) and Wilcoxon P values corrected for multiple testing (q values). RESULTS CA-125 performed best in "all endometriosis cases" versus "all symptomatic controls" (AUC 0.645, 95% confidence interval [CI] 0.600-0.690, q < 0.001) and increased (P < 0.001) with disease stage. In "all endometriosis cases" versus "pathology-free symptomatic controls", S100-A12 performed best (AUC 0.692, 95% CI 0.614-0.769, q = 0.001) followed by CA-125 (AUC 0.649, 95% CI 0.569-0.729, q = 0.021). In "adenomyosis only cases" versus "symptomatic controls" or "pathology-free symptomatic controls", respectively, the top-performing biomarkers were sFRP-4 (AUC 0.615, 95% CI 0.551-0.678, q = 0.045) and S100-A12 (AUC 0.701, 95% CI 0.611-0.792, q = 0.004). CONCLUSION This study concluded that no biomarkers tested could diagnose or rule out endometriosis/adenomyosis with high certainty