Gene polymorphisms in APOE, NOS3, and LIPC genes may be risk factors for cardiac adverse events after primary CABG

<p>Abstract</p> <p>Introduction</p> <p>Coronary artery disease progression after primary coronary artery bypass grafting may, beside classical atherosclerosis risk factors, be depending on genetic predisposition.</p> <p>Methods</p> <p>We investigated 192 CABG patients (18% female, age: 60.9 ± 7.4 years). Clinically cardiac adverse events were defined as need for reoperation (n = 88; 46%), reintervention (n = 58; 30%), or angina (n = 89; 46%). Mean follow-up time measured 10.1 ± 5.1 years. Gene polymorphisms (<b><it>ApoE, NOS3, LIPC, CETP, SERPINE-1, Prothrombin</it></b>) were investigated separately and combined (gene risk profile).</p> <p>Results</p> <p>Among classical risk factors, arterial hypertension and hypercholesterinemia significantly influenced CAD progression. Single <b><it>ApoE, NOS3 </it></b>and <b><it>LIPC </it></b>polymorphisms provided limited information. Patients missing the most common <b><it>ApoE </it></b>ε3 allele (5,2%), showed recurrent symptoms (p = 0,077) and had more frequently reintervention (p = 0,001). <b><it>NOS3 </it></b>a allele was associated with a significant increase for reintervention (p = 0,041) and recurrent symptoms (p = 0,042).</p> <p>Homozygous <b><it>LIPC </it></b>patients had a higher reoperation rate (p = 0.049).</p> <p>A gene risk profile enabled us to discriminate between faster and slower occurrence of cardiac adverse events (p = 0.0012).</p> <p>Conclusion</p> <p>Single <b><it>APOE, LIPC </it></b>and <b><it>NOS3 </it></b>polymorphisms permitted limited prognosis of cardiac adverse events in patients after CABG. Risk profile, in contrast, allowed for risk stratification.</p

Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

Background and aimsAutoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens.MethodsWe retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary endpoint was complete remission, defined as the absence of clinical symptoms and resolution of the index radiological pancreatic abnormalities attributed to AIP.ResultsWe included 735 individuals with AIP (69% male; median age 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, while 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower ( 2 weeks (OR 0.908; 95%CI 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (OR 0.639; 95%CI 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid tapering duration, induction treatment duration, and total cumulative dose.ConclusionPatients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens

The Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICA)

To explore the various couplings across space and time and between ecosystems in a consistent manner, atmospheric modeling is moving away from the fractured limited-scale modeling strategy of the past toward a unification of the range of scales inherent in the Earth system. This paper describes the forward-looking Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICA), which is intended to become the next-generation community infrastructure for research involving atmospheric chemistry and aerosols. MUSICA will be developed collaboratively by the National Center for Atmospheric Research (NCAR) and university and government researchers, with the goal of serving the international research and applications communities. The capability of unifying various spatiotemporal scales, coupling to other Earth system components, and process-level modularization will allow advances in both fundamental and applied research in atmospheric composition, air quality, and climate and is also envisioned to become a platform that addresses the needs of policy makers and stakeholders

Analysis of internal construct validity of the SRS-24 questionnaire

PURPOSE: The SRS-24 questionnaire was originally validated using methods of classical test theory, but internal construct validity has never been shown. Internal construct validity, i.e. unidimensionality and linearity, is a fundamental arithmetic requirement and needs to be shown for a scale for summating any set of Likert-type items. Here, internal construct validity of the SRS-24 questionnaire in adolescent idiopathic scoliosis (AIS) patients is analyzed. METHODS: 232 SRS-24 questionnaires distributed to 116 patients with AIS pre-operatively and at postoperative follow-up were analyzed. 103 patients were females; the average age was 16.5 ± 7.1 years. The questionnaires were subjected to Rasch analysis using the RUMM2020 software package. RESULTS: All seven domains of the SRS-24 showed misfit to the Rasch model, and three of seven were unidimensional. Unidimensionality and linearity could only be achieved for an aggregate score by separating pre- and postoperative items and omitting items which caused model misfit. Reducing the questionnaire to six pre-operative items (p = 0.098; 2.25% t tests) and five postoperative items (p = 0.267; 3.70% t tests) yields model fit and unidimensionality for both summated scores. The person-separation indices (PSI) were 0.67 and 0.69, respectively, for the pre- and postoperative patients. CONCLUSIONS: The SRS-24 score is a non-linear and multidimensional construct. Adding the items into a single value is therefore not supported and invalid in principle. Making profound changes to the questionnaire yields a score which fulfills the properties of internal construct validity and supports its use a change score for outcome measurement