A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer

ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate specificity involved in the elimination of several carcinogens from the gut. Several polymorphic variants within the ABCB1 gene have been reported as modulators of ABCB1-mediated transport. We investigated the impact of ABCB1 genetic variants on colorectal cancer (CRC) risk. A hybrid tagging/functional approach was performed to select 28 single nucleotide polymorphisms (SNPs) that were genotyped in 1,321 Czech subjects, 699 CRC cases and 622 controls. In addition, six potentially functional SNPs were genotyped in 3,662 German subjects, 1,809 cases and 1,853 controls from the DACHS study. We found that three functional SNPs (rs1202168, rs1045642 and rs868755) were associated with CRC risk in the German population. Carriers of the rs1202168_T and rs868755_T alleles had an increased risk for CRC (Ptrend = 0.016 and 0.029, respectively), while individuals bearing the rs1045642_C allele showed a decreased risk of CRC (Ptrend = 0.022). We sought to replicate the most significant results in an independent case-control study of 3,803 subjects, 2,169 cases and 1,634 controls carried out in the North of Germany. None of the SNPs tested were significantly associated with CRC risk in the replication study. In conclusion, in this study of about 8,800 individuals we show that ABCB1 gene polymorphisms play at best a minor role in the susceptibility to CRC

Design Works! Sieben Thesen zum Verhältnis von Raum und Innovation

Räume haben einen wesentlichen Einfluss auf Innovation und Arbeitsleistung ihrer Nutzer. In sieben Thesen skizzieren die Autoren das Verhältnis von Raum und Innovation. Ihre Zusammenstellung liefert wertvolle Anhaltspunkte und Anregungen, wie dieser Spannungsbogen zum Wohle aller Beteiligten genutzt werden kann

Development and evaluation of a novel combined perfusion decellularization heart-lung model for tissue engineering of bioartificial heart-lung scaffolds

BACKGROUND: Bioengineered transplantable heart-lung scaffolds could be potentially lifesaving in a large number of congenital and acquired cardiothoracic disorders including terminal heart-lung disease. METHODS: We decellularized heart-lung organ-blocs from rats (n = 10) by coronary and tracheal perfusion with ionic detergents in a modified Langendorff circuit. RESULTS: In the present project, we were able to achieve complete decellularization of the heart-lung organ-bloc. Decellularized heart-lung organ-blocs lacked intracellular components but maintained structure of the cellular walls with collagen and elastic fibers. CONCLUSIONS: We present a novel model of combined perfusion and decellularization of heart-lung organ-blocs. This model is the first step on the pathway to creating bioengineered transplantable heart-lung scaffolds. We believe that further development of this technology could provide a life-saving conduit, significantly reducing the risks of heart-lung failure surgery and improving postoperative quality of life

Single-Center Real-World Experience with Sutureless Aortic Valve Prosthesis in Isolated and Combined Procedures

Introduction: Due to their favourable hemodynamic performance and the ability to enable minimally invasive access procedures, sutureless aortic valve prostheses have found their place in the armamentarium of cardiothoracic surgeons. In this study, we sought to review our institutional experience of sutureless aortic valve replacement (SU-AVR). Methods: We carried out a retrospective analysis of 200 consecutive patients who underwent an SU-AVR with a Perceval valve between December 2019 and February 2023. Results: The mean age of patients was 69.3 ± 8.1 years, and patients showed a moderate-risk profile with a mean logistic EuroSCORE-II of 5.2 ± 8.1%. An isolated SU-AVR was performed in 85 (42.5%) patients, concomitant CABG was performed in 75 (37.5%) and 40 patients (20%) underwent a multivalve procedure involving SU-AVR. The cardiopulmonary bypass (CPB) and cross-clamp (CC) times were 82.1 ± 35.1 and 55.5 ± 27.8 min, respectively. In-hospital, 30-day, 6-month and 1-year mortality rates were 4.5%, 6.5%, 7.5% and 8.2%, respectively. The postoperative transvalvular mean pressure gradient was 6.3 ± 1.6 mmHg and stayed stable over the follow-up time. We reported no cases of paravalvular leakage, and the incidence of stroke was 0.5%. Conclusions: With their favourable hemodynamic performance and shorter CC and CPB times, sutureless aortic valve prostheses facilitate minimally invasive access surgery, being a safe and durable promising approach for the surgical AVR

Sutureless aortic valve replacement in pure aortic regurgitation: expanding the indications

Background In the era of transcatheter methods, patients presenting with a pure aortic regurgitation (AR) are not considered eligible for transcatheter treatment and therefore require another less invasive surgical option. We sought to review our experience with sutureless aortic valve replacement (SU-AVR) in patients presenting with symptomatic pure AR, which until now is a contraindication for implementation of sutureless valve prostheses in Europe. Methods Between April 2018 and June 2021, 80 consecutive patients underwent a SU-AVR for various indications at our institution. We analyzed the outcomes and postoperative complications of 12 patients presenting with a pure severe AR undergoing SU-AVR using Perceval (Corcym). Results The mean age of the patients was 67 +/- 9.1 years old. All patients presented with symptomatic pure AR. Patients presented with multiple comorbidities as reflected by the mean EuroSCORE-II of 3.6 +/- 2.6%. Six patients (50%) underwent a concomitant CABG procedure. The mean operating- and cross clamp time was 127.25 +/- 45.9 and 40.33 +/- 17.3 min respectively. All isolated SU-AVR were performed via J-sternotomy or right anterolateral thoracotomy. There were no cases of device dislocation. No patients presented with a paravalvular leakage. We observed excellent mean postoperative pressure gradient at follow-up 5.7 +/- 1.5 mmHg. Conclusions Our experience with SU-AVR shows the feasibility of sutureless technologies in the aortic valve surgery due to pure AR. Besides the great technical success and excellent hemodynamics, SU-AVR in severe AR offers a great opportunity of reducing the invasivity of the surgical procedure and potentially reducing hospital cost without compromising the postoperative outcomes and in-hospital length of stay

Surgical treatment of infective endocarditis in intravenous drug abusers

BACKGROUND: Despite current progress in antibiotic therapy and medical management, infective endocarditis remains a serious condition presenting with high mortality rates. It also is a life-threatening complication in patients with a history of chronic intravenous drug abuse. In this study, we analyzed our institutional experience on the surgical therapy of infective endocarditis in patients with active intravenous drug abuse. The aim of the study is to identify the predictive factors of mortality and morbidity in this subgroup of patients.METHODS: Between 2007 and 2020, a total of 24 patients (7 female, mean age 38.5 ± 8.7) presenting with active intravenous drug abuse underwent a surgical treatment for the infective endocarditis at out center. The primary endpoint was survival at 30th day after the surgery. The secondary composite endpoint included freedom from death, recurrent endocarditis, re-do surgery, and postoperative stroke during the follow-up period. Mean follow-up was 4.2 ± 4.3 years.RESULTS: Staphylococcus species was the most common pathogen detected in the preoperative blood cultures. Infection caused by Enterococcus species as well as liver function impairment were identified as mortality predictor factors. Logistic EuroSCORE and EusoSCORE-II were also predictive factors for mortality in univariate analysis. Survival at 1 and 3 years was 78 and 72% respectively. Thirty-day survival was 88%. 30-day freedom from combined endpoint was 83% and after 1 and 3 years, 69 and 58% of the patients respectively were free from combined endpoint. Five patients (20.8%) were readmitted with recurrent infective endocarditis.CONCLUSION: In patients presenting with active intravenous drug abuse, treatment of infective endocarditis should be performed as aggressively as possible and should be followed by antibiotic therapy to avoid high mortality rates and recurrent endocarditis. Early intervention is advisable in patients with an infective endocarditis and enterococcus species in the preoperative blood cultures, liver function deterioration as well as cardiac function impairment. Attention should be also payed to addiction treatment, due to the elevated relapse rate in patients who actively inject drugs. However, larger prospective studies are necessary to support our results. As septic shock is the most frequent cause of death, new treatment options, e.g. blood purification should be evaluated.</p