Prophylactic CMV therapy does not improve three‐yr patient and graft survival compared to preemptive therapy

Despite increasing evidence in favor of prophylactic valganciclovir treatment in kidney transplant recipients for the prevention of cytomegalovirus (CMV) infection, the impact of preemptive vs. prophylactic treatment on long‐term clinical outcomes is unclear. In this retrospective study, 187 kidney transplant recipients with serologic intermediate‐risk constellation (recipient CMV IgG positive) received either preemptive or prophylactic treatment with valganciclovir. Patient survival (primary endpoint), graft survival, viremia rates, and other CMV‐related outcomes were analyzed. Prophylactic therapy reduced the rates for CMV viremia during the first year (hazard ratio: 0.48, 95% confidence interval [CI] 0.30–0.75; p < 0.001). There was a trend for higher three‐yr patient mortality in the prophylactic group (hazard ratio: 5.08, 95% CI 0.62–41.3; p = 0.091), and the rate of graft loss was not reduced (hazard ratio: 0.93, 95% CI 0.32–2.68; p = 0.894). Estimated glomerular filtration rate over three yr was on average 6.8 mL/min/1.73 m² lower in the prophylactic group (95% CI −11.68 to −1.81; p = 0.007) using a multivariate random effects model but showed more improvement over time. Prophylactic valganciclovir treatment reduced the rate of CMV infections during the first year post‐transplant but no effects of prophylactic treatment on patient and graft survival or kidney function over three yr were observed.     

Thermal unfolding and refolding of a lytic polysaccharide monooxygenase from Thermoascus aurantiacus

Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes which promote the degradation of recalcitrant polysaccharides like cellulose or chitin. Here, we have investigated the thermostability of an LPMO from Thermoascus aurantiacus (TaLPMO9A). TaLPMO9A was found to retain most of its initial activity after incubating at 100 °C while its apparent melting temperature (T_m) is 69 °C at neutral pH. Interestingly, our studies show that holoTaLPMO9A, apoTaLPMO9A and deglycosylated TaLPMO9A can fold back to their original conformation upon lowering the temperature. In the presence of β-mercaptoethanol the protein does not refold. Activity of TaLPMO9A and refolded TaLPMO9A was studied by an Amplex® Red assay as well as by TaLPMO9A catalysed oxidation of phosphoric acid swollen cellulose (PASC). These studies confirm the functional regain of TaLPMO9A activity upon going through one cycle of unfolding and refolding. The thermal unfolding and refolding of TaLPMO9A was measured spectroscopically. Utilizing the two-state model, detailed thermodynamic parameters were obtained for holoTaLPMO. Furthermore, we have investigated the kinetics of TaLPMO9A unfolding and refolding. Our results have implications in understanding LPMO stability, which is crucial for the efficient application of LPMOs as biocatalysts during biomass degradation.

TaLPMO9A regains its catalytic power after a thermal unfolding and refolding cycle.     

Advances in radiotherapy and targeted therapies for rectal cancer

The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related toxicity.In addition,the administration of a simultaneous integrated boost offers excellent local control rates.The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches.However,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread.The expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient outcomes.On the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape.Both N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings.Therefore,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.     

Looking for a Learning Curve in EVAR Based on the Zenith Stent Graft

The purpose of this study was to report the learning curve of endovascular aneurysm repair (EVAR) based on the Zenith stent graft (Cook Medical Inc., Bloomington, IN). In the last 9 years, 101 patients were treated with a Zenith stent graft. To display the learning curve, a cumulative sum (CUSUM) failure analysis curve of the 30-day technical success rate was calculated. For detailed analysis, our EVAR patient cohort was chronologically divided into three groups. Technical and clinical results, basic patient parameters, and procedural data were compared. The CUSUM graph indicated an initial sharp rise within the first 35 cases and a plateau thereafter. The 30-day technical success rate significantly increased from the first to the second group (83 vs. 100%; p = 0.019), as did the primary technical success rate (66 vs. 97%; p = 0.001). EVAR based on the Zenith stent graft required ∼35 cases to reach a stably high rate of short-term technical success.