Mutations of the TP53 gene occur in a subset of patients with acute myeloid leukemia (AML) and confer an exceedingly adverse prognosis. However, whether different types of TP53 mutations exert a uniformly poor outcome has not been investigated yet. Here, we addressed this issue by analyzing data of 1537 patients intensively treated within protocols of the German-Austrian AML study group. We classified TP53 mutations depending on their impact on protein structure and according to the evolutionary action (EAp53) score and the relative fitness score (RFS). In 98/1537 (6.4%) patients, 108 TP53 mutations were detected. While the discrimination depending on the protein structure and the EAp53 score did not show a survival difference, patients with low-risk and high-risk AML-specific RFS showed a different overall survival (OS; median, 12.9 versus 5.5 months, p = 0.017) and event-free survival (EFS; median, 7.3 versus 5.2 months, p = 0.054). In multivariable analyses adjusting for age, gender, white blood cell count, cytogenetic risk, type of AML, and TP53 variant allele frequency, these differences were statistically significant for both OS (HR, 2.14; 95% CI, 1.15–4.0; p = 0.017) and EFS (HR, 1.97; 95% CI, 1.06–3.69; p = 0.033). We conclude that the AML-specific RFS is of prognostic value in patients with TP53-mutated AML and a useful tool for therapeutic decision-making.

Oral anticoagulation therapy (OAT) is a challenge in general practice, especially for high-risk groups such as the elderly. Insufficient patient knowledge about safety-relevant aspects of OAT is considered to be one of the main reasons for complications. The research question addressed in this manuscript is whether a complex intervention that includes practice-based case management, self-management of OAT and additional patient and practice team education improves patient knowledge about anticoagulation therapy compared to a control group of patients receiving usual care (as a secondary objective of the Primary Care Management for Optimised Antithrombotic Treatment (PICANT) trial). The cluster-randomised controlled PICANT trial was conducted in 52 general practices in Germany, between 2012 and 2015. Trial participants were patients with a long-term indication for oral anticoagulation. A questionnaire was used to assess knowledge at baseline, after 12, and after 24 months. The questionnaire consists of 13 items (with a range of 0 to 13 sum-score points) covering topics related to intervention. Differences in the development of patient knowledge between intervention and control groups compared to baseline were assessed for each follow-up by means of linear mixed-effects models. Seven hundred thirty-six patients were included at baseline, of whom 95.4% continued to participate after 12 months, and 89.3% after 24 months. The average age of patients was 73.5 years (SD 9.4), and they mainly suffered from atrial fibrillation (81.1%). Patients in the intervention and control groups had similar knowledge about oral anticoagulation at baseline (5.6 (SD 2.3) in both groups). After 12 months, the improvement in the level of knowledge (compared to baseline) was significantly larger in the intervention group than in the control group (0.78 (SD 2.5) vs. 0.04 (SD 2.3); p = 0.0009). After 24 months, the difference between both groups was still statistically significant (0.6 (SD 2.6) vs. -0.3 (SD 2.3); p = 0.0001). Since this intervention was effective, it should be established in general practice as a means of improving patient knowledge about oral anticoagulation. Current controlled trials ISRCTN41847489 ; Date of registration: 13/04/2012

Introduction: Magnesium (Mg²⁺) deficiency is a common finding in the early phase after kidney transplantation (KT) and has been linked to immune dysfunction and infections. Data on the association of hypomagnesemia and the rate of infections in kidney transplant recipients (KTRs) are sparse. Methods: We conducted a single-center retrospective cohort study of KTRs transplanted between 2005 and 2015. Laboratory data, including serum Mg²⁺ (median time of the Mg²⁺ measurement from KT: 29 days), rate of infections including mainly urinary tract infections (UTI), and common transplant-related viral infections (CMV, polyoma, EBV) in the early phase after KT were recorded. The primary outcome was the incidence of infections within one year after KT, while secondary outcomes were hospitalization due to infection, incidence rates of long-term (up to two years) infections, and all-cause mortality. Results: We enrolled 376 KTRs of whom 229 patients (60.9%) suffered from Mg²⁺ deficiency defined as a serum Mg²⁺ < 0.7 mmol/L. A significantly higher incidence rate of UTIs and viral infections was observed in patients with versus without Mg²⁺ deficiency during the first year after KT (58.5% vs. 47.6%, p = 0.039 and 69.9% vs. 51.7%, p < 0.001). After adjustment for potential confounders, serum Mg²⁺ deficiency remained an independent predictor of both UTIs and viral infections (odds ratio (OR): 1.73, 95% CI: 1.04–2.86, p = 0.035 and OR: 2.05, 95% CI: 1.23–3.41, p = 0.006). No group differences according to Mg²⁺ status in hospitalizations due to infections and infection incidence rates in the 12–24 months post-transplant were observed. In the Cox regression analysis, Mg²⁺ deficiency was not significantly associated with all-cause mortality (HR: 1.15, 95% CI: 0.70–1.89, p = 0.577). Conclusions: KTRs suffering from Mg²⁺ deficiency are at increased risk of UTIs and viral infections in the first year after KT. Interventional studies investigating the effect of Mg²⁺ supplementation on Mg²⁺ deficiency and viral infections in KTRs are needed.

Background: Women with polycystic ovary syndrome (PCOS) are more prone to autoimmune thyroiditis, and both disorders lead to subfertility and pregnancy-related complications. The aim of this study was to investigate whether mothers with and without PCOS and their offspring have comparable thyroid parameters at term and how thyroid parameters are associated with perinatal outcome in this population. Methods: This cross-sectional observational study was performed in a single academic tertiary hospital in Austria. Seventy-nine pregnant women with PCOS and 354 pregnant women without PCOS were included. Blood samples were taken from the mother and cord blood at birth. Primary outcome parameters were maternal and neonatal thyroid parameters at delivery. Secondary outcome parameters were the composite complication rate per woman and per neonate. Results: Thyroid dysfunction was more prevalent among PCOS women (p < 0.001). At time of birth, free triiodothyronine (fT3) levels were significantly lower in PCOS than in non-PCOS women (p = 0.005). PCOS women and their neonates had significantly higher thyreoperoxidase antibody (TPO-AB) levels (p = 0.001). Women with elevated TPO-AB had a significantly higher prevalence of hypothyroidism (p < 0.001). There was a significant positive correlation between maternal and neonatal free thyroxine, fT3 and TPO-AB levels. There were no significant differences in thyroid parameters between women or neonates with or without complications. Conclusions: Our results demonstrate a higher prevalence of thyroid dysfunction and autoimmunity in PCOS women, supporting a common etiology of both disorders. We were not able to show an association between complication rate and thyroid parameters.

The gut-liver axis is of upmost importance for the development of infections after surgery. Further bacterial translocation due to surgery-related dysbiosis is associated with limited detoxification function of the liver compromising outcome of surgical therapy. After liver surgery, about 30% of patients develop a bacterial infection, with the risk of bacteremia or even sepsis-associated liver failure and mortality in >40%. The potential benefit of pro-/synbiotics given before surgery is still under debate. Thus, a systematic literature search on trials comparing patients with or without supplementation and outcome after liver resection or transplantation was performed. Our search strategy revealed 12 relevant studies on perioperative administration of pro-/synbiotics in liver surgery. The pro-/synbiotic combinations and concentrations as well as administration timeframes differed between studies. Five studies were performed in liver transplantation and 7 in liver resection. All studies but one reported lower infection rates (pooled RR: 0.46, 95% CI: 0.31–0.67) with pro-/synbiotics. Liver function was assessed after LT/LR in 3 and 5 studies, respectively. Pro-/synbiotics improved function in 1/3 and 2/5 studies, respectively. Concluding, perioperative pro-/synbiotics clearly reduce infection after liver surgery. However, standard protocols with both well-defined probiotic strain preparations and administration timeframes are pending.

To provide insights into visiting policies and family-centred care practices with a focus on children as visitors in Intensive Care Units in German-speaking countries. Online-survey with a mixed methods approach. Leading clinicians (n = 1943) from German-speaking countries were invited to participate. Outcomes included the percentage of intensive care units with open visiting policies, age restrictions, family-centred care activities and barriers. Paediatric, mixed and adult units In total, 19.8% (n = 385) of the clinicians responded. Open visiting times were reported by 36.3% (n = 117), with significant differences between paediatric (79.2%), adult (21.3%) and mixed-age (41.2%) units (p < 0.01). Two-thirds of clinicians stated that their units had no age restrictions for children as visitors (n = 221, 68.4%). The family-centred care activities most frequently implemented were open visiting times and dissemination of information. Significantly more German units have open visiting policies and more Swiss units allow children as visitors, compared to the other countries (both p < 0.001). Barriers to family-centred care were concerns about children being traumatized, infection and workload. The majority reported that family-centred care policies had been implemented in their units, including open visiting policies, allowing children as visitors without age restriction and other family-centred care activities.