Current Knowledge and Implications From a European Perspective

The COVID-19 pandemic is one of the most serious health and economic crises of the 21st century. From a psychological point of view, the COVID-19 pandemic and its consequences can be conceptualized as a multidimensional and potentially toxic stressor for mental health in the general population. This selective literature review provides an overview of longitudinal studies published until June 2021 that have investigated the impact of the COVID-19 pandemic on mental health in the European population. Risk and protective factors identified in the studies are summarized. Forty-two studies that met inclusion and search criteria (COVID-19, mental health, longitudinal, and Europe) in PubMed, PsycInfo, and Web of Science databases indicate differential effects of the pandemic on mental distress, depression, and anxiety, depending on samples and methods used. Age-specific (e.g., young age), social (e.g., female, ethnical minority, loneliness), as well as physical and mental health-related factors (e.g., pre-pandemic illness) were identified as risk factors for poor mental health. The studies point to several protective factors such as social support, higher cognitive ability, resilience, and self-efficacy. Increasing evidence supports the assumption of the pandemic being a multidimensional stressor on mental health, with some populations appearing more vulnerable than others, although inconsistencies arise. Whether the pandemic will lead to an increase in the prevalence of mental disorders is an open question. Further high-quality longitudinal and multi-national studies and meta-analyses are needed to draw the complete picture of the consequences of the pandemic on mental health

Mental Health in Times of the COVID-19 Pandemic

The COVID-19 pandemic is one of the most serious health and economic crises of the 21st century. From a psychological point of view, the COVID-19 pandemic and its consequences can be conceptualized as a multidimensional and potentially toxic stressor for mental health in the general population. This selective literature review provides an overview of longitudinal studies published until June 2021 that have investigated the impact of the COVID-19 pandemic on mental health in the European population. Risk and protective factors identified in the studies are summarized. Forty-two studies that met inclusion and search criteria ( COVID-19, mental health, longitudinal, and Europe) in PubMed, PsycInfo, and Web of Science databases indicate differential effects of the pandemic on mental distress, depression, and anxiety, depending on samples and methods used. Age-specific (e.g., young age), social (e.g., female, ethnical minority, loneliness), as well as physical and mental health-related factors (e.g., pre-pandemic illness) were identified as risk factors for poor mental health. The studies point to several protective factors such as social support, higher cognitive ability, resilience, and self-efficacy. Increasing evidence supports the assumption of the pandemic being a multidimensional stressor on mental health, with some populations appearing more vulnerable than others, although inconsistencies arise. Whether the pandemic will lead to an increase in the prevalence of mental disorders is an open question. Further high-quality longitudinal and multi-national studies and meta-analyses are needed to draw the complete picture of the consequences of the pandemic on mental health.Peer Reviewe

Influence of lipid profile and statin administration on arterial stiffness in renal transplant recipients

Background: Hyperlipidemia is one of the major risk factors for developing a cardiovascular disease (CVD) and it is a frequent post-transplant complication, occurring in up to 60% of the renal transplant recipients (RTRs). Lipid lowering therapy with HMG-CoA reductase inhibitors (statins) is generally recommended and may reduce the overall cardiovascular risk. The aim of this study was to evaluate the lipid profile, statin administration and their relationship with arterial stiffness parameters in renal transplant recipients. Methods: Three hundred and forty-four stable RTRs (62.5% male) transplanted between 1994 and 2018 were randomly enrolled to the study. The following parameters of arterial stiffness was measured in each patient: carotid femoral pulse wave velocity (baPWV left and right, cfPWV) and pulse pressure (PP right and left). The study group was divided based on the use statins: 143 (41.6%) and 201 (58.4%). RTRs were qualified to the statin (+) and the statin (–) group, respectively. Results: In the statin (+) as compared to statin (–) group there were more patients with a CVD (32.9% vs. 14.9%) and diabetes (25.2% vs. 14.4%). In the whole study group, CVD was associated with a significant increase of both baPWV and cfPWV as well as PP (8.5 mmHg). There were significant differences in arterial stiffness parameters (baPWV, cfPWV, PP) between the statin (+) and the statin (–) group. Conclusions: Arterial stiffness was increased in RTRs with CVD and hyperlipidemia. The control of hyperlipidemia was poor in RTRs

Four-year update of the EXIST-2 study

Objectives We examined the long-term effects of everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. Methods Following favorable results from the double- blind core phase of EXIST-2 (NCT00790400), patients were allowed to receive open-label everolimus (extension phase). Patients initially randomly assigned to everolimus continued on the same dose; those who were receiving placebo crossed over to everolimus 10 mg/day. Dose modifications were based on tolerability. The primary end point was angiomyolipoma response rate, defined as a ≥50% reduction from baseline in the sum volume of target renal angiomyolipomas in the absence of new target angiomyolipomas, kidney volume increase of >20% from nadir, and angiomyolipoma-related bleeding grade ≥2. The key secondary end point was safety. Results Of the 112 patients who received ≥1 dose of everolimus, 58% (95% CI, 48.3% to 67.3%) achieved angiomyolipoma response. Almost all patients (97%) experienced reduction in renal lesion volumes at some point during the study period. Median duration of everolimus exposure was 46.9 months. Sixteen (14.3%) patients experienced angiomyolipoma progression at some point in the study. No angiomyolipoma-related bleeding or nephrectomies were reported. One patient on everolimus underwent embolization for worsening right flank pain. Subependymal giant cell astrocytoma lesion response was achieved in 48% of patients and skin lesion response in 68% of patients. The most common adverse events suspected to be treatment-related were stomatitis (42%), hypercholesterolemia (30.4%), acne (25.9%), aphthous stomatitis and nasopharyngitis (each 21.4%). Ten (8.9%) patients withdrew because of an adverse event. Renal function remained stable, and the frequency of emergent adverse events generally decreased over time. Conclusions Everolimus treatment remained safe and effective over approximately 4 years. The overall risk/benefit assessment supports the use of everolimus as a viable treatment option for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. Trial registration ClinicalTrials.gov NCT0079040

Microvascular inflammation is a risk factor in kidney transplant recipients with very late conversion from calcineurin inhibitor-based regimens to belatacept

Background: In de novo kidney transplant recipients (KTR) treatment with belatacept has been established as a comparable option as maintenance immunosuppression, preferably as a strategy to convert from calcineurin inhibitor (CNI)- to belatacept-based immunosuppression. Switch to belatacept demonstrated improved renal function in patients with CNI-induced nephrotoxicity, but risk of transplant rejection and the development of donor-specific antibodies (DSA) are still a matter of debate. Only few data are available in patients at increased immunological risk and late after transplantation. Methods: We analyzed 30 long-term KTR (including 2 combined pancreas-KTR) converted from CNI to belatacept > 60 months after transplantation with moderate to severe graft dysfunction (GFR ≤ 45 mL/min). Biopsies were classified according to the Banff 2015 criteria. Group differences were assessed in a univariate analysis using Mann Whitney U or Chi square test, respectively. Multivariate analysis of risk factors for treatment failure was performed using a binary logistic regression model including significant predictors from univariate analysis. Fifty-six KTR matched for donor and recipient characteristics were used as a control cohort remaining under CNI-treatment. Results: Patient survival in belatacept cohort at 12/24 months was 96.7%/90%, overall graft survival was 76.7 and 60.0%, while graft survival censored for death was 79.3%/66.7%. In patients with functioning grafts, median GFR improved from 22.5 mL/min to 24.5 mL/min at 24 months. Positivity for DSA at conversion was 46.7%. From univariate analysis of risk factors for graft loss, GFR < 25 mL/min (p = 0.042) and Banff microvascular inflammation (MVI) sum score ≥ 2 (p = 0.023) at conversion were significant at 24 months. In the analysis of risk factors for treatment failure, a MVI sum score ≥ 2 was significant univariately (p = 0.023) and in a bivariate (p = 0.037) logistic regression at 12 months. DSA-positivity was neither associated with graft loss nor treatment failure. The control cohort had comparable graft survival outcomes at 24 months, albeit without increase of mean GFR in patients with functioning grafts (ΔGFR of - 3.6 ± 8.5 mL/min). Conclusion: Rescue therapy with conversion to belatacept is feasible in patients with worsening renal function, even many years after transplantation. The benefit in patients with MVI and severe GFR impairment remains to be investigated

Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study

Objectives We examined the long-term effects of everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. Methods Following favorable results from the double-blind core phase of EXIST-2 (NCT00790400), patients were allowed to receive open-label everolimus (extension phase). Patients initially randomly assigned to everolimus continued on the same dose;those who were receiving placebo crossed over to everolimus 10 mg/day. Dose modifications were based on tolerability. The primary end point was angiomyolipoma response rate, defined as a >= 50% reduction from baseline in the sum volume of target renal angiomyolipomas in the absence of new target angiomyolipomas, kidney volume increase of >20% from nadir, and angiomyolipoma-related bleeding grade >= 2. The key secondary end point was safety. Results Of the 112 patients who received >= 1 dose of everolimus, 58% (95% CI, 48.3% to 67.3%) achieved angiomyolipoma response. Almost all patients (97%) experienced reduction in renal lesion volumes at some point during the study period. Median duration of everolimus exposure was 46.9 months. Sixteen (14.3%) patients experienced angiomyolipoma progression at some point in the study. No angiomyolipoma-related bleeding or nephrectomies were reported. One patient on everolimus underwent embolization for worsening right flank pain. Subependymal giant cell astrocytoma lesion response was achieved in 48% of patients and skin lesion response in 68% of patients. The most common adverse events suspected to be treatment-related were stomatitis (42%), hypercholesterolemia (30.4%), acne (25.9%), aphthous stomatitis and nasopharyngitis (each 21.4%). Ten (8.9%) patients withdrew because of an adverse event. Renal function remained stable, and the frequency of emergent adverse events generally decreased over time. Conclusions Everolimus treatment remained safe and effective over approximately 4 years. The overall risk/benefit assessment supports the use of everolimus as a viable treatment option for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis

Long-term follow up after kidney transplantation - risk factors for late graft loss

Eine qualifizierte und regelmäßige Nachsorge ist nach NTx unverzichtbar, denn hiervon hängen Patienten- und Transplantatüberleben ab. Trotz differenzierter Leitlinien, die eine Vielzahl von klinischen Besonderheiten nach NTx behandeln, gibt es bisher nur wenige Studien, die diese Handlungsempfehlungen untermauern. Die vorgestellten Arbeiten befassen sich mit besonderen klinischen Fragestellungen nach NTx und zeigen Besonderheiten dieses Settings auf.Long-term graft survival after kidney transplantation is dependent on specialized continuous follow-up care. Current guidelines refer to a limited number of clinical studies, supporting the need for more long-term clinical follow-up studies. The manuscript presented in the thesis all focus on the clinical setting after kidney transplantation

Long-term follow up after kidney transplantation - risk factors for late graft loss

Eine qualifizierte und regelmäßige Nachsorge ist nach NTx unverzichtbar, denn hiervon hängen Patienten- und Transplantatüberleben ab. Trotz differenzierter Leitlinien, die eine Vielzahl von klinischen Besonderheiten nach NTx behandeln, gibt es bisher nur wenige Studien, die diese Handlungsempfehlungen untermauern. Die vorgestellten Arbeiten befassen sich mit besonderen klinischen Fragestellungen nach NTx und zeigen Besonderheiten dieses Settings auf.Long-term graft survival after kidney transplantation is dependent on specialized continuous follow-up care. Current guidelines refer to a limited number of clinical studies, supporting the need for more long-term clinical follow-up studies. The manuscript presented in the thesis all focus on the clinical setting after kidney transplantation

Treatment effect of mTOR-inhibition on tissue composition of renal angiomyolipomas in tuberous sclerosis complex (TSC).

Tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML) have a high lifetime risk of acute bleeding. MTOR-inhibitors are a promising novel treatment for TSC-AML, however adequate response to therapy can be difficult to assess. Early changes in MRI signal may serve as a novel early indicator for a satisfactory response to mTOR-inhibitor therapy of AML.Thirty-eight patients with the definite diagnosis of tuberous sclerosis receiving everolimus therapy and n = 19 patients without specific therapy were included. 1.5 Tesla MRI was performed including sequences with a selective fat suppression. Patients were investigated prior to the initiation of therapy (baseline) and after 0.05) and size (p>0.05) were measured in the control group.mTOR inhibitor therapy in TSC patients results in an early and pronounced fatty transformation of AMLs on MRI. Fatty transformation could represent a novel early indicator of response to therapy in this patient collective