Intrarenal Doppler ultrasonography in patients with HFrEF and acute decompensated heart failure undergoing recompensation.

OBJECTIVES: Renal venous congestion due to backward heart failure leads to disturbance of renal function in acute decompensated heart failure (ADHF). Whether decongestion strategies have an impact on renal venous congestion is unknown. Objective was to evaluate changes in intrarenal hemodynamics using intrarenal Doppler ultrasonography (IRD) in patients with heart failure with reduced ejection fraction (HFrEF) and ADHF undergoing recompensation. METHODS: Prospective observational study in patients with left ventricular ejection fraction (LV-EF) ≤ 35% hospitalized due to ADHF. IRD measurement was performed within the first 48 h of hospitalisation and before discharge. Decongestion strategies were based on clinical judgement according to heart failure guidelines. IRD was used to assess intrarenal venous flow (IRVF) pattern, venous impedance index (VII) and resistance index (RI). Laboratory analyses included plasma creatinine, eGFR and albuminuria. RESULTS: A number of 35 patients with ADHF and LV-EF ≤ 35% were included into the study. IRD could be performed in 30 patients at inclusion and discharge. At discharge, there was a significant reduction of VII from a median of 1.0 (0.86-1.0) to 0.59 (0.26-1.0) (p < 0.01) as well as improvement of IRVF pattern categories (p < 0.05) compared to inclusion. Albuminuria was significantly reduced from a median of 78 mg/g creatinine (39-238) to 29 mg/g creatinine (16-127) (p = 0.02) and proportion of patients with normoalbuminuria increased (p = 0.01). Plasma creatinine and RI remained unchanged (p = 0.73; p = 0.43). DISCUSSION: This is the first study showing an effect of standard ADHF therapy on parameters of renal venous congestion in patients with HFrEF and ADHF. Doppler sonographic evaluation of renal venous congestion might provide additional information to guide decongestion strategies in patients with ADHF.

Discrepancies Between Osteoporotic Fracture Evaluations in Men Based on German (DVO) Osteoporosis Guidelines or the FRAX Score.

INTRODUCTION: Established scores estimate 10-year fracture risk in osteoporosis to assist with treatment recommendations. This study compared the risk probabilities of major osteoporotic and hip fractures calculated by the FRAX tool with those of the DVO score, established in German-speaking countries. MATERIAL AND METHODS: This seven-year retrospective study analyzed data of 125 male patients (mean age: 59.2±10.7 years) evaluated for osteoporosis. For the DVO score, the therapy threshold of>30% for vertebral and hip fractures suggested by DVO guidelines was implemented. We calculated fracture risks based on FRAX scores with aBMD and applied a common therapy threshold of≥3% for hip fracture and subsequently determined the "DVO-equivalent risk level" for FRAX-based assessment that would identify as many male patients as identified by the DVO score. RESULTS: Based on DVO score, 60.0% of patients had a 10-year risk of hip and vertebral fractures>30%. The recommendations for individuals based on FRAX scores for hip fracture with aBMD with risk≥3% overlapped with those based on DVO score in 36% of patients. Patients identified for treatment only by DVO score presented a higher percentage of spine fractures (65 vs. 41%). The thresholds for this "DVO-equivalent risk level" for 'FRAX with aBMD' was estimated to be≥6.7% for major osteoporotic fracture and≥2.1% for hip fracture.This study demonstrates that the DVO score was more sensitive than the FRAX score for patients with prevalent spinal fractures. We suggest considering the appropriate score and therapy threshold carefully in the daily care of male patients.

COVID-19 vaccination strategy for hospital staff in Germany: a cross-sectional study in March-April 2021.

BACKGROUND: SARS-CoV-2 vaccination for healthcare workers (HCWs) started in Germany in December 2020. Hospitals had little time to prepare a vaccination strategy. AIM: To gather information on the initial vaccination strategy for HCWs from the infection control practitioners in Germany. METHODS: A cross-sectional, ethically approved questionnaire was developed, formatted as an online survey and pre-tested. Infection control practitioners responsible for hygiene/infection prevention in 987 randomly selected German hospitals were invited to participate in the survey in March and April 2021. For statistical analysis, the hospitals were categorized into two groups based on bed capacity (<500 beds: small; ≥500 beds: large). FINDINGS: One hundred out of 987 (10%) infection control practitioners completed the survey. In 80% of the participating hospitals, HCW vaccination prioritization was based on recommendations of the German standing committee on vaccination (STIKO). Even so, only 54% prioritized the vaccination of HCWs with contact to vulnerable patients, thus deviating from STIKO recommendations. HCWs with a high personal health risk were prioritized for vaccination in 24% of the hospitals. Transferring unvaccinated HCWs to an area with less infection risk was considered by 2% of large and 12% of small hospitals. CONCLUSION: Vaccination prioritization differed across hospitals and deviated from STIKO recommendations. A pandemic preparedness concept should address the potential impact of divergent strategies compared to a common approach. In addition, further studies analysing the reasons why HCWs remain unvaccinated are needed to adopt effective strategies. This is especially important against the background of facility-based compulsory vaccination.

Infection control strategies for patients and accompanying persons during the COVID-19 pandemic in German hospitals: a cross-sectional study in March-April 2021.

BACKGROUND: Patients are at risk of nosocomial COVID-19 infection. The role of accompanying persons/visitors as potential infection donors is not yet well researched, but the risk will be influenced by prevention measures recommended by infection control practitioners. AIM: To collect information about COVID-19 infection control strategies for patients and accompanying persons from infection control practitioners in German hospitals. METHODS: A cross-sectional questionnaire was developed, ethically approved, pre-tested and formatted as an online tool. Infection control practitioners in 987 randomly selected German hospitals were invited to participate in March and April 2021. For statistical analysis, the hospitals were categorized as small (0-499 beds) or large (≥500 beds). FINDINGS: One hundred surveys were completed (response rate: 10%). A higher proportion of large (71%) than small (49%) hospitals let patients decide freely whether to wear medical or FFP2 masks. Most hospitals reported spatial separation for COVID-19 patients and non-COVID-19 cases (38%) or additionally for suspected COVID-19 cases (53%). A separation of healthcare teams for these areas existed in 54% of the hospitals. Accompaniment bans were more prevalent in large (52%) than in small hospitals (29%), but large hospitals granted more exemptions. CONCLUSION: The decision as to whether to separate areas and teams seemed to depend on the hospital's structural conditions, therefore impairing the implementation of recommendations. Accompaniment regulations differ between hospital sizes and may depend on patient numbers, case type/severity and patients' requirements. In the dynamic situation of a pandemic, it can be difficult to stay up to date with findings and recommendations on infection control.

Retrospective study on risk factors for repeated dental treatment of children under general anaesthesia.

AIM: This retrospective study aimed to evaluate potential risk factors predicting repeated dental treatment of children under general anaesthesia. MATERIALS AND METHODS: Children below 12 years of age receiving at least one dental treatment under general anaesthesia between 03/2010 and 10/2018 were analysed (n = 935, mean age: 4.6 ± 2.4). Dental records were analysed retrospectively for anamnestic, demographic, oral health and treatment factors. Kaplan-Meier statistics was used to estimate the time to second dental treatment under general anaesthesia. Potential risk factors for repeated dental treatment underwent univariate analysis using log-rank tests and were then submitted to a multi-variate Cox-regression analysis (a = 5%). RESULTS: One hundred fifteen children (12.3%) received or were planned to receive repeated dental treatment under general anaesthesia. In children receiving repeated dental treatment, the time intervals between first and second general anaesthesia and second and third general anaesthesia amounted to 22 ± 18 and 23 ± 20 months, respectively. The use of fluoridated toothpaste (HR: 0.28, p < 0.01) and attending 2 or more recall appointments per year (HR: 0.6, p < 0.01) significantly decreased the risk for repeated dental treatment under general anaesthesia in the multivariate model. CONCLUSION: Adherence to preventive recall appointments and to oral hygiene recommendations is essential to maintain oral health and avoid repeated dental treatment under general anaesthesia.

Clinical Evaluation of Chairside-Fabricated Partial Crowns Made of Zirconia- Reinforced Lithium Silicate Ceramic - 2-Year-Results.

INTRODUCTION: In a prospective study, the clinical performance of chairside-fabricated partial-crowns made of zirconia-reinforced lithiumsilicate (ZLS)-ceramic was evaluated after 2 years. MATERIALS AND METHODS: 45 patients (28 female/17 male) underwent restoration with 61 chairside-fabricated ZLS partial-crowns on vital premolars and molars. In variation from the manufacturer's recommendations (minimum material thickness (MMT)=1.0 mm), partial-crowns with reduced material thicknesses were fabricated: group 1, MMT=0.5-0.74 mm (n=31); group 2, MMT=0.75-1.0 mm (n=30). The restorations were luted with either a self-adhesive cement (SAC) or the total-etch technique using a dual-curing composite cement (DC). The MMT and cementation technique (SAC vs. DC) were evaluated as possible covariates of the time-dependent survival (SVR) and success rate (SCR) using univariate log-rank-tests. RESULTS: Forty-four patients with 59 restorations participated in the 2-year follow-up examinations. In group 1 (n=31), there were 2 losses due to ceramic fracture (SVR: 94.0% (95% confidence interval (CI): 0.85-1)). In group 2, no losses were documented (SVR: 100%). In 2 restorations cemented with SAC, recementation was necessary (overall SCR: 93% (CI: 0.87-1)). CONCLUSION: To avoid early material-related fractures, observing the recommended minimum thickness of 1.0 mm is essential. However, further validation of these results in studies with longer observational periods is required.

Comprehensive identification of genes driven by ERV9-LTRs reveals TNFRSF10B as a re-activatable mediator of testicular cancer cell death.

The long terminal repeat (LTR) of human endogenous retrovirus type 9 (ERV9) acts as a germline-specific promoter that induces the expression of a proapoptotic isoform of the tumor suppressor homologue p63, GTAp63, in male germline cells. Testicular cancer cells silence this promoter, but inhibitors of histone deacetylases (HDACs) restore GTAp63 expression and give rise to apoptosis. We show here that numerous additional transcripts throughout the genome are driven by related ERV9-LTRs. 3' Rapid amplification of cDNA ends (3'RACE) was combined with next-generation sequencing to establish a large set of such mRNAs. HDAC inhibitors induce these ERV9-LTR-driven genes but not the LTRs from other ERVs. In particular, a transcript encoding the death receptor DR5 originates from an ERV9-LTR inserted upstream of the protein coding regions of the TNFRSF10B gene, and it shows an expression pattern similar to GTAp63. When treating testicular cancer cells with HDAC inhibitors as well as the death ligand TNF-related apoptosis-inducing ligand (TRAIL), rapid cell death was observed, which depended on TNFRSF10B expression. HDAC inhibitors also cooperate with cisplatin (cDDP) to promote apoptosis in testicular cancer cells. ERV9-LTRs not only drive a large set of human transcripts, but a subset of them acts in a proapoptotic manner. We propose that this avoids the survival of damaged germ cells. HDAC inhibition represents a strategy of restoring the expression of a class of ERV9-LTR-mediated genes in testicular cancer cells, thereby re-enabling tumor suppression.

Interactions of human MSC with head and neck squamous cell carcinoma cell line PCI-13 reduce markers of epithelia-mesenchymal transition.

OBJECTIVES: Cancer progression is influenced by tumor microenvironment and communication of stromal cells and tumor cells. Interactions may enhance epithelial-mesenchymal transition (EMT) of tumor cells through signaling proteins such as Wnt/beta-catenin and matrix metalloproteinases (MMP), as well as loss of cellular integrity, which affects invasion, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC). In this study, we are testing the hypothesis that interactions of human mesenchymal stromal cells (MSCs) with HNSCC might influence the expression of markers of EMT and tumor progression by co-culturing human MSC with the PCI-13 HNSCC line. MATERIALS AND METHODS: Pooled MSCs were derived from the iliac bone marrow of seven patients and co-cultured in transwell permeable membrane wells with tumor cells of the established HNSCC cell line PCI-13 (UICC: T3, N1, M0). MSCs were characterized through fluorescence-activated cell sorting (FACS) analysis. Expression of Wnt3, E-cadherin, beta-catenin, MMP14, cathepsin b, and ETS1 was assessed by quantitative RT-PCR. RESULTS: We were able to show that co-culture of MSCs and PCI-13 leads to a significantly reduced expression of Wnt3, MMP14, and beta-catenin compared to controls, whereas the expression of cathepsin b and ETS1 was not significantly different between co-cultures and controls. CONCLUSION: Our results suggest that the interaction between MSCs and PCI-13 may suppress EMT in cancer cells. CLINICAL RELEVANCE: The influence of MSCs can suppress the onset of EMT in HNSCC, affecting tumor progression and therapy.

Improvement of renal graft function after conversion from a calcineurin inhibitor including immunosuppression to a mycophenolate sodium including regimen: a 4-year follow-up.

BACKGROUND: The most common immunosuppressive regimens after renal transplantation include calcineurin inhibitors (CNI). However, due to renal toxicity long-term graft survival does not seem to be positively affected by CNIs. METHODS: In the present study, we investigated 17 patients, in which the CNI immunosuppression was converted to a CNI-free, mycophenolate sodium (MPS) regimen. Conversion was performed due to progressive impairment of the graft function from suspected CNI toxicity. We retrospectively analyzed graft function as well as toxicity and surrogate markers for 4 years before and 4 years after conversion using a repeated-measures mixed model data analysis and/or a paired sample t-test. RESULTS: The mean time point of therapy conversion was 11.2 ± 4.6 years after transplantation. Within 1 month of CNI discontinuation, allograft function improved significantly, remaining at a significant level for 2 years. The estimated glomerular filtration rate increased from 43.4 ± 14.8 to a maximum of 55.7 ± 21.7 mL/min at 1 year after conversion (P = .0027). After 4 years, the end of the observation period, renal function was similar to the baseline. There were no significant side effects. CONCLUSION: These data suggested that, when chronic CNI-toxicity is suspected, renal allograft recipients may benefit from CNI withdrawal in favor of a MPS-including immunosuppressive regimen.