Advanced diffusion MRI provides evidence for altered axonal microstructure and gradual peritumoral infiltration in GBM in comparison to brain metastases.

PURPOSE: In contrast to peritumoral edema in metastases, GBM is histopathologically characterized by infiltrating tumor cells within the T2 signal alterations. We hypothesized that depending on the distance from the outline of the contrast-enhancing tumor we might reveal imaging evidence of gradual peritumoral infiltration in GBM and predominantly vasogenic edema around metastases. We thus investigated the gradual change of advanced diffusion metrics with the peritumoral zone in metastases and GBM. METHODS: In 30 patients with GBM and 28 with brain metastases, peritumoral T2 hyperintensity was segmented in 33% partitions based on the total volume beginning at the enhancing tumor margin and divided into inner, middle and outer zones. Diffusion Tensor Imaging (DTI)-derived fractional anisotropy and mean diffusivity as well as Diffusion Microstructure Imaging (DMI)-based parameters Dax-intra, Dax-extra, V­CSF and V-intra were employed to assess group-wise differences between inner and outer zones as well as within-group gradients between the inner and outer zones. RESULTS: In metastases, fractional anisotropy and Dax-extra were significantly reduced in the inner zone compared to the outer zone (FA p = 0.01; Dax-extra p = 0.03). In GBM, we noted a reduced Dax-extra and significantly lower intraaxonal volume fraction (Dax-extra p = 0.008, V­intra p = 0.006) accompanied by elevated axial intraaxonal diffusivity in the inner zone (p = 0.035). Between-group comparison of the outer to the inner zones revealed significantly higher gradients in metastases over GBM for FA (p = 0.04) as well as the axial diffusivity in the intra- (p = 0.02) and extraaxonal compartment (p < 0.001). CONCLUSION: Our findings provide evidence of gradual alterations within the peritumoral zone of brain tumors. These are compatible with predominant (vasogenic) edema formation in metastases, whereas our findings in GBM are in line with an axonal destructive component in the immediate peritumoral area and evidence of tumor cell infiltration with accentuation in the tumor's vicinity.

Rationale and design of the iCORONARY trial: improving the cost-effectiveness of coronary artery disease diagnosis.

BACKGROUND: In patients with stable coronary artery disease (CAD), revascularisation decisions are based mainly on the visual grading of the severity of coronary stenosis on invasive coronary angiography (ICA). However, invasive fractional flow reserve (FFR) is the current standard to determine the haemodynamic significance of coronary stenosis. Non-invasive and less-invasive imaging techniques such as computed-tomography-derived FFR (FFR-CT) and angiography-derived FFR (QFR) combine both anatomical and functional information in complex algorithms to calculate FFR. TRIAL DESIGN: The iCORONARY trial is a prospective, multicentre, non-inferiority randomised controlled trial (RCT) with a blinded endpoint evaluation. It investigates the costs, effects and outcomes of different diagnostic strategies to evaluate the presence of CAD and the need for revascularisation in patients with stable angina pectoris who undergo coronary computed tomography angiography. Those with a Coronary Artery Disease-Reporting and Data System (CAD-RADS) score between 0-2 and 5 will be included in a prospective registry, whereas patients with CAD-RADS 3 or 4A will be enrolled in the RCT. The RCT consists of three randomised groups: (1) FFR-CT-guided strategy, (2) QFR-guided strategy or (3) standard of care including ICA and invasive pressure measurements for all intermediate stenoses. The primary endpoint will be the occurrence of major adverse cardiac events (death, myocardial infarction and repeat revascularisation) at 1 year. CLINICALTRIALS: gov-identifier: NCT04939207. CONCLUSION: The iCORONARY trial will assess whether a strategy of FFR-CT or QFR is non-inferior to invasive angiography to guide the need for revascularisation in patients with stable CAD. Non-inferiority to the standard of care implies that these techniques are attractive, less-invasive alternatives to current diagnostic pathways.

Impact of Time of Surgery on the Outcome after Surgical Stabilization of Rib Fractures in Severely Injured Patients with Severe Chest Trauma-A Matched-Pairs Analysis of the German Trauma Registry.

Purpose: In severely injured patients with multiple rib fractures, the beneficial effect of surgical stabilization is still unknown. The existing literature shows divergent results, and the indication and especially the right timing of an operation are the subject of a broad discussion. The aim of this study was to determine the influence of the time point of surgical stabilization of rib fractures (SSRF) on the outcome in a multicenter database with special regard to the duration of ventilation, intensive care, and overall hospital stay. Methods: Data from the TraumaRegister DGU collected between 2010 and 2019 were used to evaluate patients above 16 years of age with severe rib fractures [Abbreviated Injury Score (AIS) ≥ 3] who received an SSRF in a matched-pairs analysis. In this matched-pairs analysis, we compared the effects of an early SSRF within 48 h after initial trauma vs. late SSRF 3-10 days after trauma. Results: After the selection process, we were able to find 142 matched pairs for further evaluation. Early SSRF was associated with a significantly shorter length of stay in the intensive care unit (16.2 days vs. 12.7 days, p = 0.020), and the overall hospital stay (28.5 days vs. 23.4 days, p = 0.005) was significantly longer in the group with late SSRF. Concerning the days on mechanical ventilation, we were able to demonstrate a trend for an approximately 1.5 day shorter ventilation time for patients after early SSRF, although this difference was not statistically significant (p = 0.226). Conclusions: We were able to determine the significant beneficial effects of early SSRF resulting in a shorter intensive care unit stay and a shorter length of stay in hospital and additionally a trend to a shorter time on mechanical ventilation.

MRI biomarker of muscle composition is associated with severity of pelvic organ prolapse.

BACKGROUND: The pathophysiology of pelvic organ prolapse is largely unknown. We hypothesized that reduced muscle mass on magnetic resonance defecography (MRD) is associated with increased pelvic floor laxity. The aim of this study was to compare the psoas and puborectalis muscle mass composition and cross-sectional area among patients with or without pelvic laxity. METHODS: An observational retrospective study was conducted on women > age 18 years old who had undergone MRD for pelvic floor complaints from January 2020 to December 2020 at Stanford Pelvic Health Center. Pelvic floor laxity, pelvic organ descent, and rectal prolapse were characterized by standard measurements on MRD and compared to the psoas (L4 level) and puborectalis muscle index (cross-sectional area adjusted by height) and relative fat fraction, quantified by utilizing a 2-point Dixon technique. Regression analysis was used to quantify the association between muscle characteristics and pelvic organ measurements. RESULTS: The psoas fat fraction was significantly elevated in patients with abnormally increased resting and strain H and M lines (p < 0.05) and increased with rising grades of Oxford rectal prolapse (p = 0.0001), uterovaginal descent (p = 0.001) and bladder descent (p = 0.0005). In multivariate regression analysis, adjusted for age and body mass index, the psoas fat fraction (not muscle index) was an independent risk factor for abnormal strain H and M line; odds ratio (95% confidence interval) of 17.8 (2-155.4) and 18.5 (1.3-258.3) respectively, and rising Oxford grade of rectal prolapse 153.9 (4.4-5383) and bladder descent 12.4 (1.5-106). Puborectalis fat fraction was increased by rising grades of Oxford rectal prolapse (p = 0.0002). CONCLUSIONS: Severity of pelvic organ prolapse appears to be associated with increasing psoas muscle fat fraction, a biomarker for reduced skeletal muscle mass. Future prospective research is needed to determine if sarcopenia may predict postsurgical outcomes after pelvic organ prolapse repair.

Percutaneous Transsplenic Balloon-Assisted Transjugular Intrahepatic Portosystemic Shunt Placement in Patients with Portal Vein Obliteration for Portal Vein Recanalization: Feasibility, Safety and Effectiveness.

PURPOSE: To assess the feasibility, safety and effectiveness of portal vein recanalization (PVR)-transjugular portosystemic shunt (TIPS) placement via splenic access using a balloon puncture technique. MATERIALS AND METHODS: In a single-center retrospective study from March 2017 to February 2021, 14 consecutive patients with portal hypertension, chronic liver disease and portal vein occlusion or near-complete (> 95%) occlusion were referred for PVR-TIPS placement. Feasibility, safety and effectiveness including procedural characteristics such as technical success, complication profile and splenic access time (SAT), balloon positioning time (BPT), conventional portal vein entry time (CPVET), overall procedure time (OPT), fluoroscopy time (FT), dose-area product (DAP) and air kerma (AK) were evaluated. RESULTS: Transsplenic PVR-TIPS using balloon puncture technique was technically feasible in 12 of 14 patients (8 men, 49 ± 13 years). In two patients without detectable intrahepatic portal vein branches, TIPS placement was not feasible and both patients were referred for further treatment with nonselective beta blockers and endoscopic variceal ligation. No complications grade > 3 of the Cardiovascular and Interventional Radiological Society of Europe classification system occurred. The SAT was 25 ± 21 min, CPVET was 33 ± 26 min, the OPT was 158 ± 54 min, the FT was 42 ± 22 min, the DAP was 167.84 ± 129.23 Gy*cm2 and the AK was 1150.70 ± 910.73 mGy. CONCLUSIONS: Transsplenic PVR-TIPS using a balloon puncture technique is feasible and appears to be safe in our series of patients with obliteration of the portal vein. It expands the interventional options in patients with chronic PVT.

Adrenal venous sampling in primary hyperaldosteronism: correlation of hormone indices and collimated C-arm CT findings.

PURPOSE: To evaluate the feasibility and effect of an approach to adrenal venous sampling (AVS) analysis by combining established selective cortisol and aldosterone indices with the acquisition of a collimated C-arm CT(CACTColl). METHODS: Overall, 107 consecutive patients (45f,62 m; 54 ± 10 years) undergoing 111 AVS procedures without hormonal stimulation from 7/13 to 2/20 in a single institution were retrospectively analysed. Hormone levels were measured in sequential samples of the suspected adrenal veins and right iliac vein, and selectivity indices (SI) computed. Stand-alone SICortisol and/or SIAldosterone ≥ 2.0 as well as SICortisol and/or SIAldosterone ≥ 1.1 combined with positive right-sided CACTColl of the adrenals (n = 80; opacified right adrenal vein) were defined as a successful AVS procedure. Radiation exposure of CACT was measured via dose area product (DAP) and weighed against an age-/weight-matched cohort (n = 66). RESULTS: Preliminary success rates (SICortisol and/or SIAldosterone ≥ 2.0) were 99.1% (left) and 72.1% (right). These could be significantly increased to a 90.1% success rate on the right, by combining an adjusted SI of 1.1 with a positive CACTColl proving the correct sampling position. Sensitivity for stand-alone collimated CACT (CACTColl) was 0.93, with 74/80 acquired CACTColl confirming selective cannulation by adrenal vein enhancement. Mean DAPColl_CACT measured 2414 ± 958 µGyxm2, while mean DAPFull-FOV_CACT in the matched cohort measured 8766 ± 1956 µGyxm2 (p < 0.001). CONCLUSION: Collimated CACT in AVS procedures is feasible and leads to a significant increase in success rates of (right-sided) selective cannulation and may in combination with adapted hormone indices, offer a successful alternative to previously published AVS analysis algorithms with lower radiation exposure compared to a full-FOV CACT.

Two-dimensional parametric parenchymal blood flow in transarterial chemoembolisation for hepatocellular carcinoma: perfusion change quantification and tumour response prediction at 3 months post-intervention.

AIM: To evaluate the feasibility and potential value of two-dimensional (2D) parametric parenchymal blood flow (2D-PPBF) for the assessment of perfusion changes during transarterial chemoembolisation with drug-eluting beads (DEB-TACE) and to analyse correlations of 2D-PPBF parameters and tumour response. MATERIALS AND METHODS: Thirty-two patients (six women, 26 men, mean age: 67±8.9 years) with unresectable hepatocellular carcinoma (HCC) who underwent their first DEB-TACE were included in this study. To quantify perfusion changes using 2D-PPBF, the acquired digital subtraction angiography (DSA) series were post-processed. Ratios were calculated between the reference region of interest (ROI) and the wash-in rate (WIR), the arrival to peak (AP) and the area under the curve (AUC) of the generated time-density curves. Comparisons between pre- and post-embolisation data were made using the Wilcoxon signed-rank test. Tumour response was assessed at 3 months using the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and correlated to changes of 2D-PPBF parameters. RESULTS: All 2D-PPBF parameters derived from the ROI-based time-attenuation curves were significantly different pre-versus post-DEB-TACE. Although the AUC, the WIR and target lesion size measured in accordance with mRECIST decreased (p≤0.0001) significantly, AP values showed a significant increase (p = 0.0033). Tumour response after DEB-TACE correlated with changes in the AUC (p = 0.01, r = -0.45). CONCLUSION: 2D-PPBF offers an objective approach to analyse perfusion changes of embolised tumour tissue following DEB-TACE and can therefore be used to predict tumour response.

Percutaneous isolated hepatic perfusion (chemosaturation) with melphalan following right hemihepatectomy in patients with cholangiocarcinoma and metastatic uveal melanoma: peri- and post-interventional adverse events and therapy response compared to a matched group without prior liver surgery.

To evaluate feasibility, frequency and severity of peri-procedural complications and post-procedural adverse events (AEs) in patients with advanced cholangiocarcinoma or liver metastasis of uveal melanoma and prior hemihepatectomy undergoing chemosaturation percutaneous hepatic perfusion (CS-PHP) and to analyze therapy response and overall survival compared to a matched group without prior surgery. CS-PHP performed between 10/2014 and 02/2018 were retrospectively assessed. To determine peri-procedural safety and post-procedural adverse events, hospital records and hematological, hepatic and biliary function were categorized using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (1-5; mild-death). Significance was tested using Wilcoxon signed-rank and Mann-Whitney U test. Kaplan-Meier estimation and log-rank test assessed survival. Overall 21 CS-PHP in seven patients (4/7 males; 52 ± 10 years) with hemihepatectomy (grouphemihep) and 22 CS-PHP in seven patients (3/7 males; 63 ± 12 years) without prior surgery (groupnoresection) were included. No complications occurred during the CS-PHP procedures. Transient changes (CTCAE grade 1-2) of liver enzymes and blood cells followed all procedures. In comparison, grouphemihep presented slightly more AEs grade 3-4 (e.g. thrombocytopenia in 57% (12/21) vs. 41% (9/22; p = 0.37)) 5-7 days after CS-PHP. These AEs were self-limiting or responsive to treatment (insignificant difference of pre-interventional to 21-45 days post-interventional values (p > 0.05)). One patient in grouphemihep with high tumor burden died eight days following CS-PHP. No deaths occurred in groupnoresection. In comparison, overall survival after first diagnosis was insignificantly shorter in groupnoresection (44.7(32-56.1) months) than in grouphemihep (48.3(34.6-72.8) months; p = 0.48). The severity of adverse events following CS-PHP in patients after hemihepatectomy was comparable to a matched group without prior liver surgery. Thus, the performance of CS-PHP is not substantially compromised by a prior hemihepatectomy.

A randomised trial comparing a brief online delivery of mindfulness-plus-values versus values only for symptoms of depression: Does baseline severity matter?

BACKGROUND: Acceptance/mindfulness-based interventions often focus on (a) developing dispositional mindfulness and (b) pursuing personally meaningful and valued activities. Acceptance/mindfulness-based interventions can reduce depression, but little is known about the combined effects of components or the influence of baseline variables on outcomes. This study tested whether practicing a brief (10-min) mindfulness meditation over a 2-week period followed by a single values session (mindfulness+values) was more effective than values alone (values only) in reducing symptoms of depression. The study was delivered online and modules were fully self-help (i.e., no therapist contact). METHODS: 206 participants (Mage=23.4 years, SD=6.53) with elevated depression scores (DASS-depression ≥ 10) were randomised to: mindfulness+values condition or a 2-week wait period followed by the values session (i.e., values only condition). Symptoms of depression were assessed at baseline, after the 2-week mindfulness practice/wait period, and 1-week following the values session. RESULTS: Reductions in depression and recovery rates were significantly greater following mindfulness+values than values only. Baseline severity affected outcomes: mindfulness+values was significantly more beneficial than values only for individuals with high baseline levels of depression. Outcomes did not differ for those with low levels of depression. Rates of deterioration were higher than expected for values only participants. LIMITATIONS: Conclusions are preliminary and tentative due to no follow-up period and a small sample. Drop-out was high (50%) and findings cannot be assumed to generalise to treatment seeking or more diverse samples. CONCLUSIONS: Tentatively, results suggest mindfulness+values can significantly reduce depression, especially for individuals with higher baseline depression.

Transjugular intrahepatic portosystemic shunt placement: portal vein puncture guided by 3D/2D image registration of contrast-enhanced multi-detector computed tomography and fluoroscopy.

BACKGROUND: To assess the technical feasibility, success rate, puncture complications and procedural characteristics of transjugular intrahepatic portosystemic shunt (TIPS) placement using a three-dimensional vascular map (3D-VM) overlay based on image registration of pre-procedural contrast-enhanced (CE) multi-detector computed tomography (MDCT) for portal vein puncture guidance. MATERIALS AND METHODS: Overall, 27 consecutive patients (59 ± 9 years, 18male) with portal hypertension undergoing elective TIPS procedure were included. TIPS was guided by CE-MDCT overlay after image registration based on fluoroscopic images. A 3D-VM of the hepatic veins and the portal vein was created based on the pre-procedural CE-MDCT and superimposed on fluoroscopy in real-time. Procedural characteristics as well as hepatic vein catheterization time (HVCT), puncture time (PT), overall procedural time (OPT), fluoroscopy time (FT) and the dose area product (DAP) were evaluated. Thereafter, HVCT, PT, OPT and FT using 3D-VM (61 ± 9 years, 14male) were compared to a previous using classical fluoroscopic guidance (53 ± 9 years, 21male) for two interventional radiologist with less than 3 years of experience in TIPS placement. RESULTS: All TIPS procedure using of 3D/2D image registered 3D-VM were successful with a significant reduction of the PSG (p < 0.0001). No clinical significant complication occurred. HVCT was 14 ± 11 min, PT was 14 ± 6 min, OPT was 64 ± 29 min, FT was 21 ± 12 min and DAP was 107.48 ± 93.84 Gy cm2. HVCT, OPT and FT of the interventionalist with less TIPS experience using 3D/2D image registered 3D-VM were statistically different to an interventionalist with similar experience using fluoroscopic guidance (pHVCT = 0.0022; pOPT = 0.0097; pFT = 0.0009). PT between these interventionalists was not significantly different (pPT = 0.2905). CONCLUSION: TIPS placement applying registration-based CE-MDCT vessel information for puncture guidance is feasible and safe. It has the potential to improve hepatic vein catherization, portal vein puncture and radiation exposure.

Hypertension Is Associated with White Matter Disruption in Apparently Healthy Middle-Aged Individuals.

BACKGROUND AND PURPOSE: Traditional cardiovascular risk factors have been associated with white matter disease. Because hypertension results in vascular stiffness and impaired cerebral perfusion, we hypothesized that it would be the most relevant risk factor for microstructural white matter disruption in apparently healthy middle-aged individuals with a family history of early-onset coronary artery disease. MATERIALS AND METHODS: This was a cross-sectional analysis of participants in the Genetic Study of Atherosclerosis Risk with DTI. Regional fractional anisotropy of 181 segmented brain regions was measured using Eve WM Atlas. Risk factors were examined using univariate analysis for 48 regions representing deep WM structures. Minimal multivariable linear regression models adjusting for age, sex, and race and maximal linear regression models adjusting for cardiovascular risk factors were performed for regions meeting the Bonferroni threshold in the initial analysis. RESULTS: Included were 116 subjects (mean age, 49 ± 11 years; 57% men) with a moderate load of cardiovascular risk factors. Subjects with hypertension had significantly lower regional fractional anisotropy in the right cingulum and left stria terminalis in the minimal and maximal regression models. Additionally, there was lower regional fractional anisotropy in the left fornix in the maximal model and right sagittal stratum in the minimal model. Systolic blood pressure values were significantly associated with regional fractional anisotropy in the left superior longitudinal fasciculus in the maximal model. There were no significant differences among regional fractional anisotropy values for other cardiovascular risk factors. CONCLUSIONS: In middle-aged apparently healthy individuals with susceptibility to vascular disease, among all known cardiovascular risk factors, hypertension was associated with microstructural WM disruption.

[Optimization of criteria for activation of trauma teams : Avoidance of overtriage and undertriage]. / Optimierung der Kriterien zur Schockraumalarmierung : Vermeidung von Über- und Untertriage.

INTRODUCTION: Severely injured patients are supposed to be admitted to hospital via the trauma room. Appropriate criteria are contained in the S3 guidelines on the treatment of patients with severe/multiple injuries (S3-GL); however, some of these criteria require scarce hospital resources while the patients then often clinically present as uninjured. There are tendencies to streamline the trauma team activation criteria (TTAC); however, additional undertriage must be avoided. A study group of the emergency, intensive care medicine and treatment of the severely injured section (NIS) is in the process of optimizing the TTAC for the German trauma system. MATERIAL AND METHODS: In order to solve the objective the following multi-step approach is necessary: a) definition of patients who potentially benefit from TTA, b) verification of the definition in the TraumaRegister DGU® (TR-DGU), c) carrying out a prospective, multicenter study in order to determine overtriage and undertriage, thereby validating the activation criteria and d) revision of the current TTAC. RESULTS: This article summarizes the consensus criteria of the group assumed to be capable of identifying patients who potentially benefit from TTA. These criteria are used to test if TTA was justified in a specific case; however, as the TTCA of the S3-GL are not fully incorporated into the TR-DGU dataset and because cases must also be considered which were not subject to trauma room treatment and therefore were not included in the TR-DGU, it is necessary to perform a prospective full survey of all individuals in order to be able to measure overtriage and undertriage. CONCLUSION: Currently, the TR-DGU can only provide limited evidence on the quality of the TTAC recommended in Germany. This problem has been recognized and will be solved by conducting a prospective DGU-supported study, the results of which can be used to improve the TR-DGU dataset in order to enable further considerations on the quality of care (e. g. composition and size of the trauma team).

Swimming exercise demonstrates advantages over running exercise in reducing proteinuria and glomerulosclerosis in spontaneously hypertensive rats.

Experimental studies in animal models have described the benefits of physical exercise (PE) to kidney diseases associated with hypertension. Land- and water-based exercises induce different responses in renal function. Our aim was to evaluate the renal alterations induced by different environments of PE in spontaneously hypertensive rats (SHRs). The SHRs were divided into sedentary (S), swimming exercise (SE), and running exercise (RE) groups, and were trained for 8 weeks under similar intensities (60 min/day). Arterial pressure (AP) and heart rate (HR) were recorded. The renal function was evaluated through urinary volume at each week of training; sodium and potassium excretions, plasma and urinary osmolarities, glomerular filtration rate (GFR), levels of proteinuria, and renal damage were determined. SE and RE rats presented reduced mean AP, systolic blood pressure, and HR in comparison with S group. SE and RE rats showed higher urine osmolarity compared with S. SE rats showed higher free water clearance (P < 0.01), lower urinary density (P < 0.0001), and increased weekly urine volume (P < 0.05) in comparison with RE and S groups. GFR was increased in both SE and RE rats. The proteinuria of SE (7.0 ± 0.8 mg/24 h) rats was decreased at the 8th week of the PE in comparison with RE (9.6 ± 0.8 mg/24 h) and S (9.8 ± 0.5 mg/24 h) groups. The glomerulosclerosis was reduced in SE rats (P < 0.02). SE produced different response in renal function in comparison with RE, in which only swimming-trained rats had better profile for proteinuria and glomerulosclerosis.

A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice.

Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (methyl donor-rich diet (MD) F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations. Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2, which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. Hippocampal overexpression of Kcnmb2 in MD F1 mice ameliorated altered spatial learning and memory, supporting a role of this BK channel subunit in the MD F1 behavioral phenotype. Behavioral and gene expression changes did not extend into the F2 offspring generation. Together, our data indicate that paternal dietary factors influence cognitive and neural functions in the offspring generation.

Factors associated with second-line triplet therapy in routine care in relapsed/refractory multiple myeloma.

WHAT IS KNOWN AND OBJECTIVE: Second-line therapy (SLT) trials in relapsed/refractory multiple myeloma (RRMM) report superior outcomes with triplet combinations. We sought to determine factors associated with triplet SLT in routine practice. METHODS: A retrospective cohort with claims for MM between 01/01/2008 and 03/31/2015 was grouped by 1-2 ("doublet") or 3+ ("triplet") agent therapy. Charlson comorbidity index (CCI) and disability status; CRAB symptoms (hypercalcaemia, renal/bone disease, anaemia); and relapse risk were determined. RESULTS: Among 623 patients, the triplet group (n=146 [23%]) was younger (65.2 vs 69.8 years) and more likely to have high-risk relapse (67% vs 50%), CRAB symptoms (94.5% vs 81.1%), triplet first-line treatment (75% vs 51%) and frontline stem cell transplant (38% vs 20%) (P<0.001 for all). In multivariate analyses, CRAB symptoms (OR: 3.22, 95% CI: 1.47, 7.10), high-risk relapse (OR: 1.71, 95% CI: 1.12, 2.62) and prior triplet therapy (OR: 2.16, 95% CI: 1.38, 3.40), but neither CCI nor disability, were associated with triplet SLT. A trend towards triplets among younger patients (<65 vs >75 years, OR: 1.73, 95% CI: 0.99, 3.04) was observed. WHAT IS NEW AND CONCLUSION: The majority of patients did not receive triplet regimens. Treatment selection with triplet therapy for RRMM should carefully consider comorbidities and patient-specific characteristics.

Investigating the familiarity effect in texture segmentation by means of event-related brain potentials.

The familiarity effect (FE) refers to the phenomenon that it is easier to find an unfamiliar element on a background of familiar elements than vice versa. In this study, we examined the FE in texture segmentation while recording event-related brain potentials with the aim to find out which processing stages were influenced by familiarity. In two experiments, with different levels of texture homogeneity, the N1, the N2p, and the P3 components were investigated. It was found that the FE in texture segmentation is associated with a modulation of the early N1 and of the intermediate N2p component for homogeneous textures. For inhomogeneous (jittered) textures, the FE was found for the intermediate N2p and for the late P3 components, but not for the N1 component. Our findings suggest that increasing texture inhomogeneity shifts the FE occurrence to later processing stages.

Tissue Expression of Aquaporin 2 Is Correlated to Urine Output and Allograft Function in Sensitized Kidney Transplant Patients.

BACKGROUND: Salt and water disturbances often occur during acute kidney allograft dysfunction that contribute to graft failure, but this condition has been poorly investigated in the alloreactivity setting. We evaluated the tissue expression of aquaporins (AQP1 and AQP2) and the epithelial sodium channel (ENAC) in kidney biopsy specimens from sensitized kidney transplant recipients. METHODS: Eighty-six biopsy specimens from 33 sensitized patients were divided into 3 groups according to clinical context: time-zero (n = 9), protocol (n = 9), and indication (n = 68). The indication biopsy specimens were further divided into 3 subgroups according to the presence of acute tubular necrosis or rejection. Normal kidney tissue samples (n = 6) served as the control specimens. Immmunohistochemical expression of AQP1, AQP2, and ENAC was determined by using image analyzing software. RESULTS: Significantly lower AQP1 expression was observed in the time-zero and indication biopsy specimens with rejection compared with control specimens (P = .03 and P = .04, respectively). AQP2 expression was significantly lower in patients with an indication biopsy specimen compared with control and protocol biopsy specimens (P = .05 and P = .005). For ENAC, a lower expression was noted in the indication biopsy specimens compared with the control specimens (P = .04). Both AQP1 and AQP2 tissue expressions were significantly correlated to urine output (r = 0.45 and r = 0.32; P = .001 and P = .02), and AQP2 was correlated with the glomerular filtration rate estimated by using the Modification of Diet in Renal Disease Study equation at biopsy (r = 0.23; P = .05). CONCLUSIONS: These findings partially confirm previous experimental data showing downregulation of AQP1 expression after ischemia/reperfusion injury and during rejection. AQP2 downregulation seems to be rejection-independent, occurring during deteriorating or poor kidney graft function.

Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.

Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR-GL (86 vs 0 vs 0%; log-rank P < 0.001) compared with post-transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant.

A Single-center Experience on the Value of Pancreas Graft Biopsies and HLA Antibody Monitoring After Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: In simultaneous pancreas-kidney transplantation (SPKT), monitoring of the pancreas allograft is more complex than the kidney allograft due to difficulties in obtaining pancreas histology and weak clinical evidence supporting the role of donor-specific antibodies (DSA). METHODS: We performed a single-center retrospective analysis of all 17 SPKT recipients who underwent a total of 22 pancreas allograft indication biopsies from October 2009 to September 2012. Fifteen patients had at least 2 DSA measurements: pretransplantation and at the time of biopsy. RESULTS: All 7 patients (100%) with post-transplantation DSA-positivity (de novo: n = 6; persistent: n = 1) at biopsy had at least 1 rejection episode either of the pancreas (n = 4) or the kidney (n = 3), with 3 antibody-mediated rejections (AMR). In contrast, only 4 of 8 patients (50%) without post-transplantation DSA had evidence of rejection, with 1 AMR. Findings during pancreas allograft biopsy procedures led to a change of immunosuppressive therapy in 11 of 15 (73%) patients. Patient survival, graft survival, and function were not adversely affected by the presence of post-transplantation DSA. One major and 2 minor procedure-related complications occurred during the pancreas biopsies. CONCLUSIONS: In this small retrospective analysis, pancreas allograft histology provided the most therapeutically relevant information, rather than the kidney histology or DSA monitoring.

[Development of an instrument for the assessment of demand and monitoring of the health management in a health insurance]. / Entwicklung eines Instruments zur Bedarfsermittlung und zum Monitoring im Betrieblichen Gesundheitsmanagement (BGM) eines Versicherungskonzerns.

To identify and follow up the health relevant effects of change-management-projects and to determine improvements in activities following this change a specific health-controlling instrument with benchmarking options has been developed. This instrument applies scientific quality standards and shows the organisational value in form of an index (BGM-Systemindex). It shows the correlation between the four indices management system, health-related actions, health and absence rate and allows a qualitative view of corporate health promotion on and its long term effects. The initiator for the project was an employee survey, which showed a need for action to improve job satisfaction. The survey was the reason that management initiated an integral change-management-project. The project showed many interfaces with the corporate health promotion (BGM), thus enabling consequent changes to be made and their effects to be evaluated. The aim of the project was to clearly increase employee satisfaction up to the next employee survey. Overall the project can be considered a success as the main aim of the project to increase the employees job satisfaction in the given period of time was clearly accomplished. The BGM-Systemindex also stood the test for comprehensive monitoring of the employees health. The project was able to prove that the health relevant parameters could be optimised and that the quality, acceptance and efficiency of the intervention methods had improved. It also showed a positive development of the early and long term health indicators. This is a positive contrast to available literature, which shows that an insufficient or incorrectly used change management results in a lower employee satisfaction. As a result it was decided to use the tool in future.