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Unlabelled: Dual energy X-ray absorptiometry of the whole body and the lumbar spine was performed to study bone mineralisation before and after 1 year of recombinant human growth hormone (rhGH) treatment in ten children with chronic renal failure. At the start, median age was 7.3 years (range 2.0-8.8 years) and median glomerular filtration rate 15 ml/min per 1.73 m2 (range 7-41 ml/min per 1.73 m2). Total body mineral content (TBMC), lumbar spine mineral content (LBMC), total body bone mineral density (TBMD) and lumbar spine mineral density (LBMD) improved significantly (P < 0.05) after 1 year of treatment. Bone mineral data before and after treatment were compared with two groups of controls, i.e. ten healthy children matched for age and ten healthy children matched for height. Patients' TBMC, LBMC, TBMD and LBMD data before treatment were no different from those of height-matched controls; the same was true after 1 year of treatment except for the patients' significantly better LBMD (P < 0.05). When compared with age-matched controls, patients had significantly lower baseline TBMC and LBMC levels before treatment; after treatment LBMC was no longer different. However, there were no differences in TBMD or LBMD between patients and age-matched controls at baseline or after rhGH.Conclusion: Recombinant human growth hormone treatment for 1 year results in a significant increase in both growth velocity and bone mineralisation. Comparison with height-matched controls shows a similar bone mineralisation at baseline and a better bone mineral density after treatment. [ABSTRACT FROM AUTHOR]

An abstract of the article "Transesophageal echocardiographic characterization of aortic valve morphology in patients with eccentric aortic regurgitation jets: Comparison with direct surgical inspection," by A. Pouleur and colleagues is presented.

An abstract of the article "Functional assessment of the mechanisms of aortic regurgitation by transesophageal echocardiography: Diagnostic accuracy and prediction of surgical repairability," by A. C. Pouleur and colleagues is presented.

Vernalisation-responsive plants use cold as a cue to monitor the passing of winter. Winter cereals can remember how much cold they have experienced, even when winter is punctuated by warm days. However, in a seemingly unnatural process called 'devernalisation', hot temperatures can erase winter memory. Previous studies in bread wheat (Triticum aestivum) have implicated the MADS-box transcription factor VEGETATIVE TO REPRODUCTIVE TRANSITION 2 (VRT2) in vernalisation based on transcriptional behaviour and ectopic expression. Here, we characterised three BdVRT2 loss-of-function alleles in the temperate model grass Brachypodium distachyon. In addition to extended vernalisation requirements, mutants showed delayed flowering relative to wild-type plants when exposed only briefly to warm temperatures after partial vernalisation, with flowering being unaffected when vernalisation was saturating. Together, these data suggest a role for BdVRT2 in both vernalisation and in its re-initiation when interrupted by warm temperatures. In controlled constant conditions, BdVRT2 transcription was not strongly affected by vernalisation or devernalisation. Yet, by monitoring BdVRT2 expression in seasonally varying and fluctuating conditions in an unheated greenhouse, we observed strong upregulation, suggesting that its transcription is regulated by fluctuating vernalising-devernalising conditions. Our data suggest that devernalisation by hot temperatures is not a peculiarity of domesticated cereal crops but is the extreme of the reversibility of vernalisation by warm temperatures and has broader biological relevance across temperate grasses., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

To promote improved trial design in upcoming randomized clinical trials in childhood chronic kidney disease (CKD), insight in the within- and inter-patient variability of uremic toxins with its nutritional, treatment- and patient-related confounding factors is of utmost importance. In this study, the within- and inter-patient variability of a selection of uremic toxins in a longitudinal cohort of children diagnosed with CKD was assessed, using the intraclass correlation coefficient (ICC) and the within-patient coefficient of variation (CV). Subsequently, the contribution of anthropometry, estimated glomerular filtration rate (eGFR), dietary fiber and protein, and use of (prophylactic) antibiotics to uremic toxin variability was evaluated. Based on 403 observations from 62 children (median seven visits per patient; 9.4 ± 5.3 years; 68% males; eGFR 38.5 [23.1; 64.0] mL/min/1.73 m 2 ) collected over a maximum of 2 years, we found that the within-patient variability is high for especially protein-bound uremic toxins (PBUTs) (ICC < 0.7; within-patient CV 37-67%). Moreover, eGFR was identified as a predominant contributor to the within- and inter-patient variability for the majority of solutes, while the impact of the child's anthropometry, fiber and protein intake, and antibiotics on the variability of uremic toxin concentrations was limited. Based on these findings, we would recommend future intervention studies that attempt to decrease uremic toxin levels to select a (non-dialysis) CKD study population with a narrow eGFR range. As the expected effect of the selected intervention should exceed the inter-patient variability of the selected uremic toxins, a narrow eGFR range might aid in improving the trial design.

Purpose: Apnea duration is dependent on three factors: oxygen storage, oxygen consumption, hypoxia and hypercapnia tolerance. While current literature focuses on maximal apneas to improve apnea duration, apnea trained individuals use timed-repeated submaximal apneas, called "O 2 and CO 2 tables". These tables claim to accommodate the body to cope with hypoxia and hypercapnia, respectively. The aim of this study was twofold. First, to investigate the determinants of maximal apnea duration in apnea novices. Second, to compare physiologic responses to maximal apneas, O 2 and CO 2 tables., Methods: After medical screening, lung function test and hemoglobin mass measurement, twenty-eight apnea novices performed three apnea protocols in random order: maximal apneas, O 2 table and CO 2 table. During apnea, peripheral oxygen saturation (SpO 2 ), heart rate (HR), muscle (mTOI) and cerebral (cTOI) tissue oxygenation index were measured continuously. End-tidal carbon dioxide (EtCO 2 ) was measured before and after apneas., Results: Larger lung volumes, higher resting cTOI and lower resting EtCO 2 levels correlated with longer apnea durations. Maximal apneas induced greater decreases in SpO 2 (- 16%) and cTOI (- 13%) than O 2 (- 8%; - 8%) and CO 2 tables (- 6%; - 6%), whereas changes in EtCO 2 , HR and mTOI did not differ between protocols., Conclusion: These results suggest that, in apnea novices, O 2 and CO 2 tables did not induce a more profound hypoxia and hypercapnia, but a similar reduction in oxygen consumption than maximal apneas. Therefore, apnea novices should mainly focus on maximal apneas to improve hypoxia and hypercapnia tolerance. The use of specific lung training protocols can help to increase oxygen storage capacity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Growth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central to the pathophysiology of growth failure is the presence of a chronic proinflammatory state, presumed to be partly driven by the accumulation of uremic toxins. In this study, we assessed the association between uremic toxin concentrations and height velocity in a longitudinal multicentric prospective pediatric CKD cohort of (pre)school-aged children and children during pubertal stages., Methods: In a prospective, multicentric observational study, a selection of uremic toxin levels of children (aged 0-18 years) with CKD stage 1 to 5D was assessed every 3 months (maximum 2 years) along with clinical growth parameters. Linear mixed models with a random slope for age and a random intercept for child were fitted for height (in cm and SD scores [SDS]). A piecewise linear association between age and height was assumed., Results: Data analysis included data from 560 visits of 81 children (median age 9.4 years; 2/3 male). In (pre)school aged children (aged 2-12 years), a 10% increase in concurrent indoxyl sulfate (IxS, total) concentration resulted in an estimated mean height velocity decrease of 0.002 SDS/yr ( P  < 0.05), given that CKD stage, growth hormone (GH), bicarbonate concentration, and dietary protein intake were held constant. No significant association with height velocity was found in children during pubertal stages (aged >12 years)., Conclusion: The present study demonstrated that, especially IxS contributes to a lower height velocity in (pre)school children, whereas we could not find a role for uremic toxins with height velocity during pubertal stages., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Objective: Current guidelines advise using prophylactic tricuspid valve annuloplasty during mitral valve surgery, especially in the presence of annular diameter enlargement. However, several retrospective studies and a prospective randomized study from our department could not confirm that diameter enlargement is predictive of late regurgitation. We examined whether 2- and 3-dimensional echocardiographic and clinical characteristics could identify patients who will develop moderate or severe recurrent tricuspid regurgitation., Methods: Patients with less than severe functional tricuspid regurgitation (FTR) were randomized not to receive tricuspid annuloplasty, and 11 of 53 of them were excluded from the study because 3-dimensional echocardiographic analysis was not possible. Cox regression was used to estimate the model-based probability of moderate or severe FTR (vena contracta ≥3 mm) or progression of TR and FTR regression using valve dimensions (annulus area, diameter perimeter, nonplanar angle, and sphericity index), dynamics (annulus contraction, annulus displacement, and displacement velocity), and clinical parameters as possible predictors., Results: At a median follow-up of 3.8 years (range, 3-5.6 years), 17 patients had moderate or severe FTR or progression, and 13 had FTR regression. Our models identified annular displacement velocity as a significant predictor for FTR recurrence and nonplanar angle as a significant predictor for FTR regression., Conclusions: Annular dynamics, not the dimension, predict recurrence and regression of FTR. Annular contraction should be systematically investigated as a possible surrogate of right ventricle function to prophylactically treat the tricuspid valve., (© 2023 The Author(s).)

Background: Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies., Methods: Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN)., Results: A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting., Conclusions: Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting., (© The Author(s) 2022. Published by Oxford University Press on behalf of ERA.)

Synaptic dysfunction is a hallmark of various neurodegenerative and neurodevelopmental disorders. To interrogate synapse function in a systematic manner, we have established an automated high-throughput imaging pipeline based on fluorescence microscopy acquisition and image analysis of electrically stimulated synaptic transmission in neuronal cultures. Identification and measurement of synaptic signal fluctuations is achieved by means of an image analysis algorithm based on singular value decomposition. By exploiting the synchronicity of the evoked responses, the algorithm allows disentangling distinct temporally correlated patterns of firing synapse populations or cell types that are present in the same recording. We demonstrate the performance of the analysis with a pilot compound screen and show that the multiparametric readout allows classifying treatments by their spatiotemporal fingerprint. The image analysis and visualization software has been made publicly available on Github ( https://www.github.com/S3Toolbox ). The streamlined automation of multi-well image acquisition, electrical stimulation, analysis, and meta-data warehousing facilitates large-scale synapse-oriented screens and, in doing so, it will accelerate the drug discovery process., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To compare long-term outcomes after bicuspid aortic valve (BAV) repair utilizing the Cabrol annuloplasty versus valve sparing Reimplantation technique., Methods: From 1996 to 2018, 340 consecutive patients underwent BAV repair. Eighty underwent Cabrol annuloplasty and 189 underwent Reimplantation. Exclusion criteria were re-repairs (n = 6), active endocarditis (n = 4), no annuloplasty (n = 41) and ring or suture annuloplasty (n = 20). We compared both groups for survival, reoperations, valve related events and recurrent severe aortic regurgitation (AR > 2+). Inverse probability weighting (IPW) was used to balance the 2 groups. Cox regression analysis was used to identify outcome predictors., Results: After weighting, pre- and intraoperative characteristics were similar between groups, except for aorta replacement techniques and operative time, which was longer in the Reimplantation group (P < 0.001). At 12 years, overall survival was similar between groups (IPW: Cabrol 97 ± 2% vs Reimplantation 94 ± 3%, P = 0.52). Freedom from reoperation and freedom from AR > 2+ were significantly lower in the Cabrol group (reoperation IPW: 69 ± 9% vs 91 ± 4%, P = 0.004 and AR > 2+ IPW: 71 ± 8% vs 97 ± 2%, P < 0.001). The Reimplantation technique was the only independent predictor of reoperation (hazard ratio 0.31; confidence interval 0.19-0.7; P = 0.005)., Conclusions: In this study, comparing 2 annuloplasty strategies for BAV repair, we found statistically significant differences in long-term durability favouring the Reimplantation technique, and no differences in overall survival. The results support our current strategy of Reimplantation technique and repair of AR in patients with BAV. Cabrol annuloplasty is obsolete and should be generally abandoned in patients undergoing BAV repair for AR., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Chronic kidney disease (CKD) in children is a pro-inflammatory condition leading to a high morbidity and mortality. Accumulation of organic metabolic waste products, coined as uraemic toxins, parallels kidney function decline. Several of these uraemic toxins are protein-bound (PBUT) and gut-derived. Gut dysbiosis is a hallmark of CKD, resulting in a state of increased proteolytic fermentation that might be counteracted by dietary fibre. Data on fibre intake in children with CKD are lacking. We aimed to assess dietary fibre intake in a paediatric CKD cohort and define its relationship with PBUT concentrations., Methods: In this multi-centre, cross-sectional observational study, 61 non-dialysis CKD patients (9 ± 5 years) were included. Dietary fibre intake was assessed through the use of 24-h recalls or 3-day food records and coupled to total and free levels of 4 PBUTs (indoxyl sulfate (IxS), p-cresyl sulfate (pCS), p-cresyl glucuronide (pCG) and indole acetic acid (IAA)., Results: In general, fibre intake was low, especially in advanced CKD: 10 ± 6 g/day/BSA in CKD 4-5 versus 14 ± 7 in CKD 1-3 (p = 0.017). Lower concentrations of both total (p = 0.036) and free (p = 0.036) pCG were observed in the group with highest fibre intake, independent of kidney function., Conclusions: Fibre intake in paediatric CKD is low and is even worse in advanced CKD stages. Current dietary fibre recommendations for healthy children are not being achieved. Dietary management of CKD is complex in which too restrictive diets carry the risk of nutritional deficiencies. The relation of fibre intake with PBUTs remains unclear and needs further investigation. Graphical abstract.

Purpose: Hardikar syndrome (MIM 612726) is a rare multiple congenital anomaly syndrome characterized by facial clefting, pigmentary retinopathy, biliary anomalies, and intestinal malrotation, but with preserved cognition. Only four patients have been reported previously, and none had a molecular diagnosis. Our objective was to identify the genetic basis of Hardikar syndrome (HS) and expand the phenotypic spectrum of this disorder., Methods: We performed exome sequencing on two previously reported and five unpublished female patients with a clinical diagnosis of HS. X-chromosome inactivation (XCI) studies were also performed., Results: We report clinical features of HS with previously undescribed phenotypes, including a fatal unprovoked intracranial hemorrhage at age 21. We additionally report the discovery of de novo pathogenic nonsense and frameshift variants in MED12 in these seven individuals and evidence of extremely skewed XCI in all patients with informative testing., Conclusion: Pathogenic missense variants in the X-chromosome gene MED12 have previously been associated with Opitz-Kaveggia syndrome, Lujan syndrome, Ohdo syndrome, and nonsyndromic intellectual disability, primarily in males. We propose a fifth, female-specific phenotype for MED12, and suggest that nonsense and frameshift loss-of-function MED12 variants in females cause HS. This expands the MED12-associated phenotype in females beyond intellectual disability.

Imbalanced colonic microbial metabolism plays a pivotal role in generating protein-bound uraemic toxins (PBUTs), which accumulate with deteriorating kidney function and contribute to the uraemic burden of children with chronic kidney disease (CKD). Dietary choices impact the gut microbiome and metabolism. The aim of this study was to investigate the relation between dietary fibre and gut-derived PBUTs in paediatric CKD. Sixty-one (44 male) CKD children (9 ± 5 years) were prospectively followed for two years. Dietary fibre intake was evaluated by either 24-h recalls (73%) or 3-day food records (27%) at the same time of blood sampling for assessment of total and free serum levels of different PBUTs using liquid chromatography. We used linear mixed models to assess associations between fibre intake and PBUT levels. We found an inverse association between increase in fibre consumption (g/day) and serum concentrations of free indoxyl sulfate (-3.1% (-5.9%; -0.3%) ( p = 0.035)), free p-cresyl sulfate (-2.5% (-4.7%; -0.3%) ( p = 0.034)), total indole acetic acid (IAA) (-1.6% (-3.0%; -0.3%) ( p = 0.020)), free IAA (-6.6% (-9.3%; -3.7%) ( p < 0.001)), total serum p-cresyl glucuronide (pCG) (-3.0% (-5.6%; -0.5%) ( p = 0.021)) and free pCG levels (-3.3% (-5.8%; -0.8%) ( p = 0.010)). The observed associations between dietary fibre intake and the investigated PBUTs highlight potential benefits of fibre intake for the paediatric CKD population. The present observational findings should inform and guide adaptations of dietary prescriptions in children with CKD.

Background: Postoperative delirium (POD) is a frequent complication in older patients. Dexmedetomidine might be effective in decreasing the incidence of POD. We hypothesised that adding low-dose rate dexmedetomidine infusion to a propofol sedation regimen would have fewer side-effects and would counteract the possible delirium producing properties of propofol, resulting in a lower risk of POD than propofol with placebo., Methods: In this double-blind placebo-controlled trial, patients ≥60 yr old undergoing on-pump cardiac surgery were randomised 1:1 to the following postoperative sedative regimens: a propofol infusion and dexmedetomidine (0.4 μg kg -1 h -1 ) or a propofol infusion and saline 0.9% (placebo group). The study drug was started at chest closure and continued for 10 h. The primary endpoint was in-hospital POD, assessed using the Confusion Assessment Method and chart review method., Results: POD over the course of hospital stay occurred in 31/177 (18%) and 33/172 (19%) patients in the dexmedetomidine and placebo arm, respectively (P=0.687; odds ratio=0.89; 95% confidence interval, 0.52-1.54). The incidence of POD in the intensive care alone, or on the ward alone, was also not significantly different between the groups. Subjects in the dexmedetomidine group spent less median time in a delirious state (P=0.026). Median administered postoperative norepinephrine was significantly higher in the dexmedetomidine group (P<0.001). One patient in the dexmedetomidine group and 10 patients in the placebo group died in the hospital., Conclusions: Adding low-dose rate dexmedetomidine to a sedative regimen based on propofol did not result in a different risk of in-hospital delirium in older patients undergoing cardiac surgery. With a suggestion of both harm and benefit in secondary outcomes, supplementing postoperative propofol with dexmedetomidine cannot be recommended based on this study., Clinical Trial Registration: NCT03388541., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Nephropathic cystinosis, a hereditary lysosomal storage disorder caused by dysfunction of the lysosomal cotransporter cystinosin, leads to cystine accumulation and cellular damage in various organs, particularly in the kidney. Close therapeutic monitoring of cysteamine, the only available disease-modifying treatment, is recommended. White blood cell cystine concentration is the current gold standard for therapeutic monitoring, but the assay is technically demanding and is available only on a limited basis. Because macrophage-mediated inflammation plays an important role in the pathogenesis of cystinosis, biomarkers of macrophage activation could have potential for the therapeutic monitoring of cystinosis., Methods: We conducted a 2-year prospective, longitudinal study in which 61 patients with cystinosis who were receiving cysteamine therapy were recruited from three European reference centers. Each regular care visit included measuring four biomarkers of macrophage activation: IL-1 β , IL-6, IL-18, and chitotriosidase enzyme activity., Results: A multivariate linear regression analysis of the longitudinal data for 57 analyzable patients found chitotriosidase enzyme activity and IL-6 to be significant independent predictors for white blood cell cystine levels in patients of all ages with cystinosis; a receiver operating characteristic analysis ranked chitotriosidase as superior to IL-6 in distinguishing good from poor therapeutic control (on the basis of white blood cell cystine levels of <2 nmol 1/2 cystine/mg protein or ≥2 nmol 1/2 cystine/mg protein, respectively). Moreover, in patients with at least one extrarenal complication, chitotriosidase significantly correlated with the number of extrarenal complications and was superior to white blood cell cystine levels in predicting the presence of multiple extrarenal complications., Conclusions: Chitotriosidase enzyme activity holds promise as a biomarker for use in therapeutic monitoring of nephropathic cystinosis., (Copyright © 2020 by the American Society of Nephrology.)

Four biomarkers are commonly employed to diagnose B12 deficiency: vitamin B12 (B12), holotranscobalamin (HoloTC), methylmalonic acid (MMA), and homocysteine (Hcy). 4cB12, a combined index of the B12 status, has been suggested to improve the recognition of B12 deficiency. We aimed to evaluate the four different markers for detecting B12 deficiency, as determined by 4cB12. Within a large, mixed patient population, 11,833 samples had concurrent measurements of B12, HoloTC, MMA, and Hcy. 4cB12 was calculated according to the methods described by Fedosov. Diagnostic cutoffs as well as diagnostic accuracy for the detection of B12 deficiency were assessed with receiver operating characteristic (ROC) analysis. The median age was 56 years, and women accounted for 58.8% of the samples. Overall, the area under the curve (AUC) for the detection of subclinical B12 deficiency was highest for HoloTC (0.92), followed by MMA (0.91), B12 (0.9) and Hcy (0.78). The difference between HoloTC and B12 was driven by a significantly higher AUC for HoloTC (0.93) than for B12 (0.89), MMA (0.91), and Hcy in women 50 years and older (0.79; p < 0.05 for all). In the detection of subclinical B12 deficiency, there were no significant differences in the AUCs of HoloTC, B12, and MMA among men and women <50 years. In conclusion, in women < 50 years and in men, HoloTC, MMA, or Hcy do not appear superior to B12 for the detection of B12 deficiency. For women 50 years and older, HoloTC seems to be the preferred first-line marker for the detection of subclinical B12 deficiency., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Araceli Jarquin Campos et al.)

Background: Improved management of growth impairment might have resulted in less growth retardation after pediatric kidney transplantation (KT) over time. We aimed to analyze recent longitudinal growth data after KT in comparison to previous eras, its determinants, and the association with transplant outcome in a large cohort of transplanted children using data from the European Society for Paediatric Nephrology/European Renal Association and European Dialysis and Transplant Association Registry., Methods: A total of 3492 patients transplanted before 18 years from 1990 to 2012 were included. Height SD scores (SDS) were calculated using recent national or European growth charts. We used generalized equation models to estimate the prevalence of growth deficit and linear mixed models to calculate adjusted mean height SDS., Results: Mean adjusted height post-KT was -1.77 SDS. Height SDS was within normal range in 55%, whereas 28% showed moderate, and 17% severe growth deficit. Girls were significantly shorter than boys, but catch-up growth by 5 years post-KT was observed in both boys and girls. Children <6 years were shortest at KT and showed the greatest increase in height, whereas there was no catch-up growth in children transplanted >12., Conclusions: Catch-up growth post-KT remains limited, height SDS did not improve over time, resulting in short stature in nearly half of transplanted children in Europe.

Objectives: Our goal was to assess the aortic leaflet free margin length (FML) and geometric height (gH) in a normal aortic valve (AV), aorta dilatation and aortic leaflet prolapse., Methods: We measured the FML and gH intraoperatively in 132 patients operated on for aortic insufficiency, aortic dilatation, endocarditis or fibroelastoma. Patients were divided into 3 groups: normal tricuspid AV (group 1, n = 12), aortic dilatation (group 2, tricuspid = 43, bicuspid = 18) and leaflet prolapse (group 3, tricuspid = 32, bicuspid = 27). The FML and gH were compared between the groups and between the leaflets within each group., Results: In a normal tricuspid AV, the mean FML and gH were 34.7 ± 3.1 mm and 18.8 ± 1.7 mm, respectively. In group 2 tricuspid, the FML and gH were greater than those in group 1 (FML 43.7 ± 4.4, P < 0.001; gH 21.2 ± 1.8, P = 0.003). In group 3, tricuspid, the FML of the prolapsing leaflet was greater than the FML of the non-prolapsing leaflet (48.3 ± 5.4 vs 42.2 ± 3.6; P < 0.001). In group 2, bicuspid, FML of both leaflets were similar in group 2, but augmented on the fused leaflet compared to the non-fused leaflet in group 3 (fused 55.4 ± 6.3; non-fused 46.2 ± 6.2; P < 0.001). In groups 2 and 3 bicuspid, the gH of the non-fused leaflet was systematically greater than the fused leaflet (group 2 non-fused 24.6 ± 2.5 vs fused 20.4 ± 2.1; P < 0.001)., Conclusions: In aortic dilatation and leaflet prolapse, FML and, to a lesser extent, gH increased significantly compared to those of normal AV function. FML and gH dimensions also depended on the valve configuration (tricuspid/bicuspid). These data provide new insight into the pathomorphology of AV disease and will serve to further develop new methods of AV repair based on intraoperative measurements of the FML., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Studies have associated electroencephalogram (EEG) suppression with postoperative delirium (POD) and postoperative cognitive decline (POCD). Otherwise, improving cerebral tissue oxygen saturation (rScO 2 ) seems beneficial. No study has evaluated the impact of EEG suppression and decreased rScO 2 on the incidence of POD and POCD when the intraoperative management of patients is performed with a depth-of-anesthesia (DOA) monitor and a cerebral oximetry. In this prospective study patients undergoing cardiac interventions were monitored with the NeuroSENSE ® DOA monitor and bilateral cerebral oximetry. An algorithm was used to optimize cerebral oxygenation. EEG suppression was presented as total area under the curve (AUC) of suppression ratio (SR) > 0 s (AUC EEGSR>0s ). Cerebral desaturation was defined as AUC of 25% drop of oximetry values as compared to baseline. POD was evaluated by the chart review method. POCD was defined as a Z-score ≤ 2 based on Mini Mental State Examination at baseline and day 5 or if the patient reported any cognitive decline at 3 and at 6 months postoperatively. Among the 1616 patients, 1513 underwent normothermic surgery and were further analyzed. POD and POCD were respectively evaluated in 1504 and 1350 patients of whom 303 (20%) and 270 (20%) were respectively diagnosed positive. Having experienced high magnitudes of EEG suppression (fourth quartile of AUC EEGSR>0s ) was significantly associated with POD (OR = 2.247; 95% CI = 1.414-3.571; P = 0.001). Low rScO 2 at the end of surgery was statistically associated with POCD (OR = 0.981; 95% CI = 0.965-0.997; P = 0.018). The results of our study show that the degree of intraoperative EEG suppression on one hand, and low rScO 2 at the end of procedure on the other hand, are associated with respectively POD and POCD in patients undergoing cardiac interventions.

Objective: Delta pulse pressure and delta down are used as dynamic preload indicators of fluid responsiveness during closed chest surgery. There are few data regarding their accuracy in open chest surgery. The present study aimed to evaluate the influence of sternotomy on the accuracy of both delta pulse pressure and delta down., Design: Prospective study., Setting: Single institution, nonacademic hospital., Participants: The study comprised 127 adult patients scheduled for elective open chest cardiac surgery., Interventions: Delta pulse pressure and delta down were calculated for all patients before and 10 minutes after sternotomy., Measurements and Main Results: Statistical analyses were performed to assess the influence of sternotomy on the accuracy of delta down and delta pulse pressure. Mann-Whitney and Bland-Altman analyses demonstrated a significant influence of sternotomy on delta pulse pressure values but not on delta down values. Among patients who had a positive delta down and/or delta pulse pressure before sternotomy, sternotomy significantly modified the delta pulse pressure value (p = 0.02), but not the delta down value (p = 0.22). The kappa coefficient indicated a very good agreement between delta down before and after sternotomy (0.83) and a fair agreement between delta pulse pressure before and after sternotomy (0.4). The difference between kappa coefficients was highly significant (p < 0.001)., Conclusions: Within the study population, sternotomy significantly influenced delta pulse pressure but not delta down. In this preliminary study, delta down appeared to be more accurate to evaluate fluid responsiveness during open chest surgery than did delta pulse pressure. Before promoting delta down in current practice, confirmation is needed on a larger scale., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort ( n = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4-5 ( n = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients ( r s ). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4-5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF ( r s -0.2 to -0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4-5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population.

Objectives:: The bicuspid aortic valve (BAV) exists in a wide variety of valve phenotypes. The aim of this study was to assess the anatomical characteristics of the different phenotypes and develop a classification system to aid surgical repair., Methods:: In 178 consecutive patients operated on for aortic insufficiency or aortic dilatation in 2 centres, 11 anatomical parameters of BAV were measured by echocardiography and intraoperatively. All BAV judged potentially repairable were included in the study., Results:: Commissural orientation correlated positively with fusion length (R2 = 0.6, P < 0.001) and negatively with non-functional commissure height (R2 = 0.45, P < 0.001). The cohort was divided into 3 groups according to their commissural orientation (type A: symmetrical, 160-180°, n = 73; type B: asymmetrical, 140-159°, n = 74; and type C: very asymmetrical, 120-139°, n = 31). The patterns of cusp fusion, annulus and aortic size were similar among the groups. Fusion length and the geometric height of the cusps decreased from type A to C; non-functional commissure height increased from type A to C (P < 0.05). Patient age increased from type A to type C. Isolated aortic dilatation was more frequent in type A, and severe aortic insufficiency was more frequent in types B and C (P < 0.05). Valve repair techniques and management of commissural orientation varied among the 3 groups (P < 0.05). Aortic valve replacement and residual aortic insufficiency after repair were more frequent in type C (P < 0.05)., Conclusions:: The BAV phenotypes follow a continuous spectrum that extends from symmetrical to very asymmetrical BAV. We describe the main anatomical parameters (including commissure orientation, length of fusion and non-functional commissure height) and their variation across this spectrum. We propose a new repair-oriented classification system based on those parameters that can be used to predict valve repair techniques. This classification needs further validation with regards to surgical techniques and long-term outcomes., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aim of Study: Person-centered medicine (PCM) with its focus on humanistic-biographical-oriented medicine and integrated, positive-salutogenic health is a central aspect in the patient-physician relationship in general practice. The objective of this analysis is to assess the prevalence and type of research project in academic institutions of general practice in Germany (Ger) and Austria (At) and the thematic priorities of the projects in the areas PCM, health promotion (HP), prevention (PRE) and conventional medicine (CM)., Methods: A search was conducted (September-December 2015) on the websites of 30 institutes and divisions of general medicine for their current research projects. The retrieved projects were assigned to five categories: PCM, HP, PRE, CM and others. Subsequently, we identified the targeted patient groups of the projects as well as the thematic focus in the categories PCM, HP, PRE and CM with focus on PCM and HP., Results: 541 research projects were identified, 452 in Germany and 89 in Austria. Research projects were only included if they were explicitly indicated as research-oriented. Seventy projects addressed PCM aspects, 15 projects HP aspects, 32 projects PRE aspects and 396 projects CM aspects. The most frequently target groups in the categories PCM (24 of 70) and HP (7 of 15) were chronically ill patients. The most common thematic focus in PCM was communication (13 of 70) and in HP, physical activity (6 of 15)., Conclusion: The vast majority of research projects investigated conventional medical topics. The percentage of research activities in the field of PCM (13%) or PCM including HP (16%) in Ger and At is below the European average of 20%. From our point of view, PCM and HP need to be implemented to a greater extent in general practice., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Studies evaluating the hemostatic effects of fibrinogen administration in cardiac surgery are not conclusive., Aims: We investigated whether the use of a low-dose human fibrinogen in case of clinical bleeding after protamine administration and concomitant low FIBTEM values is effective in reducing postoperative bleeding. Secondary end-point was to investigate the consumption of allogeneic blood products., Setting and Design: This was a retrospective matched study conducted at university hospital., Materials and Methods: Among 2257 patients undergoing surgery with cardiopulmonary (CPB) bypass, 73 patients received a median dose of 1 g human fibrinogen (ROTEM-Fibri group). This group was matched with 73 patients who had not received human fibrinogen (control group) among 390 patients having undergone surgery at the moment FIBTEM analysis was unavailable., Statistical Analysis: Matching was performed for the type and the presence of redo surgery. McNemar and Wilcoxon paired tests were used to respectively compare the categorical and quantitative variables., Results: The CPB bypass time was significantly higher in the ROTEM-Fibri group (P = 0.006). This group showed significantly higher bleeding in the first 12 and 24 h postoperatively (P < 0.001) and required significantly more transfusion of blood products (P < 0.001) and surgical revision (P = 0.007) when compared with the control group. There was no significant difference in the number of thromboembolic complications., Conclusions: These results show that the administration of 1 g of fibrinogen based on low-FIBTEM values and clinical bleeding after protamine administration does not stop bleeding and the need for transfusion of allogeneic blood products., Competing Interests: There are no conflicts of interest

Neurological disorders display a broad spectrum of clinical manifestations. Yet, at the cellular level, virtually all these diseases converge into a common phenotype of dysregulated synaptic connectivity. In dementia, synapse dysfunction precedes neurodegeneration and cognitive impairment by several years, making the synapse a crucial entry point for the development of diagnostic and therapeutic strategies. Whereas high-resolution imaging and biochemical fractionations yield detailed insight into the molecular composition of the synapse, standardized assays are required to quickly gauge synaptic connectivity across large populations of cells under a variety of experimental conditions. Such screening capabilities have now become widely accessible with the advent of high-throughput, high-content microscopy. In this review, we discuss how microscopy-based approaches can be used to extract quantitative information about synaptic connectivity in primary neurons with deep coverage. We elaborate on microscopic readouts that may serve as a proxy for morphofunctional connectivity and we critically analyze their merits and limitations. Finally, we allude to the potential of alternative culture paradigms and integrative approaches to enable comprehensive profiling of synaptic connectivity.