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Intraoperative neurophysiological information could increase accuracy of surgical deep brain stimulation (DBS) lead placement. Subsequently, DBS therapy could be optimized by specifically targeting pathological activity. In Parkinson’s disease, local field potentials (LFPs) excessively synchronized in the beta band (13–35 Hz) correlate with akinetic-rigid symptoms and their response to DBS therapy, particularly low beta band suppression (13–20 Hz) and high frequency gamma facilitation (35–250 Hz). In dystonia, LFPs abnormally synchronize in the theta/alpha (4–13 Hz), beta and gamma (60–90 Hz) bands. Phasic dystonic symptoms and their response to DBS correlate with changes in theta/alpha synchronization. In essential tremor, LFPs excessively synchronize in the theta/alpha and beta bands. Adaptive DBS systems will individualize pathological characteristics of neurophysiological signals to automatically deliver therapeutic DBS pulses of specific spatial and temporal parameters.

There has been a proliferation of studies demonstrating important sex differences in cognitive aging and dementia, and with this an increased interest in the role of menopause and sex steroid hormones in women's brain health. Foundational longitudinal studies of cognitive changes from the premenopause to perimenopause stage have shown reliable declines in verbal memory, with variable findings in processing speed, attention/working memory and verbal fluency. Continued research is needed to advance understanding of the range of cognitive domains affected, the duration of cognitive changes, the generalizability of these changes across cultures, the factors that account for such changes and the factors that can improve cognition at this time. In this article, we briefly review and draw on findings from large longitudinal studies of cognitive changes across the menopause transition to inform the design of future studies on this topic. We focus on key issues such as objective versus subjective cognitive measures; cognitive domains and tests; staging menopause; study design; mediators of cognitive effects (including hormones and menopause symptoms); and consideration of key covariates. We suggest that a more uniform and evidence-based approach to the investigation of these issues can advance the quality of the science in menopause and cognition.

Introduction Disease-causing mutations in the protocadherin FAT1 have been recently described both in patients with a glomerulotubular nephropathy and in patients with a syndromic nephropathy. Methods We identified 4 patients with FAT1-associated disease, performed clinical and genetic characterization, and compared our findings to the previously published patients. Patient-derived primary urinary epithelial cells were analyzed by quantitative polymerase chain reaction (qPCR) and immunoblotting to identify possible alterations in Hippo signaling. Results Here we expand the spectrum of FAT1-associated disease with the identification of novel FAT1 mutations in 4 patients from 3 families (homozygous truncating variants in 3, compound heterozygous missense variants in 1 patient). All patients show an ophthalmologic phenotype together with heterogeneous renal phenotypes ranging from normal renal function to early-onset end-stage kidney failure. Molecular analysis of primary urine-derived urinary renal epithelial cells revealed alterations in the Hippo signaling cascade with a decreased phosphorylation of both the core kinase MST and the downstream effector YAP. Consistently, we found a transcriptional upregulation of bona fide YAP target genes. Conclusion A comprehensive review of the here identified patients and those previously published indicates a highly diverse phenotype in patients with missense mutations but a more uniform and better recognizable phenotype in the patients with truncating mutations. Altered Hippo signaling and de-repressed YAP activity might be novel contributing factors to the pathomechanism in FAT1-associated renal disease., Graphical abstract

ZUSAMMENFASSUNGOft wird zur Behandlung eines kompliziert verlaufenden nephrotischen Syndroms des Kindesalters eine immunsuppressive Dauertherapie eingesetzt. Als first-line-Therapie beim kompliziert verlaufenden steroidsensiblen nephrotischen Syndrom hat sich in Deutschland in den letzten Jahren Mycophenlatmofetil etabliert. Muss aber ein Calcineurininhibitor eingesetzt werden, kann zwischen Ciclosporin A und Tacrolimus gewählt werden. In dieser Übersichtsarbeit werden die Vor- und Nachteile beider Therapien beleuchtet, die Indikationsstellung bei den unterschiedlichen Verlaufsformen des nephrotischen Syndroms erläutert und mögliche Entscheidungshilfen bei der Wahl des Calcineurininhibitors gegeben.

ZUSAMMENFASSUNGIn der Pädiatrie ist die Heimdialyse in Form von Peritonealdialyse seit Langem ein wesentlicher Bestandteil der Behandlung und wird bei der überwiegenden Anzahl, insbesondere bei sehr kleinen Kindern, eingesetzt. Trotz der Risiken, die eine Heimdialysebehandlung beinhaltet, überwiegen die Vorteile. Die Heimhämodialyse hingegen hat aktuell keinen großen Stellenwert in der Behandlung pädiatrischer Dialysepatienten, die Gründe hierfür sind vielfältig. Sie sollte aber in Zukunft mehr Berücksichtigung finden. Der vielfach bewiesene Vorteil der intensivierten Hämodialyse, die im Gegensatz zur Zentrumsdialyse als Heimdialyse logistisch einfacher durchzuführen ist, sollte dazu führen, in Zukunft die Heimdialyseverfahren durch einfacher zu bedienende, kleinere Geräte sowie unterstützende Systeme wie, z. B. Remote-controlled Patientenmanagement-Programme, weiter zu entwickeln.

In Germany, widespread full closures of schools and day care facilities were part of lockdown measures to control the spread of coronavirus disease 2019 (COVID-19). In the state of North Rhine-Westphalia closures took place on March 16, 2020 and were gradually eased from end of April 2020 until beginning of June 2020.This study aims to evaluate the prevalence of COVID-19 among children and adolescents during the reopening period of schools and day care facilities in Cologne, North Rhine-Westphalia, Germany. It further depicts medical history and results of physical examinations of pediatric patients undergoing a test for severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2).Testing for SARS-CoV-2 was carried out by a naso- and / or oropharyngeal swab by local pediatricians at the time of presentation. Samples were analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). Medical history and physical examination results were retrospectively analyzed.525 children and adolescents presented mainly with mild upper respiratory tract infections. Three patients were diagnosed with COVID-19. Their medical history and examination results did not stand out from the other patients.A precautious stepwise opening of schools and day care facilities was not associated with the occurrence of a relevant prevalence of COVID-19 among children and adolescents. However, a low general prevalence of COVID-19 at the end of the observation period has to be taken into account. Systematic testing might enable adjusted regulations in favor of full closures, especially in the light of increasing evidence for pediatric patients constituting a low-risk group for COVID-19.In Deutschland zählt die Schließung von Schulen und Kindertagesstätten zu den Maßnahmen, welche die Ausbreitung von Coronavirus disease 2019 (COVID-19) begrenzen sollen. In Nordrhein-Westfalen fanden die ersten Schließungen am 16. März 2020 statt und wurden von Ende April bis Anfang Juni 2020 schrittweise gelockert. ZIEL: Diese Studie soll einen Einblick in die Prävalenz von COVID-19 bei Kindern und Jugendlichen während der Wiedereröffnungsphase der Schulen und Kindertagesstätten in Köln, Nordrhein-Westfalen, geben. Weiterhin sollen die Anamnese und die Ergebnisse klinischer Untersuchungen der Patienten erfasst werden, bei denen ein Test auf das severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) vorgenommen wird.Die Testung auf SARS-CoV-2 wurde durch einen naso- und / oder oropharyngealen Abstrich durch niedergelassene Kinderärzte vorgenommen. Die Proben wurden mittels real-time reverse transcription polymerase chain reaction (RT-PCR) analysiert. Die Anamnese und die Ergebnisse der körperlichen Untersuchungen wurden retrospektiv ausgewertet. Ergebnis Es wurden 525 Kinder und Jugendliche mit vorwiegend milden Infektionen der oberen Atemwege eingeschlossen. Bei drei Patienten wurde COVID-19 diagnostiziert. Ihre Anamnese und die Ergebnisse der körperlichen Untersuchung unterschied sich nicht merklich von den anderen Patienten. Eine vorsichtige und schrittweise Wiedereröffnung der Schulen und Kindertagesstätten war nicht mit einer relevanten Prävalenz von COVID-19 bei Kindern- und Jugendlichen vergesellschaftet. Allerdings muss berücksichtigt werden, dass zum Zeitpunkt der Untersuchung eine niedrige Gesamtprävelanz in der Bevölkerung vorlag. Eine systematische Testung in Schulen und Kindertagesstätten und spezifische Regulationsmaßnahmen erscheinen gegenüber Vollschließungen vorteilhaft. Dies insbesondere in Anbetracht des niedrigen Risikos für Kinder- und Jugendliche, an COVID-19 schwer zu erkranken.

BACKGROUND: Pharmacokinetic monitoring is insufficient to estimate the intensity of immunosuppression after transplantation. Virus-specific T cells correlate with both virus-specific and general cellular immune defense. Additional steering of immunosuppressive therapy by virus-specific T cell levels might optimize dosing of immunosuppressants. METHODS: In a multicenter, randomized, controlled trial, we randomized 64 pediatric kidney recipients to a control group with trough-level monitoring of immunosuppressants or to an intervention group with additional steering of immunosuppressive therapy by levels of virus-specific T cells (quantified by cytokine flow cytometry). Both groups received immunosuppression with cyclosporin A and everolimus in the same target range of trough levels. Primary end point was eGFR 2 years after transplantation. RESULTS: In the primary analysis, we detected no difference in eGFR for the intervention and control groups 2 years after transplantation, although baseline eGFR 1 month after transplantation was lower in the intervention group versus the control group. Compared with controls, patients in the intervention group received significantly lower daily doses of everolimus and nonsignificantly lower doses of cyclosporin A, resulting in significantly lower trough levels of everolimus (3.5 versus 4.5 µg/L, P

Coronaviruses infect many animals, including humans, due to interspecies transmission. Three of the known human coronaviruses: MERS, SARS-CoV-1, and SARS-CoV-2, the pathogen for the COVID-19 pandemic, cause severe disease. Improved methods to predict host specificity of coronaviruses will be valuable for identifying and controlling future outbreaks. The coronavirus S protein plays a key role in host specificity by attaching the virus to receptors on the cell membrane. We analyzed 1238 spike sequences for their host specificity. Spike sequences readily segregate in t-SNE embeddings into clusters of similar hosts and/or virus species. Machine learning with SVM, Logistic Regression, Decision Tree, Random Forest gave high average accuracies, F1 scores, sensitivities and specificities of 0.95–0.99. Importantly, sites identified by Decision Tree correspond to protein regions with known biological importance. These results demonstrate that spike sequences alone can be used to predict host specificity., Highlights • Coronavirus spike protein sequences can predict host specificity. • Machine learning had accuracies of >0.98 for classification of human vs non-human hosts. • Decision Tree classifier identified spike regions with important biological roles . • Clustering with t-SNE embeddings correctly segregated sequences by virus genus and host .

In Deutschland sind aktuell (Stand 18.06.2020) 187.764 SARS-CoV-2-Infektionen gemeldet. 6,9 % der Infizierten sind dabei unter 19 Jahre. Es gibt erste Hinweise darauf, dass Kinder haufig asymptomatisch sind und einen milderen Verlauf zeigen. Ziel dieser Arbeit war es, eine Aussage bezuglich der Infektionspravalenz in dieser speziellen Patientengruppe zu ermoglichen. Im Rahmen der SARS-CoV-2-Pandemie wurden zwischen dem 13.03.2020 und dem 18.06.2020 alle Kinder und Jugendlichen, welche entweder zum Ausschluss einer SARS-CoV-2-Infektion oder als Verdachtsfall einen Abstrich auf SARS-CoV‑2 erhielten, erfasst. Die Daten wurden auf standardisierten Anamnesebogen gesammelt und retrospektiv anonymisiert ausgewertet. In dem Zeitraum wurden 2192 Kinder und Jugendliche auf SARS-CoV‑2 abgestrichen. 37 Patienten wurden positiv getestet (1,7 %). 36/37 waren Verdachtsfalle, und 28/37 waren symptomatisch. Fuhrende Symptome waren trockener Husten, Schnupfen und Fieber. Drei Kinder mussten stationar betreut werden. Keines zeigte einen schweren Verlauf. Unter den Getesteten waren 505 Patienten, die aufgrund ihrer chronischen Grunderkrankung als Risikopatienten eingestuft wurden, von denen 3 (0,6 %) einen positiven Nachweis mit asymptomatischem bzw. mildem Verlauf hatten. Hiermit konnen die ersten Daten bestatigt werden, wonach Kinder und Jugendliche haufig asymptomatische oder klinisch milde Infektions- bzw. Erkrankungsverlaufe zeigen. Zudem fanden wir keinen Hinweis fur eine hohe Dunkelziffer fur SARS-CoV-2-Infektionen in dieser regionalen padiatrischen Kohorte.

ZUSAMMENFASSUNGDas therapeutische Drug-Monitoring (TDM) einer immunsuppressiven Therapie kann einen wichtigen Beitrag zur klinischen Einschätzung des Verlaufes und zur Effektivität der Behandlung leisten. Ziel des TDMs sollte die Optimierung der Medikamentendosierung sein, um eine gute Effektivität bei minimaler Toxizität zu erreichen. Ein TDM kann pharmakokinetisch, pharmakodynamisch und pharmakogenetisch erfolgen. Näher wird auf die Besonderheiten des TDMs von Mycophenolatmofetil (MMF) und Tacrolimus eingegangen. Des Weiteren werden Grundprinzipien und Einflussfaktoren eines TDMs erläutert.

C3 glomerulonephritis (C3GN) is a rare but severe form of kidney disease caused by fluid-phase dysregulation of the alternative complement pathway. Causative mutations in complement regulating genes as well as auto-immune forms of C3GN have been described. However, therapy and prognosis in individual patients remain a matter of debate and long-term data are scarce. This also applies for the management of transplant patients as disease recurrence post-transplant is frequent. Here, we depict the clinical courses of two sisters with the unique combination of an identical, homozygous mutation in the complement factor H (CFH) gene as well as autoantibodies with a clinical follow-up of more than 20 years. Interestingly, the sisters presented with discordant clinical courses of C3GN with normal kidney function in one (patient A) and end-stage kidney disease in the other sister (patient B). In patient B, eculizumab was administered immediately prior to and in the course after kidney transplantation, with the result of a stable graft function without any signs of disease recurrence. Comprehensive genetic work-up revealed no further disease-causing mutation in both sisters. Intriguingly, the auto-antibody profile substantially differed in both sisters: autoantibodies in patient A reduced the C3b deposition, while the antibodies identified in patient B increased complement activation and deposition of split products. This study underlines the concept of a personalized-medicine approach in complement-associated diseases after thorough evaluation of the individual risk profile in each patient.

Objectives To perform a scoping literature review of cognitive, psychiatric, and quality of life outcomes in adults undergoing extracorporeal membrane oxygenation for any indication. Data sources We searched PubMed, EMBASE, Cochrane Library, Web of Science, CINAHL, and PsycINFO from inception to June 2019. Study selection Observational studies, clinical trials, qualitative studies, and case series with at least 10 adult subjects were included for analysis. Outcomes of interest consisted of general or domain-specific cognition, psychiatric illness, and quality of life measures that included both mental and physical health. Data extraction Study selection, data quality assessment, and interpretation of results were performed by two independent investigators in accordance with the PRISMA statement. Data synthesis Twenty-two articles were included in this review. Six described cognitive outcomes, 12 described psychiatric outcomes of which two were qualitative studies, and 16 described quality of life outcomes. Cognitive impairment was detected in varying degrees in every study that measured it. Three studies examined neuroimaging results and found neurologic injury to be more frequent in venoarterial versus venovenous extracorporeal membrane oxygenation, but described a variable correlation with cognitive impairment. Rates of depression, anxiety, and post-traumatic stress disorder were similar to other critically ill populations and were related to physical disability after extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation survivors' physical quality of life was worse than population norms but tended to improve with time, while mental quality of life did not differ significantly from the general population. Most studies did not include matched controls and instead compared outcomes to previously published values. Conclusions Extracorporeal membrane oxygenation survivors experience cognitive impairment, psychiatric morbidity, and worse quality of life compared with the general population and similar to other survivors of critical illness. Physical disability in extracorporeal membrane oxygenation patients plays a significant role in psychiatric morbidity. However, it remains unclear if structural brain injury plays a role in these outcomes and whether extracorporeal membrane oxygenation causes secondary brain injury.

Background Despite the increased adoption of minimally invasive techniques in colorectal surgery, an open resection with ostomy creation remains an accepted operation for perforated diverticulitis. In the United States, there is an increase in the rates of both morbid obesity and diverticular disease. Therefore, we wanted to explore whether outcomes for morbidly obese patients with diverticulitis are worse than nonmorbidly obese patients after open colectomy for diverticulitis. Materials and methods Using the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2015, we identified adults with emergent admission for diverticulitis (International Classification of Diseases, Ninth Revision, code 562.11) with evidence of preoperative sepsis and intraoperative contaminated/dirty wound classification, in which a resection with ostomy (Current Procedural Terminology codes 44141, 44143, or 44144) was performed. We excluded cases with age >90 y, ventilator dependence, evidence of disseminated cancer and missing sex, race, body mass index, functional status, American Society of Anesthesiologists class, length of stay (LOS), or operative time data. Morbid obesity was defined as body mass index >35 kg/m2. Risk variables of interest included age, sex, race, medical comorbidities, requirement for preoperative transfusion, preoperative sepsis, and operative time. Outcomes of interest included LOS, 30-d postoperative complications, and mortality. Univariate and propensity scores with postmatching analyses were performed. Results A total of 2019 patients met inclusion and exclusion criteria, of which 413 (20.5%) were morbidly obese. Morbidly obese patients tended to be younger (mean 57.2 versus 62.6 y) and female (54.5% versus 45.5%). Morbidly obese patients also had higher rates of insulin-dependent diabetes (8.0% versus 4.2%), hypertension (60.1% versus 51.3%), renal failure (3.4% versus 1.5%), and higher American Society of Anesthesiologists class (class 4: 23.5% versus 19.6% and class 5: 1.45% versus 0.87%). Morbidly obese patient had no increase in 30-d mortality or LOS, but they had higher rates of superficial wound infection (9.0% versus 5.8%; P = 0.0259), deep wound infection (4.4% versus 1.9%; P = 0.0073), acute renal failure (4.8% versus 2.4%; P = 0.0189), postoperative septic shock (17.7% versus 12.1%; P = 0.0040), and return to the operating room (11.1% versus 6.4%; P = 0.0015). We identified 397 morbidly obese patients well matched by propensity score to 397 nonmorbidly obese patients. Conditional logistic regression showed no difference in LOS (median 12.9 versus 12.4 d; P = 0.4648) and no increased risk of 30-d mortality (P = 0.947), but morbid obesity was an independent predictor for return to the operating room (adjusted odds ratio: 27.09 [95% confidence interval: 2.68-274.20]; P = 0.005). Conclusions This analysis of a large national clinical database demonstrates that morbidly obese patients presenting with perforated diverticulitis undergoing a Hartmann's procedure do not have increased mortality or LOS compared with nonobese patients. After adjusting for the effects of morbid obesity, morbidly obese patients had increased risk of return to operating room. Despite literature describing the many perioperative risks of obesity, our analysis showed only increased reoperation for obese patients with diverticulitis.

We investigate techniques for using deep neural networks to produce surrogate models for short-term climate forecasts. A convolutional neural network is trained on 97 years of monthly precipitation output from the 1pctCO2 run (the CO2 concentration increases by 1 % per year) simulated by the second-generation Canadian Earth System Model (CanESM2). The neural network clearly outperforms a persistence forecast and does not show substantially degraded performance even when the forecast length is extended to 120 months. The model is prone to underpredicting precipitation in areas characterized by intense precipitation events. Scheduled sampling (forcing the model to gradually use its own past predictions rather than ground truth) is essential for avoiding amplification of early forecasting errors. However, the use of scheduled sampling also necessitates preforecasting (generating forecasts prior to the first forecast date) to obtain adequate performance for the first few prediction time steps. We document the training procedures and hyperparameter optimization process for researchers who wish to extend the use of neural networks in developing surrogate models.

To demonstrate that repeated episodes of binge drinking during the adolescent period can lead to long-term deficits in motor function and memory in adulthood, and increase proteins in the brain involved with inflammation and apoptotic cell death. Groups of early adolescent (PND 26) and periadolescent (PND 34) Sprague-Dawley rats were exposed to either ethanol or plain air through a vapor chamber apparatus for five consecutive days (2 h per day), achieving a blood ethanol concentration equivalent to 6–8 drinks in the treatment group. Subjects then underwent a series of behavioral tests designed to assess memory, anxiety regulation, and motor function. Brains were collected on PND 94 for subsequent western blot analysis. Behavioral testing using the rota-rod, cage-hang, novel object recognition, light-dark box, and elevated plus maze apparatuses showed significant differences between groups; several of which persisted for up to 60 days after treatment. Western blot testing indicated elevated levels of caspase-3/cleaved caspase-3, NF-kB, and PKC/pPKC proteins in the cerebella of ethanol-treated animals. Differences on anxiety tests indicate a possible failure of behavioral inhibition in the treatment group leading to riskier behavior. Binge drinking also impairs motor coordination and object memory, which involve the cerebellar and hippocampal brain regions, respectively. These experiments indicate the potential dangers of binge drinking while the brain is still developing and indicate the need for future studies in this area.

Background Most studies on endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) for palliation of malignant gastric outlet obstruction (GOO) utilized a 15-mm lumen-apposing metal stent (LAMS). More recently, a 20-mm LAMS has become available. This study aimed to compare rates of technical and clinical success and adverse events (AEs) in patients undergoing EUS-GE using a 20-mm vs. 15-mm LAMS. Methods Patients who underwent EUS-GE with 15-mm or 20-mm LAMS for malignant GOO during the period from January 2018 to October 2020 were included. The primary outcome was clinical success, defined as an increase in the gastric outlet obstruction score (GOOS) by at least 1 point during follow-up. Secondary outcomes were technical success, maximum tolerated diet, re-intervention rate, and rate/severity of AEs. Results 267 patients (mean age 67 years, 43 % women) with malignant GOO from 19 centers underwent EUS-GE. Clinical success rates were similar for the 15-mm and 20-mm stents (89.2 % [95 %CI 84.2 %–94.2 %] vs. 84.1 % [77.4%–90.6 %], respectively). However, a significantly higher proportion of patients in the 20-mm group tolerated a soft solid/complete diet at the end of follow-up (91.2 % [84.4 %–95.7 %] vs. 81.2 % [73.9 %–87.2 %], P = 0.04). Overall, AEs occurred in 33 patients (12.4 % [8.4 %–16.3 %]), with similar rates for 15-mm and 20-mm stents (12.8 % [7.5 %–18.2 %] vs. 11.8 % [6 %–17.6 %]), including incidence of severe/fatal AEs (2 % [0.4 %–5.8 %] vs. 3.4 % [0.9 %–8.4 %]). Conclusions The 20-mm and 15-mm LAMS show similar safety and efficacy for patients undergoing EUS-GE for malignant GOO. The 20-mm LAMS allows a more advanced diet and is, thus preferred for EUS-GE.

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy Body Dementia (LBD), which includes Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer pathology as well as novel biomarkers were discussed.

Background and Aims Stent misdeployment (SM) has hindered the dissemination of EUS-guided gastroenterostomy (EUS-GE) for gastric outlet obstruction (GOO) management. We aimed to provide a classification system for SM during EUS-GE and study clinical outcomes and management accordingly. Methods This is a retrospective study involving 16 tertiary care centers (8 in the United States, 8 in Europe) from March 2015 to December 2020. Patients who developed SM during EUS-GE for GOO were included. We propose classifying SM into 4 types. The primary outcome was rate and severity of SM (per American Society for Gastrointestinal Endoscopy lexicon), whereas secondary outcomes were clinical outcomes and management of dislodgement according to the SM classification type, in addition to salvage management of GOO after SM. Results From 467 EUS-GEs performed for GOO during the study period, SM occurred in 46 patients (9.85%). Most SMs (73.2%) occurred during the first 13 EUS-GE cases by the performing operators. SM was graded as mild (n = 28, 60.9%), moderate (n = 11, 23.9%), severe (n = 6, 13.0%), or fatal (n = 1, 2.2%), with 5 patients (10.9%) requiring surgical intervention. Type I SM was the most common (n = 29, 63.1%), followed by type II (n = 14, 30.4%), type IV (n = 2, 4.3%), and type III (n = 1, 2.2%). Type I SM was more frequently rated as mild compared with type II SM (75.9% vs 42.9%, P = .04) despite an equivalent rate of surgical repair (10.3% vs 7.1%, P = .7). Overall, 4 patients (8.7%) required an intensive care unit stay (median, 2.5 days). The median length of stay was 4 days after SM. Conclusions Although SM is not infrequent during EUS-GE, most are type I, mild/moderate in severity, and can be managed endoscopically with a surgical intervention rate of approximately 11%.

Background Mycophenolate mofetil (MMF) plays an increasingly important role in the treatment of children with nephrotic syndrome, especially in steroid sparing protocols. Recent publications show the relationship of exposure to its active moiety mycophenolic acid (MPA) and clinical efficacy. Performance of full-time pharmacokinetic (PK) profiles, however, is inconvenient and laborious. Established limited sampling strategies (LSS) to estimate the area under the concentration (AUC) versus time curve of MPA (MPA-AUC) in pediatric renal transplant recipients cannot be easily transferred to children suffering from nephrotic syndrome, mainly because of the lack of concomitant immunosuppressive therapy. We therefore aimed for the generation and validation of a LSS to estimate MPA exposure to facilitate therapeutic drug monitoring in children with nephrotic syndrome. Methods We performed 27 complete PK profiles in 23 children in remission [mean age (±SD):12.3 ± 4.26 years] to generate and validate an LSS. Sampling time points were before administration (C0) and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours after the administration of MMF. MPA was measured by enzyme multiplied immunoassay technique. There was no concomitant treatment with calcineurin inhibitors. Results Mean daily dose of MMF was 927 ± 209 mg/m of body surface area resulting in a mean MPA-AUC0-12 value of 59.2 ± 29.3 mg × h/L and a predose level of 3.03 ± 2.24 mg/L. Between-patient variability of dose-normalized MPA-AUC0-12 was high (coefficient of variation: 45.5%). Correlation of predose levels with the corresponding MPA-AUC0-12 was moderate (r = 0.59) in a subgroup of 18 patients (20 PK profiles, generation group). An algorithm based on 3 PK sampling time points during the first 2 hours after MMF dosing (estimated AUC0-12 = 8.7 + 4.63 × C0 + 1.90 × C1 + 1.52 × C2) was able to predict MPA-AUC with a low percentage prediction error (3.88%) and a good correlation of determination (r = 0.90). Validation of this algorithm in a randomized separate group of 6 patients (7 PK profiles, validation group) resulted in comparably good correlation (r = 0.95) and low percentage prediction error (5.57%). Conclusions An abbreviated profile within the first 2 hours after MMF dosing gives a good estimate of MPA exposure in children with nephrotic syndrome and hence has the potential to optimize MMF therapy.

Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia and usually responds well to steroids. However, relapses are frequent, which can require multi-drug therapy with deleterious long-term side effects. In the last decades, different hypotheses on molecular mechanisms underlying INS have been proposed and several lines of evidences strongly indicate a crucial role of the immune system in the pathogenesis of non-genetic INS. INS is traditionally considered a T-cell-mediated disorder triggered by a circulating factor, which causes the impairment of the glomerular filtration barrier and subsequent proteinuria. Additionally, the imbalance between Th17/Tregs as well as Th2/Th1 has been implicated in the pathomechanism of INS. Interestingly, B-cells have gained attention, since rituximab, an anti-CD20 antibody demonstrated a good therapeutic response in the treatment of INS. Finally, recent findings indicate that even podocytes can act as antigen-presenting cells under inflammatory stimuli and play a direct role in activating cellular pathways that cause proteinuria. Even though our knowledge on the underlying mechanisms of INS is still incomplete, it became clear that instead of a traditionally implicated cell subset or one particular molecule as a causative factor for INS, a multi-step control system including soluble factors, immune cells, and podocytes is necessary to prevent the occurrence of INS. This present review aims to provide an overview of the current knowledge on this topic, since advances in our understanding of the immunopathogenesis of INS may help drive new tailored therapeutic approaches forward.

Background: White matter (WM) damage is a consistent finding in HIV-infected (HIV+) individuals. Previous studies have evaluated WM fiber tract-specific brain regions in HIV-associated neurocognitive disorders (HAND) using diffusion tensor imaging (DTI). However, DTI might lack an accurate biological interpretation, and the technique suffers from several limitations. Fixel-based analysis (FBA) and free water corrected DTI (fwcDTI) have recently emerged as useful techniques to quantify abnormalities in WM. Here, we sought to evaluate FBA and fwcDTI metrics between HIV+ and healthy controls (HIV−) individuals. Using machine learning classifiers, we compared the specificity of both FBA and fwcDTI metrics in their ability to distinguish between individuals with and without cognitive impairment in HIV+ individuals.Methods: Forty-two HIV+ and 52 HIV– participants underwent MRI exam, clinical, and neuropsychological assessments. FBA metrics included fiber density (FD), fiber bundle cross section (FC), and fiber density and cross section (FDC). We also obtained fwcDTI metrics such as fractional anisotropy (FAT) and mean diffusivity (MDT). Tract-based spatial statistics (TBSS) was performed on FAT and MDT. We evaluated the correlations between MRI metrics with cognitive performance and blood markers, such as neurofilament light chain (NfL), and Tau protein. Four different binary classifiers were used to show the specificity of the MRI metrics for classifying cognitive impairment in HIV+ individuals.Results: Whole-brain FBA showed significant reductions (up to 15%) in various fiber bundles, specifically the cerebral peduncle, posterior limb of internal capsule, middle cerebellar peduncle, and superior corona radiata. TBSS of fwcDTI metrics revealed decreased FAT in HIV+ individuals compared to HIV– individuals in areas consistent with those observed in FBA, but these were not significant. Machine learning classifiers were consistently better able to distinguish between cognitively normal patients and those with cognitive impairment when using fixel-based metrics as input features as compared to fwcDTI metrics.Conclusion: Our findings lend support that FBA may serve as a potential in vivo biomarker for evaluating and monitoring axonal degeneration in HIV+ patients at risk for neurocognitive impairment.

In May 2021, the Alpha variant (B.1.1.7) of SARS-CoV-2 was found in 91% of the SARS-CoV-2 cases in Germany. Not much is known about the symptoms, courses of disease, and infectiousness in pediatric patients with the Alpha variant. Objective: The aim of this retrospective analysis was to gain information on the infection with the Alpha variant in children and adolescents. Methods: Between 12 January 2021 and 3 June 2021, all nucleic acid amplification tests (NAATs) of children who received a swab for SARS-CoV-2 were included. Data were collected on standardized questionnaires. The analysis of data was anonymized and retrospective. Results: We investigated 3544 NAATs, 95 children were tested positive (2.7%) for SARS-CoV-2. For the sub-analysis, 65 children were analyzed. In 59 children, the Alpha variant was found (90.8%), and 54.2% (n = 32/59) were symptomatic. The most common symptoms were fever, cough, and rhinitis. The median Ct value was 24.0 (min 17.0, max 32.7). Conclusions: We can underline early findings that children are still less effected by SARS-CoV-2 infection with the spread of the Alpha variant. We found no evidence that children infected with the Alpha variant showed more severe symptoms or suffered from a more severe clinical course than those infected with the wild type.

PubMedID: 31038179 Background: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment. Methods: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ?8 mL/min/1.73 m2 (early starters) and eGFR

Objective To compare blood lead levels in females of childbearing age, 12-50 years, living within and adjacent to Flint, Michigan, before, during, and after the Flint River water exposure and compare the levels to those that have been shown to cause fetal loss and preterm birth. Methods The switch in the community water source to the Flint River occurred on April 25, 2014, and was reverted to the original source on October 15, 2015. Using a retrospective cross-sectional study design using geocoded blood lead levels obtained from all females of childbearing age available from a single hospital database, we compared blood lead levels for the following 18-month time periods: April 25, 2012-October 15, 2013 (PRE), April 25, 2014-October 15, 2015 (DURING), and April 25, 2016-October 15, 2017 (POST). Results Results are reported as geometric mean (95% CI). Within Flint, PRE blood lead levels in females of childbearing age were 0.69 micrograms/dL (95% CI 0.63-0.75), DURING blood lead levels were 0.65 micrograms/dL (95% CI 0.60-0.71), and POST blood lead levels were 0.55 micrograms/dL (95% CI 0.54-0.56). DURING Flint River water exposure blood lead levels were not significantly different than the PRE Flint River water time period. POST Flint River water exposure blood lead levels were significantly lower than both PRE and DURING levels. Overall, lower blood lead levels were found outside the Flint boundary in all cohorts. Conclusion Blood lead levels in Flint females of childbearing age did not increase during the Flint River water exposure and subsequent 18-month time period. Mean blood lead levels during the Flint River water exposure are not consistent with the markedly higher blood lead levels reported in the literature to be associated with fetal loss, low birth weight, or preterm birth.

Das nephrotische Syndrom (NS) im Kindesalter erfullt die Kriterien einer seltenen Erkrankung, und doch ist es die haufigste Glomerulopathie in dieser Altersgruppe. Gleichzeitig ist es eine heterogene Erkrankung, die durch die Kategorien Alter bei Erstmanifestation, Atiologie, Histologie und Ansprechen auf eine Standardtherapie mit Glukokortikoiden eingeteilt werden kann. Das primare Ansprechen auf eine Standardtherapie mit Glukokortikoiden differenziert zwischen steroidsensiblem (SSNS) und steroidresistentem NS (SRNS) und ist der wichtigste Prognosefaktor. Eine hohe kumulative Dosis an Glukokortikoiden (Steroiden) oder die verlangerte Gabe bei Behandlung der Erstmanifestation beeinflussen das Rezidivrisiko nicht. Eine molekulargenetische Abklarung bei Patienten mit SRNS ist zur Vermeidung einer wirkungslosen immunsuppressiven Therapie dringend zu empfehlen. Der vorliegende Text gibt eine Ubersicht zur Therapie des NS, beleuchtet Unterschiede in der Diagnostik und Therapie im Kindes- und Erwachsenenalter und beschreibt Risiken und Langzeitfolgen der Therapie. Haufige Rezidive des NS und das SRNS stellen weiterhin eine therapeutische Herausforderung dar. Der Einsatz von Steroiden und einer immunsuppressiven Erhaltungstherapie hat erhebliche Langzeitauswirkungen. Die optimale Behandlung von Patienten mit SSNS mit seltenen Rezidiven im Erwachsenenalter ist unklar.

Childhood steroid-dependent (SDNS) and frequently relapsing (FRNS) nephrotic syndromes often require long-term immunosuppressive therapy to maintain remission. Successful discontinuation of maintenance therapy remains to be a challenge with these children. In the following article, we report our experience on patients after discontinuation of steroid-sparing immunosuppressive maintenance therapy (IT). Thereby, we retrospectively reviewed all patients between 2006 and 2016 with a relapsing course of steroid-sensitive nephrotic syndrome (SDNS or FRNS) treated with steroid-sparing maintenance immunosuppressive medication. Patient data of a total of 24 patients were recorded for a median time of 53.5 (11.2 - 112) months. In 11 patients, therapy was discontinued at physician's discretion. Thereafter, 8 of 11 patients (group A) relapsed after a median time of 2.21 (0.23 - 9.17) months, and IT was restarted. The remaining 3 patients (group B) maintained in long-term remission for a median time of 26.9 (17.7 - 32.1) months until the end of observation. Neither age, at initial episode nor at discontinuation or duration of IT, differed significantly between the groups of patients with relapse after discontinuation of IT, compared to those without. There was a trend towards a shorter relapse-free interval before discontinuation in group A than in group B (35.7 vs. 44.1 months). All patients who restarted IT again attained a stable remission until the last follow-up and did not show any further relapse. These results demonstrate that a failed discontinuation attempt does not put the patient's future remission at risk. .

Background & Aims Patients with inflammatory bowel disease (IBD) alter their dietary behaviors to reduce disease-related symptoms, avoid feared food triggers, and control inflammation. This study aimed to estimate the prevalence of avoidant/restrictive food intake disorder (ARFID), evaluate risk factors, and examine the association with risk of malnutrition in patients with IBD. Methods This cross-sectional study recruited adult patients with IBD from an ambulatory clinic. ARFID risk was measured using the Nine-Item ARFID Screen. Nutritional risk was measured with the Patient Generated-Subjective Global Assessment. Logistic regression models were used to evaluate the association between clinical characteristics and a positive ARFID risk screen. Patient demographics, disease characteristics, and medical history were abstracted from medical records. Results Of the 161 participants (Crohn’s disease, 45.3%; ulcerative colitis, 51.6%; IBD-unclassified, 3.1%), 28 (17%) had a positive ARFID risk score (≥24). Most participants (92%) reported avoiding 1 or more foods while having active symptoms, and 74% continued to avoid 1 or more foods even in the absence of symptoms. Active symptoms (odds ratio, 5.35; 95% confidence interval, 1.91–15.01) and inflammation (odds ratio, 3.31; 95% confidence interval, 1.06–10.29) were significantly associated with positive ARFID risk. Patients with a positive ARFID risk screen were significantly more likely to be at risk for malnutrition (60.7% vs 15.8%; P Conclusions Avoidant eating behaviors are common in IBD patients, even when in clinical remission. Patients who exhibit active symptoms and/or inflammation should be screened for ARFID risk, with referrals to registered dietitians to help monitor and address disordered eating behaviors and malnutrition risk.

Malignancy and surgery are both independent risk factors for venous thromboembolism (VTE) events. The current NCCN guidelines recommend VTE prophylaxis for up to 28 days after major abdominal or pelvic surgery for malignancy. We set out to evaluate the rate and timing of VTEs among patients with gastric, pancreatic, colorectal, and gynecologic malignancies who underwent surgery. We performed a retrospective review of the NSQIP database (2005–2013) focusing on patients with gastric, colorectal, pancreatic, and gynecologic malignancies. Our primary endpoint was a diagnosis of VTE within 30 days of surgery. We analyzed 128,864 patients in this study. On multivariable analysis, patients with pre-operative sepsis (OR 2.36, CI 2.04–2.76, p

Background White matter (WM) damage is a consistent finding in HIV infected (HIV+) individuals. Previous studies have evaluated WM fiber tract specific brain regions in HIV-associated neurocognitive disorders (HAND) using conventional diffusion tensor imaging (DTI). However, DTI might lack an accurate biological interpretation, and the technique suffers from several limitations. Fixel-based analysis (FBA) and free water corrected DTI (fwcDTI) have recently emerged as useful techniques to quantify abnormalities in WM. Here, we sought to evaluate FBA and fwcDTI metrics between HIV+ and HIV-individuals. Using machine learning classifiers, we compared the specificity of both FBA and fwcDTI metrics in their ability to distinguish between individuals with and without cognitive impairment. Methods Forty-two HIV+ and 52 HIV-participants underwent MRI exam, clinical and neuropsychological assessments. FBA metrics included fiber density (FD), fiber bundle cross-section (FC), and fiber density and cross-section (FDC). We also obtained fwcDTI metrics such as fractional anisotropy (FAT) and mean diffusivity (MDT). Tract-based spatial statistics (TBSS) was performed on FAT and MDT. We evaluated the correlations between MRI metrics with cognitive performance and blood markers, such as neurofilament light chain NfL, and Tau protein. Statistical significance was evaluated at α = 0.05. Four different binary classifiers were used to show the specificity of the MRI metrics for classifying cognitive impairment in HIV+ individuals. Results Whole brain FBA showed significant reductions (up to 15%) in various fiber bundles, specifically, the cerebral peduncle, posterior limb of internal capsule, middle cerebellar peduncle and superior corona radiata. TBSS of fwcDTI metrics revealed decreased FAT (by 1-2%) in HIV+ individuals compared to HIV-individuals in areas consistent with those observed in FBA, but these were not significant. An adaptive boosting binary classifier reliably distinguished between cognitively normal patients and those with cognitive impairment with 80% precision and 78% recall. The mean area under the curve (AUC) was 0.805 ± 0.093 for the receiver operatic characteristic (ROC) curve, and 0.859 ± 0.133 for the precision-recall curve, using five-fold cross validation. Conclusion Our findings lend support that FBA may serve as a potential in vivo biomarker for evaluating and monitoring patients with HIV at risk for neurocognitive impairment, and emphasizes the importance of utilizing more complex diffusion models in evaluating HIV infection.

Initiation of combination antiretroviral therapy (cART) reduces inflammation in HIV-infected (HIV+) individuals. Recent studies demonstrated that diffusion MRI based extracellular free water (FW) modeling can be sensitive to neuroinflammation. Here, we investigate the FW in HIV-infection, its temporal evolution, and its association with blood markers, and cognitive scores. Using 96 age-matched participants, we found that FW was significantly elevated in grey and white matter in cART-naïve HIV+ compared to HIV-uninfected (HIV−) individuals at baseline. These increased FW values positively correlated with neurofilament light chain (NfL) and negatively correlated with CD4 counts. FW in grey and white matter, as well as NfL decreased in the HIV+ after 12 weeks of cART treatment. No significant FW differences were noted between the HIV+ and HIV− cohorts at 1 and 2-year follow-up. Results suggest that FW elevation in cART-naïve HIV+ participants is likely due to neuroinflammation. The correlation between FW and NfL, and the improvement in both FW and NfL after 12 weeks of cART treatment further reinforces this conclusion. The longer follow-up at 1 and 2 years suggests that cART helped control neuroinflammation as inferred by FW. Therefore, FW could be used as a biomarker to monitor HIV-associated neuroinflammation.

Perimenopause is associated with declines in attention, working memory and verbal memory; however, there are significant individual differences. Further, the contributions of hormones and menopausal symptoms to domain-specific cognitive functions remain unknown. This longitudinal study aimed to determine whether there were distinct cognitive profiles in perimenopause and to identify factors associated with each profile.In a sample of 85 women evaluated over 400 bi-annual visits, we administered a comprehensive neuropsychological battery, assessed menopausal symptoms and measured 17β-estradiol and follicle stimulating hormone. Multilevel latent profile analysis was used to identify cognitive profiles. Regressions were conducted to determine differences in hormones and symptoms by profile after adjusting for Stages of Reproductive Aging Workshop + 10 (STRAW + 10) stage and demographic factors.Perimenopausal cognitive profiles consisted of cognitively normal (Profile 1;There is significant heterogeneity in cognition during perimenopause. While most women do not develop impairments, a significant minority experience weaknesses in verbal learning and memory. Profile analysis may identify at-risk populations and inform interventions.

Congenital anomalies of the kidney and urinary tract (CAKUT) occur in 0.5–1/100 newborns and as a group they represent the most frequent cause for chronic kidney failure in children. CAKUT comprise clinically heterogeneous conditions, ranging from mild vesicoureteral reflux to kidney aplasia. Most forms of CAKUT share the pathophysiology of an impaired developmental interaction of the ureteric bud (UB) and the metanephric mesenchyme (MM). In most cases, CAKUT present as an isolated condition. They also may occur as a component in rare multi-organ syndromes. Many CAKUT probably have a multifactorial etiology. However, up to 20% of human patients and > 200 transgenic mouse models have a monogenic form of CAKUT, which has fueled our efforts to unravel molecular kidney (mal-)development. To date, genetic variants in more than 50 genes have been associated with (isolated) CAKUT in humans. In this short review, we will summarize typical imaging findings in patients with CAKUT and highlight recent mechanistic insight in the molecular pathogenesis of monogenic forms of CAKUT. Supplementary Information The online version contains supplementary material available at 10.1186/s40348-021-00112-0.

Background Chronic kidney disease (CKD) still leads to high mortality rates, mainly due to cardiovascular disease. One important influencing factor is persisting low-grade chronic inflammation partly maintained by gingivitis that favors transient bacteremia during daily activities such as toothbrushing. Methods To examine whether intensive dental prophylaxis can restore oral health, reduce the prevalence of bacteremia and degree of systemic inflammation indicated by CRP levels, we conducted this pilot study examining 30 CKD patients aged 6–26 years, 15 receiving intensive prophylaxis (IP), 15 receiving treatment as usual (TAU) serving as control group. There were three appointments for examination, each 10 ± 1 weeks apart (at baseline, after intervention periods one and two, when TAU also received IP, and the IP group stopped prophylaxis). Results The gingival index (GI) in the IP group decreased by 90% (GI 0.09; p=0.001), resulting in almost healthy gingiva. There was no significant change in CRP or prevalence of bacteremia. General prevalence of bacteremia after toothbrushing was 9.5% affecting 7 (26%) of the participants. In three participants, bacteremia dissolved after IP, in one after TAU. Two patients developed bacteremia ≥ 10 weeks after ending IP. We identified eight different bacterial species. Conclusions We were able to show that IP can effectively treat gingivitis. It might be a promising approach to reduce systemic inflammation and subsequently lower premature cardiovascular disease, despite the lack of statistical significance. Future research requires a larger patient cohort to enable matched treatment groups with long-term follow-up and molecular detection methods for bacteremia. Graphical abstract

Background The impact of intraoperative frozen section (iFS) analysis on the frequency of completion thyroidectomy for the management of thyroid carcinoma is controversial. Although specialized endocrine centres have published their respective results, there are insufficient data from primary and secondary healthcare levels. The aim of this study was to analyse the utility of iFS analysis. Methods In the Prospective Evaluation Study Thyroid Surgery (PETS) 2 study, 22 011 operations for benign and malignant thyroid disease were registered prospectively in 68 European hospitals from 1 July 2010 to 31 December 2012. Group 1 consisted of 569 patients from University Medical Centre (UMC) Mainz, and group 2 comprised 21 442 patients from other PETS 2 participating hospitals. UMC Mainz exercised targeted but liberal use of iFS analysis for suspected malignant nodules. iFS analysis was compared with standard histological examination regarding the correct distinction between benign and malignant disease. The percentage of completion thyroidectomies was assessed for the participating hospitals. Results iFS analysis was performed in 35.70 per cent of patients in group 1 versus 21.80 per cent of those in group 2 (risk ratio (RR) 1.6, 95 per cent c.i. 1.5 to 1.8; P, Intraoperative frozen-section (iFS) analysis is discussed critically in the current literature, lacking a definite conclusion. Yet, the clinical value of iFS analysis for the surgical management of malignant thyroid disease is illustrated by this multicentre retrospective study.

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence.

Idiopathic nephrotic syndrome is the most frequent glomerular disease in children in most parts of the world. Children with steroid-sensitive nephrotic syndrome (SSNS) generally have a good prognosis regarding the maintenance of normal kidney function even in the case of frequent relapses. The course of SSNS is often complicated by a high rate of relapses and the associated side effects of repeated glucocorticoid (steroid) therapy. The following recommendations for the treatment of SSNS are based on the comprehensive consideration of published evidence by a working group of the German Society for Pediatric Nephrology (GPN) based on the systematic Cochrane reviews on SSNS and the guidelines of the KDIGO working group (Kidney Disease - Improving Global Outcomes). Supplementary Information The online version contains supplementary material available at 10.1007/s00467-021-05135-3.

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Introduction: Kidney biopsy remains the gold standard for the diagnosis of most renal diseases. A major obstacle to performing a biopsy is safety concerns. However, many safety measures are not evidence based and therefore vary widely between centers. We sought to determine the rate and timing of kidney biopsy complications in our center, to compare the complication rate between native and transplant kidney biopsies, to evaluate the feasibility of performing kidney biopsies as an outpatient procedure and the value of a postbiopsy ultrasound before discharge, and to identify risk factors for complications. Methods: We performed a single-center, retrospective, observational study at the Division of Nephrology of the University Hospital Zurich including all patients who underwent renal biopsy between January 2005 and December 2017. Major bleeding (primary outcome) and any other bleeding or nonbleeding complications (secondary outcomes) were compared between native and transplant kidney biopsies and between inpatient and outpatient procedures and correlated with clinical factors possibly affecting bleeding risk. Results: Overall, 2,239 biopsies were performed in 1,468 patients, 732 as inpatient and 1,507 as outpatient procedures. Major bleeding was observed in 28 (3.8%) inpatient and in 15 (1.0%) outpatient procedures, totaling to 43 (1.9%) of all biopsies. Major bleeding requiring intervention amounted to 1.0% (0.5% of outpatient procedures). Rate of major bleeding was similar between native and transplant kidneys. 13/15 (87%) bleeding episodes in planned outpatient procedures were detected during the 4-h surveillance period. Risk factors for bleeding were aspirin use, low eGFR, anemia, cirrhosis, and amyloidosis. Routine postbiopsy ultrasound did not change management. Conclusions: Kidney biopsy is an overall safe procedure and can be performed as an outpatient procedure in most patients with an observation period as short as 4 h. The value of routine postbiopsy ultrasound is questionable.

Background & Aims Conventional endoscopic mucosal resection (CEMR) with submucosal injection is the current standard for the resection of large, nonmalignant colorectal polyps. We investigated whether underwater endoscopic mucosal resection (UEMR) is superior to CEMR for large (20–40mm) sessile or flat colorectal polyps. Methods In this prospective randomized controlled study, patients with sessile or flat colorectal polyps between 20 and 40 mm in size were randomly assigned to UEMR or CEMR. The primary outcome was the recurrence rate after 6 months. Secondary outcomes included en bloc and R0 resection rates, number of resected pieces, procedure time, and adverse events. Results En bloc resection rates were 33.3% in the UEMR group and 18.4% in the CEMR group (P = .045); R0 resection rates were 32.1% and 15.8% for UEMR vs CEMR, respectively (P = .025). UEMR was performed with significantly fewer pieces compared to CEMR (2 pieces: 45.5% UEMR vs 17.7% CEMR; P = .001). The overall recurrence rate did not differ between both groups (P = .253); however, subgroup analysis showed a significant difference in favor of UEMR for lesions of >30 mm to ≤40 mm in size (P = .031). The resection time was significantly shorter in the UEMR group (8 vs 14 minutes; P Conclusions UEMR is superior to CEMR regarding en bloc resection, R0 resection, and procedure time for large colorectal lesions and shows significantly lower recurrence rates for lesions >30 mm to ≤40 mm in size. UEMR should be considered for the endoscopic resection of large colorectal polyps.

Contains fulltext : 231550.pdf (Publisher’s version ) (Closed access) Introduction: Mycophenolate mofetil (MMF) is an ester prodrug of the immunosuppressant mycophenolic acid (MPA) and is recommended and widely used for maintenance immunosuppressive therapy in solid organ and stem-cell transplantation as well as in immunological kidney diseases. MPA is a potent, reversible, noncompetitive inhibitor of the inosine monophosphate dehydrogenase (IMPDH), a crucial enzyme in the de novo purine synthesis in T- and B-lymphocytes, thereby inhibiting cell-mediated immunity and antibody formation. The use of therapeutic drug monitoring (TDM) of MMF is still controversial as outcome data of clinical trials are equivocal. Areas covered: This review covers in great depth the existing literature on TDM of MMF in the field of pediatric (kidney) transplantation. In addition, the relevance of TDM in immunological kidney diseases, in particular childhood nephrotic syndrome is highlighted. Expert opinion: TDM of MMF has the potential to optimize therapy in pediatric transplantation as well as in nephrotic syndrome. Limited sampling strategies to estimate MPA exposure increase its feasibility. Future perspectives rather encompass approaches reflecting total immunosuppressive load than single drug TDM.

Highlights • cART naïve HIV + patients have reduced basal ganglia glutamate levels that improved after 12 weeks of treatment. • Glutamate levels were inversely correlated with plasma levels of neurofilament light chain. • Metabolite and blood biomarkers of neuronal damage were stable over a two-year follow up. • Our results suggest there was no cART neurotoxicity effect in this relatively young cohort of HIV + individuals., The aim of this study was to quantify, via Magnetic Resonance Spectroscopy (MRS), the effect of combination antiretroviral therapy (cART) on brain metabolites and characterize any possible associations between changes in metabolites, age, blood biomarkers of neuronal damage, functional connectivity and cognitive performance. As cART has dramatically increased the life expectancy of HIV-infected (HIV + ) individuals and unmasked an increase in HIV-associated neurocognitive disorders, it is still not clear whether cART neurotoxicity contributes to these disorders. We hypothesized a bimodal effect, with early cART treatment of HIV infection decreasing inflammation as measured by MRS metabolites and improving cognitive performance, and chronic exposure to cART contributing to persistence of cognitive impairment via its effect on mitochondrial function. Basal ganglia metabolites, functional connectivity, cognitive scores, as well as plasma levels of neurofilament light chain (NfL) and tau protein were measured before and after 12 weeks, 1 year and 2 years of cART in a cohort of 50 cART-naïve HIV + subjects and 72 age matched HIV- healthy controls. Glutamate (Glu) levels were lower in the cART naïve patients than in healthy controls and were inversely correlated with plasma levels of NfL. There were no other significant metabolite differences between HIV + and uninfected individuals. Treatment improved Glu levels in HIV+, however, no associations were found between Glu, functional connectivity and cognitive performance. Stable brain metabolites and plasma levels of NfL and Tau over two-years of follow-ups suggest there are no signs of cART neurotoxicity in this relatively young cohort of HIV + individuals.