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The goal of the qNMR Summit is to take stock of the status quo and the recent developments in qNMR research and applications in a timely and accurate manner. It provides a platform for both advanced and novice qNMR practitioners to receive a well-rounded update and discuss potential qNMR-related applications and collaborations. For over a decade, scientists from academia, industry, nonprofit institutions, and governmental bodies have focused on the standardization of qNMR methodology, as well as its metrological and pharmacopeial utility. This paper reviews key content of qNMR Summits 1.0 to 4.0 and puts into perspective the outcomes and available transcripts of the October 2019 Summit 5.0, with attendees from the United States, Canada, Japan, Korea, and several European countries. Summit presentations focused on qNMR methodology in the pharmaceutical industry, advanced quantitation algorithms, and promising developments.

Hypotension, blood pressure fluctuation, and endothelial impairment indicate possible additive pathophysiological aspects in the development of posterior reversible encephalopathy syndrome in children on peritoneal dialysis.

Extracts of red clover (Trifolium pratense L.), containing estrogenic isoflavones like genistein and daidzein and the proestrogenic isoflavones formononetin and biochanin A, are used by women as dietary supplements for the management of menopausal symptoms. Although marketed as a safer alternative to hormone therapy, red clover isoflavones have been reported to inhibit some cytochrome P450 (CYP) enzymes involved in drug metabolism. To evaluate the potential for clinically relevant drug-red clover interactions, we tested a standardized red clover dietary supplement (120 mg isoflavones per day) for interactions with the pharmacokinetics of four FDA-approved drugs (caffeine, tolbutamide, dextromethorphan, and alprazolam) as probe substrates for the enzymes CYP1A2, CYP2C9; CYP2D6, and CYP3A4/5, respectively. Fifteen peri- and post-menopausal women completed pharmacokinetic studies at baseline and 2 weeks after consuming red clover. The averaged pharmacokinetic profiles of probe substrates in serum showed no significant alterations and no changes in the areas under the curve (AUC) over 96 h. Subgroup analysis based on the demographic characteristics (BMI, menopausal status, race, and age) also showed no differences in AUC for each probe substrate. Analysis of red clover isoflavones in serum showed primarily conjugated metabolites that explain, at least in part, the red clover pharmacokinetic safety profile.

The kidneys and the urinary tract are a common source of infection in children of all ages, especially infants and young children. The main risk factors for sequelae after urinary tract infections (UTI) are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction. UTI should be considered in every child with fever without a source. The differentiation between upper and lower UTI is crucial for appropriate management. Method of urine collection should be based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. Treatment of UTI should be based on practical considerations regarding age and presentation with adjustment of the initial antimicrobial treatment according to antimicrobial sensitivity testing. All children, regardless of age, should have an ultrasound of the urinary tract performed after pyelonephritis. In general, antibiotic prophylaxis is not recommended.Conclusion: Based on recent data and in line with international guidelines, multidisciplinary Swiss consensus recommendations were developed by members of Swiss pediatric infectious diseases, nephrology, and urology societies giving the clinician clear recommendations in regard to diagnosis, type and duration of therapy, antimicrobial treatment options, indication for imaging, and antibiotic prophylaxis.What is Known:•Urinary tract infections (UTI) are a common and important clinical problem in childhood. Although children with pyelonephritis tend to present with fever, it can be difficult on clinical grounds to distinguish cystitis from pyelonephritis, particularly in young children less than 2 years of age.•Method of urine collection is based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture.What is New:•Vesicoureteric reflux (VUR) remains a risk factor for UTI butper seis neither necessary nor sufficient for the development of renal scars. Congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction play a more important role as causes of long-term sequelae. In general, antibiotic prophylaxis is not recommended.•A switch to oral antibiotics should be considered already in young infants. Indications for invasive imaging are more restrictive and reserved for patients with abnormal renal ultrasound, complicated UTI, and infections with pathogens other than E. coli.

Objective: This meta-analysis evaluated the effect of dry needling alone or combined with other treatment interventions on pain, related-disability, pressure pain sensitivity, and strength in people with lateral epicondylalgia of musculoskeletal origin. Data Sources: MEDLINE, CINAHL, PubMed, PEDro, Cochrane Library, SCOPUS and Web of Science databases from their inception to 5 April 2020. Review Methods: Randomized controlled trials collecting outcomes on pain, related-disability, pressure pain thresholds, or strength where one group received dry needling for lateral epicondylalgia of musculoskeletal origin. The risk of bias was assessed by the Cochrane Guidelines, methodological quality was assessed with the PEDro score, and the quality of evidence by using the GRADE approach. Results: Seven studies including 320 patients with lateral epicondylalgia were included. The meta-analysis found that dry needling reduced pain intensity (SMD ‒1.13, 95%CI ‒1.64 to ‒0.62) and related-disability (SMD ‒2.17, 95%CI ‒3.34 to ‒1.01) with large effect sizes compared to a comparative group. Dry needling also increased pressure pain thresholds with a large effect size (SMD 0.98, 95%CI 0.30 to 1.67) and grip strength with a small size effect (SMD 0.48, 95%CI 0.16 to 0.81) when compared to a comparative group. The most significant effect was at short-term. The risk of bias was generally low, but the heterogenicity of the results downgraded the evidence level. Conclusion: Low to moderate evidence suggests a positive effect of dry needling for pain, pain-related disability, pressure pain sensitivity and strength at short-term in patients with lateral epicondylalgia of musculoskeletal origin. Level of Evidence: Therapy, level 1a. Registration number: OSF Registry - https://doi.org/10.17605/OSF.IO/ZY3E8

Background A potential mechanism of action of manual therapy is the activation of a sympathetic-excitatory response. Objective To evaluate the effects of joint mobilisation on changes in clinical manifestations of sympathetic nervous system activity. Data sources MEDLINE, EMBASE, AMED, CINAHL, EBSCO, PubMed, PEDro, Cochrane Collaboration Trials Register, Cochrane Database of Systematic Reviews and SCOPUS databases. Study selection Randomised controlled trials that compared a mobilisation technique applied to the spine or the extremities with a control or placebo. Data extraction and data synthesis Human studies collecting data on skin conductance or skin temperature were used. Data were extracted by two reviewers. Risk of bias was assessed using the Cochrane guidelines, and quality of evidence was assessed using the GRADE approach. Standardised mean differences (SMD) and random effects were calculated. Results Eighteen studies were included in the review and 17 were included in the meta-analysis. The meta-analysis found a significant increase in skin conductance [SMD 1.21, 95% confidence interval (CI) 0.88 to 1.53, n = 269] and a decrease in temperature (SMD 0.92, 95% CI −1.47 to −0.37, n = 128) after mobilisation compared with the control group. An increase in skin conductance (SMD 0.73, 95% CI 0.51 to 0.96, n = 293) and a decrease in temperature (SMD −0.50, 95% CI −0.82 to −0.18, n = 134) were seen after mobilisation compared with placebo. The risk of bias was generally low, but the heterogenicity of the results downgraded the level of evidence. Limitations Most trials (14/18) were conducted on asymptomatic healthy subjects. Conclusion There is moderate evidence suggesting a sympatho-excitatory effect of joint mobilisation. Systematic Review Registration Number PROSPERO CRD42018089991.

Objectives To report a severe case of e-cigarette or vaping product use-associated lung injury with complex course requiring venovenous extracorporeal membrane oxygenation. Design Case report. Setting PICU in an academic medical center. Patients A 16-year-old girl presenting with gastrointestinal and respiratory symptoms was admitted to our PICU after having progressive respiratory failure and bilateral pulmonary ground-glass opacities on chest CT. Interventions Venovenous extracorporeal membrane oxygenation MEASUREMENTS AND MAIN RESULTS:: After extensive infectious workup was unrevealing, she reported a history of vaping e-cigarette containing either nicotine or delta-9-tetrahydrocannabinol oil prior to symptom onset. She was given a presumptive diagnosis of e-cigarette or vaping product use-associated lung injury. The PICU team in consultation with pulmonology and medical toxicology started high-dose IV methylprednisolone 1 mg/kg bid. Despite initial improvements, she continued to require positive pressure ventilation and developed pneumomediastinum with progression to tension pneumothoraces and a persistent air leak. Unable to maintain her oxygenation, she was placed on venovenous extracorporeal membrane oxygenation for a prolonged course and had a tracheostomy placement. The clinical course, severity, and range of interventions in affected patients around the country have varied widely. Respiratory symptoms have been the most severe, but the constellation of symptoms in e-cigarette or vaping product use-associated lung injury include constitutional symptoms (fevers, weight-loss) and gastrointestinal symptoms (nausea, vomiting, diarrhea). In many cases, steroid use led to rapid clinical improvements. However, other cases with severe illness, like our patient, necessitated high-dose IV steroids, intubation, and venovenous extracorporeal membrane oxygenation. The underlying etiology and pathophysiology of e-cigarette or vaping product use-associated lung injury remains unknown. The Centers for Disease Control and Prevention in conjunction with state/local health departments and the Food and Drug Administration is actively investigating the outbreak. Conclusions Clinicians need to be aware of the current outbreak of e-cigarette or vaping product use-associated lung injury and ask about vaping in patients presenting with gastrointestinal and respiratory symptoms. Treatment options are anecdotal and necessitate a multidisciplinary approach.

Distal renal tubular acidosis is a rare renal tubular disorder characterized by hyperchloremic metabolic acidosis and impaired urinary acidification. Mutations in three genes (ATP6V0A4, ATP6V1B1 and SLC4A1) constitute a monogenic causation in 58-70% of familial cases of distal renal tubular acidosis. Recently, mutations in FOXI1 have been identified as an additional cause. Therefore, we hypothesized that further monogenic causes of distal renal tubular acidosis remain to be discovered. Panel sequencing and/or whole exome sequencing was performed in a cohort of 17 families with 19 affected individuals with pediatric onset distal renal tubular acidosis. A causative mutation was detected in one of the three "classical" known distal renal tubular acidosis genes in 10 of 17 families. The seven unsolved families were then subjected to candidate whole exome sequencing analysis. Potential disease causing mutations in three genes were detected: ATP6V1C2, which encodes another kidney specific subunit of the V-type proton ATPase (1 family); WDR72 (2 families), previously implicated in V-ATPase trafficking in cells; and SLC4A2 (1 family), a paralog of the known distal renal tubular acidosis gene SLC4A1. Two of these mutations were assessed for deleteriousness through functional studies. Yeast growth assays for ATP6V1C2 revealed loss-of-function for the patient mutation, strongly supporting ATP6V1C2 as a novel distal renal tubular acidosis gene. Thus, we provided a molecular diagnosis in a known distal renal tubular acidosis gene in 10 of 17 families (59%) with this disease, identified mutations in ATP6V1C2 as a novel human candidate gene, and provided further evidence for phenotypic expansion in WDR72 mutations from amelogenesis imperfecta to distal renal tubular acidosis.

The rise of multi- and extensively drug-resistant Mycobacterium tuberculosis (M. tb) strains and co-infection with human immunodeficiency virus has escalated the need for new anti-M. tb drugs. Numerous challenges associated with the M. tb, in particular slow growth and pathogenicity level 3, discouraged use of this organism in past primary screening efforts. From current knowledge of the physiology and drug susceptibility of mycobacteria in general and M. tb specifically, it can be assumed that many potentially useful drug leads were missed by failing to screen directly against this pathogen. This review discusses recent high-throughput phenotypic screening strategies for anti-M. tb drug discovery. Emphasis is placed on prioritization of hits, including their extensive biological and chemical profiling, as well as the development status of promising drug candidates discovered with phenotypic screening.

Ensuring identity, purity, and reproducibility are equally essential during synthetic chemistry, drug discovery, and for pharmaceutical product safety. Many peptidic APIs are large molecules that require considerable effort for integrity assurance. This study builds on quantum mechanical 1H iterative Full Spin Analysis (HiFSA) to establish NMR peptide sequencing methodology that overcomes the intrinsic limitations of principal compendial methods in identifying small structural changes or minor impurities that affect effectiveness and safety. HiFSA sequencing yields definitive identity and purity information concurrently, allowing for API quality assurance and control (QA/QC). Achieving full peptide analysis via NMR building blocks, the process lends itself to both research and commercial applications as 1D 1H NMR (HNMR) is the most sensitive and basic NMR experiment. The generated HiFSA profiles are independent of instrument or software tools and work at any magnetic field strength. Pairing with absolute ...

Objective To examine the effects of dry needling against trigger point (TrP) injections (wet needling) applied to TrPs associated with neck pain. Methods Electronic databases were searched for randomized clinical trials in which dry needling was compared with TrP injections (wet needling) applied to neck muscles and in which outcomes on pain or pain-related disability were collected. Secondary outcomes consisted of pressure pain thresholds, cervical mobility, and psychological factors. The Cochrane Risk of Bias tool, the Physiotherapy Evidence Database score, and the Grading of Recommendations Assessment, Development, and Evaluation approach were used. Results Six trials were included. TrP injection reduced pain intensity (mean difference [MD ] –2.13, 95% confidence interval [CI] –3.22 to –1.03) with a large effect size (standardized mean difference [SMD] –1.46, 95% CI –2.27 to –0.65) as compared with dry needling. No differences between TrP injection and dry needling were found for pain-related disability (MD 0.9, 95% CI –3.09 to 4.89), pressure pain thresholds (MD 25.78 kPa, 95% CI –6.43 to 57.99 kPa), cervical lateral-flexion (MD 2.02°, 95% CI –0.19° to 4.24°), or depression (SMD –0.22, 95% CI –0.85 to 0.41). The risk of bias was low, but the heterogenicity and imprecision of results downgraded the evidence level. Conclusion Low evidence suggests a superior effect of TrP injection (wet needling) for decreasing pain of cervical muscle TrPs in the short term as compared with dry needling. No significant effects on other outcomes (very low-quality evidence) were observed. Level of Evidence Therapy, level 1a.

Background. Many centers accept a minimum body weight of 10 kg as threshold for kidney transplantation (Tx) in children. As solid evidence for clinical outcomes in multinational studies is lacking, we evaluated practices and outcomes in European children weighing below 10 kg at Tx. Methods. Data were obtained from the European Society of Paediatric Nephrology/European Renal Association and European Dialysis and Transplant Association Registry on all children who started kidney replacement therapy at

Background RGT is a major cause for early graft loss after KTx. Although evidence-based recommendations are lacking, aP is often used to prevent RGT. This systematic review aimed to determine the effectiveness and safety of aP in adult and pediatric KTx recipients. Methods MEDLINE, EMBASE, Cochrane Controlled Trials Register, conference proceedings, and electronic databases for trial registries were searched for eligible studies using search terms relevant to this review (April 21, 2020). The systematic review was carried out following the recommendations of the Cochrane Collaboration and the Prefered Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Results Twelve studies comprising 2370 patients (adult = 1415, pediatric = 955) were included, of which three were RCTs. The overall risk for developing RGT was lower in the group with aP compared with the control group (RR 0.24, 95% confidence interval 0.12-0.49). The antithrombotic drugs used were heparin (7/12), acetylsalicylic acid (2/12), a combination of both (2/12), and dipyridamole (1/12) with a high variability in timing, dosing, and mode of application. Adverse effects were reported rarely, with minor bleeding as the main complication. The non-randomized studies had significant risks of bias in the domains of patient selection, confounder, and measurement of outcomes. Conclusion Based on pooled analysis, aP seems to reduce the risk of RGT in KTx. However, the reliability of these results is limited, as the quality of the available studies is poor and information on adverse effects associated with aP is scarce. Additional high-quality research is urgently needed to provide sufficient data supporting the use of aP in KTx.

Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge management, analysis and interpretation of data in natural products research. Currently, reliance on a disparate set of non-standardized, insular, and specialized databases presents a series of challenges for data access, both within the discipline and for integration and interoperability between related fields. The fundamental elements of exchange are referenced structure-organism pairs that establish relationships between distinct molecular structures and the living organisms from which they were identified. Consolidating and sharing such information via an open platform has strong transformative potential for natural products research and beyond. This is the ultimate goal of the newly established LOTUS initiative, which has now completed the first steps toward the harmonization, curation, validation and open dissemination of 750,000+ referenced structure-organism pairs. LOTUS data is hosted on Wikidata and regularly mirrored on https://lotus.naturalproducts.net. Data sharing within the Wikidata framework broadens data access and interoperability, opening new possibilities for community curation and evolving publication models. Furthermore, embedding LOTUS data into the vast Wikidata knowledge graph will facilitate new biological and chemical insights. The LOTUS initiative represents an important advancement in the design and deployment of a comprehensive and collaborative natural products knowledge base.

The article “Swiss consensus recommendations on urinary tract infections in children”

Objective. To evaluate the effects of combining dry needling with other physical therapy interventions versus the application of the other interventions or dry needling alone applied over trigger points (TrPs) associated to neck pain. Databases and Data Treatment. Electronic databases were searched for randomized controlled trials where at least one group received dry needling combined with other interventions for TrPs associated with neck pain. Outcomes included pain intensity, pain-related disability, pressure pain thresholds, and cervical range of motion. The risk of bias (RoB) was assessed using the Cochrane risk of bias tool, methodological quality was assessed with PEDro score, and the quality of evidence was assessed by using the GRADE approach. Between-groups mean differences (MD) and standardized mean difference (SMD) were calculated. Results. Eight trials were included. Dry needling combined with other interventions reduced pain intensity at short-term (SMD −1.46, 95% CI −2.25 to −0.67) and midterm (SMD −0.38, 95% CI −0.74 to −0.03) but not immediately after or at long-term compared with the other interventions alone. A small effect on pain-related disability was observed at short-term (SMD −0.45, 95% CI −0.87 to −0.03) but not at midterm or long-term. The inclusion of dry needling was also effective for improving pressure pain thresholds only at short-term (MD 112.02 kPa, 95% CI 27.99 to 196.06). No significant effects on cervical range of motion or pain catastrophism were observed. Conclusion. Low-to-moderate evidence suggests a positive effect to the combination of dry needling with other interventions for improving pain intensity, pain-related disability, pressure pain thresholds, and cervical range of motion in people with neck pain associated with TrPs at short-term. No midterm or long-term effects were observed.

BACKGROUND Recognition of viral nucleic acids is one of the primary triggers for a type I interferon-mediated antiviral immune response. Inborn errors of type I interferon immunity can be associated with increased inflammation and/or increased susceptibility to viral infections as a result of dysbalanced interferon production. NFX1-type zinc finger-containing 1 (ZNFX1) is an interferon-stimulated double-stranded RNA sensor that restricts the replication of RNA viruses in mice. The role of ZNFX1 in the human immune response is not known. OBJECTIVE We studied 15 patients from 8 families with an autosomal recessive immunodeficiency characterized by severe infections by both RNA and DNA viruses and virally triggered inflammatory episodes with hemophagocytic lymphohistiocytosis-like disease, early-onset seizures, and renal and lung disease. METHODS Whole exome sequencing was performed on 13 patients from 8 families. We investigated the transcriptome, posttranscriptional regulation of interferon-stimulated genes (ISGs) and predisposition to viral infections in primary cells from patients and controls stimulated with synthetic double-stranded nucleic acids. RESULTS Deleterious homozygous and compound heterozygous ZNFX1 variants were identified in all 13 patients. Stimulation of patient-derived primary cells with synthetic double-stranded nucleic acids was associated with a deregulated pattern of expression of ISGs and alterations in the half-life of the mRNA of ISGs and also associated with poorer clearance of viral infections by monocytes. CONCLUSION ZNFX1 is an important regulator of the response to double-stranded nucleic acids stimuli following viral infections. ZNFX1 deficiency predisposes to severe viral infections and a multisystem inflammatory disease.

Objective The purpose of this study was to evaluate the effects of trigger point (TrP) dry needling alone or as an adjunct to other interventions on pain intensity and related disability in nontraumatic shoulder pain. Methods Ten databases were searched from inception to January 2020 for randomized clinical trials in which at least 1 group received TrP dry needling for shoulder pain of musculoskeletal origin with outcomes collected on pain intensity and related disability. Data extraction including participant and therapist details, interventions, blinding strategy, blinding assessment outcomes, and results were extracted by 2 reviewers. The risk of bias (Cochrane Risk of Bias, Cochrane Guidelines), methodological quality (Physiotherapy Evidence Database score), and evidence level (Grading of Recommendations Assessment, Development, and Evaluation approach) were assessed. The search identified 551 publications with 6 trials eligible for inclusion. Results There was moderate-quality evidence that TrP dry needling reduces shoulder pain intensity with a small effect (mean difference = −0.49 points, 95% CI = −0.84 to −0.13; standardized mean difference = −0.25, 95% CI = −0.42 to −0.09) and low-quality evidence that TrP dry needling improves related disability with a large effect (mean difference = −9.99 points, 95% CI −15.97 to −4.01; standardized mean difference = −1.14, 95% CI −1.81 to −0.47) compared with a comparison group. The effects on pain were only found at short term. The Cochrane Risk of Bias was generally low, but the heterogenicity of the results downgraded the evidence level. Conclusion Moderate- to low-quality evidence suggests positive effects of TrP dry needling for pain intensity (small effect) and pain-related disability (large effect) in nontraumatic shoulder pain of musculoskeletal origin, mostly at short term. Future clinical trials investigating long-term effects are needed. Impact Dry needling is commonly used for the management of musculoskeletal pain. This is the first meta-analysis to examine the effects of dry needling on nontraumatic shoulder pain.

Objective: The aim of this study was to evaluate the effect of acupuncture/electroacupuncture, alone or combined with other interventions, on pain intensity, pain-related disability, and strength in lateral epicondylalgia (LE) of musculoskeletal origin. Databases and data treatment: Electronic databases were searched for randomized clinical trials, where at least one group received acupuncture or electroacupuncture for LE of musculoskeletal origin. To be eligible, trials had to include humans and collect outcomes on pain intensity or pain-related disability in LE. Data were extracted by two reviewers. The risk of bias (RoB) of the trials was assessed using the Cochrane RoB tool, methodological quality was assessed with the Physiotherapy Evidence Database (PEDro) score, and the level of evidence was summarized using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Standardized mean differences (SMDs) using random effects were calculated. Results: A total of 14 trials (10 acupuncture) were included. The meta-analysis found a moderate effect size of acupuncture (SMD = −0.66, 95% confidence interval (CI) = −1.22 to −0.10), but not electroacupuncture (SMD = −0.08, 95% CI = −0.99 to 0.83), in the reduction of elbow pain as compared to a comparative group. Acupuncture exhibited a significant moderate effect size (SMD = −0.51, 95% CI = −0.91 to −0.11) in the improvement of related-disability. Acupuncture (SMD = 0.36, 95% CI = 0.16 to 0.57), but not electroacupuncture (SMD = 0.34, 95% CI = −0.29 to 0.98), exhibited a significant but small effect size on strength. Most significant effects were in the short term. The RoB was low but the heterogeneity of trial results led to a downgrading of the GRADE evidence level. Conclusion: Low-level evidence suggests positive effects of acupuncture, but not electroacupuncture, for pain, related-disability, and strength, in LE of musculoskeletal origin, in the short term.

Objective To describe the clinical characteristics, treatment, and outcomes of a multinational cohort of patients with macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). Study design International pediatric rheumatologists were asked to collect retrospectively the data of patients with the co-occurrence of MAS and TMA. Clinical and laboratory features of patients with systemic juvenile idiopathic arthritis (sJIA)-associated MAS and TMA were compared with those of an historical cohort of patients with sJIA and MAS. Results Twenty-three patients with MAS and TMA were enrolled: 17 had sJIA, 2 systemic lupus erythematosus, 1 juvenile dermatomyositis, 1 mixed connective tissue disease, and 2 undifferentiated connective tissue disease. Compared with the historical cohort of MAS, patients with sJIA with coexistent MAS and TMA had higher frequencies of renal failure and neurologic involvement, hemorrhage, jaundice, and respiratory symptoms, as well as more severe anemia and thrombocytopenia, higher levels of alanine aminotransferase, lactate dehydrogenase, bilirubin and D-dimer, and lower levels of albumin and fibrinogen. They also required admission to the intensive care unit more frequently. Among patients tested, complement abnormalities and reduced ADAMTS13 activity were observed in 64.3% and 44.4% of cases, respectively. All patients received glucocorticoids. Treatment for TMA included plasma-exchange, eculizumab, and rituximab. Conclusions The possible coexistence of MAS and TMA in rheumatic diseases may be underrecognized. This association should be considered in patients with MAS who develop disproportionate anemia, thrombocytopenia, and lactate dehydrogenase increase, or have multiorgan failure.

Background and objective To evaluate the effects of percutaneous electrical stimulation (PENS) alone or as an adjunct with other interventions on pain and related disability in musculoskeletal pain conditions. Databases and data treatment Search of MEDLINE, EMBASE, AMED, CINAHL, EBSCO, PubMed, PEDro, Cochrane Library, SCOPUS and Web of Science databases. Randomized controlled trials where at least one group received any form of PENS for musculoskeletal condition. Studies had to include humans and collect outcomes on pain and related disability in musculoskeletal pain. Risk of bias was assessed by the Cochrane Guidelines, the quality of evidence by using the GRADE approach. Standardized mean differences (SMD) were calculated. Results Sixteen studies were included and included heterogeneous musculoskeletal conditions with short- or midterm follow-ups. PENS alone had a large effect (SMD -1.22, 95% CI -1.66 to -0.79) on pain and a small effect (SMD -0.33, 95% CI -0.61 to -0.06) on related disability at short-term as compared with sham. A moderate effect of PENS alone (SMD -0.71, 95% CI -1.23 to -0.19) on pain when compared with other interventions was observed. The inclusion of PENS with other interventions had a moderate effect for decreasing pain at short- (SMD -0.70, 95% CI -1.02 to -0.37) and midterm (SMD -0.68, 95% CI -1.10 to -0.27). No effect at midterm (SMD -0.21, 95% CI -0.52 to 0.10) on related disability was seen. The risk of bias was generally low; but the heterogenicity of the results downgraded the level of evidence. Conclusion There is low level of evidence suggesting the effects of PENS alone or in combination for pain, but not related disability, in musculoskeletal pain. Level of evidence Therapy, level 1a. Registration number: CRD42019131331. Significance This meta-analysis investigating the effectiveness of PENS for the management of pain and related disability in musculoskeletal pain conditions found that PENS could decrease level of pain intensity but not relateddisability in musculoskeletal pain disorders.

ObjectiveTo evaluate the effects of ultrasound-guided percutaneous electrolysis alone or as an adjunct to other interventions on pain and pain-related disability for musculoskeletal pain conditions.Databases and Data TreatmentSearch of MEDLINE database, Allied and Complementary Medicine Database, EMBASE database, Cumulative Index to Nursing & Allied Health Literature database, EBSCO database, PubMed database, Physiotherapy Evidence Database, Cochrane Library database, Scopus database, and Web of Science database. Randomized controlled trials in which at least one group received ultrasound-guided percutaneous electrolysis for treatment of musculoskeletal pain. To be eligible, studies had to include humans and collect outcomes on pain intensity and pain-related disability for musculoskeletal pain syndromes. Data were extracted by two reviewers. The risk of bias was assessed by the Cochrane Guidelines and the quality of evidence was reported using the Grading of Recommendations Assessment, Development and Evaluation approach. Standardized mean differences (SMDs) and random effects were calculated.ResultsTen studies were included. The meta-analysis found that ultrasound-guided percutaneous electrolysis reduced the mean pain intensity by –2.06 (95% confidence interval [CI], –2.69 to –1.42) and the pain intensity as assessed with a visual analog scale or a numeric pain rating scale with a large size effect (SMD = –1.15; 95% CI, –1.48 to –0.81) and also improved pain-related disability with a large size effect (SMD = 0.95; 95% CI, 0.73–1.18) as compared with comparison groups. No differences in effect sizes were found among the short-term, midterm, and long-term follow-ups. The risk of bias was generally low, but the heterogeneity of the overall result downgraded the evidence level. Trials included heterogeneous musculoskeletal pain conditions and short-term, midterm, and long-term follow-ups.ConclusionModerate evidence suggests positive effects of ultrasound-guided percutaneous electrolysis for pain and pain-related disability in musculoskeletal pain conditions relative to a comparison group in the short term, midterm, and long term.

BACKGROUND Renal replacement therapy for paediatric end-stage renal disease (ESRD) has developed steadily since its introduction five decades ago. Continuous and long-term analysis of patient outcomes is essential for quality control. METHODS The Swiss Paediatric Renal Registry, founded in 1970, includes patients diagnosed with ESRD, defined as dialysis for more than three months or renal transplantation, at age

Botanical dietary supplements produced from hops (Humulus lupulus) containing the chemopreventive compound xanthohumol and phytoestrogen 8-prenylnaringenin are used by women to manage menopausal symptoms. Due to the long half-lives of prenylated hop phenols and reports that they inhibit certain cytochrome P450 enzymes, a botanically authenticated and chemically standardized hop extract was tested for Phase I pharmacokinetic drug interactions. Sixteen peri- and post-menopausal women consumed the hop extract twice daily for 2 weeks, and the pharmacokinetics of tolbutamide, caffeine, dextromethorphan, and alprazolam were evaluated before and after supplementation as probe substrates for the enzymes CYP2C9, CYP1A2, CYP2D6, and CYP3A4/5, respectively. The observed area under the time-concentration curves were unaffected, except for alprazolam which decreased 7.6% (564.6 ± 46.1 h*μg/L pre-hop and 521.9 ± 36.1 h*μg/L post-hop; p-value 0.047), suggesting minor induction of CYP3A4/5. No enzyme inhibition was detected. According to FDA guidelines, this hop dietary supplement caused no clinically relevant pharmacokinetic interactions with respect to CYP2C9, CYP1A2 , CYP2D6, or CYP3A4/5. Serum obtained after consumption of the hop extract was analyzed using UHPLC-MS/MS to confirm compliance. Abundant Phase II conjugates of the hop prenylated phenols were observed including monoglucuronides and monosulfates as well as previously unreported diglucuronides and sulfate-glucuronic acid diconjugates.

Electronic cigarettes (e-cigarettes) are battery-operated devices to insufflate nicotine or other psychoactive e-liquid aerosols. Despite initial claims of e-cigarettes as a nicotine-cessation device, aggressive marketing of e-cigarettes has led to an explosion in adolescents’ and young adults’ use over the last few years. Coupled with a lack of adequate investigation and regulation of e-cigarettes, the USA is facing an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) starting in mid-2019. While little long-term health hazard data are available, the components and constituents of e-cigarettes may adversely impact health. Propylene glycol and glycerin are humectants (water-retaining excipients) that generate pulmonary irritants and carcinogenic carbonyl compounds (e.g., formaldehyde, acetaldehyde, and acrolein) when heated in e-cigarettes. Metals contained in heating coils and cartridge casings may leach metals such as aluminum, chromium, iron, lead, manganese, nickel, and tin. Flavoring agents are considered safe for ingestion but lack safety data for inhalational exposures. Diacetyl, a common buttery flavoring agent, has known pulmonary toxicity with inhalational exposures leading to bronchiolitis obliterans. In 2019, clusters of lung injury associated with e-cigarette use were identified in Wisconsin and Illinois. Patients with EVALI present with a constellation of respiratory, gastrointestinal, and constitutional symptoms. Radiographically, patients have bilateral ground glass opacifications. As of February 18, 2020, the Centers for Disease Control has identified 2807 hospitalized patients diagnosed with either “confirmed” or “probable” EVALI in the US. Currently, vitamin E acetate (VEA) used as a diluent in tetrahydrocannabinol vape cartridges is implicated in EVALI. VEA cuts tetrahydrocannabinol oil without changing the appearance or viscosity. When inhaled, pulmonary tissue lacks the mechanism to metabolize and absorb VEA, which may lead to its accumulation. While most EVALI patients were hospitalized, treatment remains largely supportive, and use of corticosteroids has been associated with clinical improvement. The outbreak of EVALI highlights the need for regulation of e-cigarette devices and e-liquids. Clinicians need to be aware of the health hazards of e-cigarettes and be vigilant in asking about vaping.

This article reviews and develops a perspective for the meaning of authenticity in the context of quality assessment of botanical materials and the challenges associated with discerning adulterations vs. contaminations vs. impurities. Authentic botanicals are by definition non-adulterated, a mutually exclusive relationship that is confirmed through the application of a multilayered set of analytical methods designed to validate the (chemo) taxonomic identity of a botanical and certify that it is devoid of any adulteration. In practice, the ever-increasing sophistication in the process of intentional adulteration, as well as the growing number of botanicals entering the market, altogether necessitate a constant adaptation and reinforcement of authentication methods with new approaches, especially new technologies. This article summarizes the set of analytical methods - classical and contemporary – that can be employed in the authentication of botanicals. Particular emphasis is placed on the application of untargeted metabolomics and chemometrics. An NMR-based untargeted metabolomic model is proposed as a rapid, systematic, and complementary screening for the discrimination of authentic vs. potentially adulterated botanicals. Such analytical model can help advance the evaluation of botanical integrity in natural product research.

There has been a significant demand for the development and improvement of technology used for the detection and identification of Chemical Warfare Agents (CWAs). Some of the current detection technology being used by the U.S. government includes multipass gas cell coupled Fourier Transform Infrared (FTIR) spectroscopy and Lightweight Chemical Detectors (LCD) systems. While these systems possess adequate sensitivity to detect CWAs in general, their analysis times are not considered 'rapid' nor are they able to identify the specific CWA. The U.S. Army Dugway Proving Ground's annual S/K Challenge event provides the opportunity to assess the performance and reliability of prospective detection instrumentation being developed by researchers worldwide to optimize their performance. To do so, trial testing of CWA simulants in both indoor and outdoor environments was performed, mimicking past attack scenarios. Membrane Inlet Mass Spectrometric (MIMS) technology on a portable system was successful in performing a rapid analysis along with identification of each CWA simulant utilized during the trials. The MIMS system can detect and quantify low-mass permeable compounds with parts-per-trillion limits of detection. This allows for analysis to be achieved within seconds after the initial exposure time, which is significantly faster than the FTIR and LCD systems currently used.

SUMMARY Secondary caries at the tooth-resin interface is the primary reason for replacement of resin composite restorations. The tooth-resin interface is formed by the interlocking of resin material with hydroxyapatite crystals in enamel and collagen mesh structure in dentin. Efforts to strengthen the tooth-resin interface have identified chemical agents with dentin collagen cross-linking potential and antimicrobial activities. The purpose of the present study was to assess protective effects of bioactive primer against secondary caries development around enamel and dentin margins of class V restorations, using an in vitro bacterial caries model. Class V composite restorations were prepared on 60 bovine teeth (n=15) with pretreatment of the cavity walls with control buffer solution, an enriched fraction of grape seed extract (e-GSE), 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide/N-hydroxysuccinimide, or chlorhexidine digluconate. After incubating specimens in a bacterial model with Streptococcus mutans for four days, dentin and enamel were assessed by fluorescence microscopy. Results revealed that only the naturally occurring product, e-GSE, significantly inhibited the development of secondary caries immediately adjacent to the dentin-resin interface, as indicated by the caries inhibition zone. No inhibitory effects were observed in enamel margins. The results suggest that the incorporation of e-GSE into components of the adhesive system may inhibit secondary caries and potentially contribute to the protection of highly vulnerable dentin-resin margins.

Objective Chronic ankle instability (CAI) is reported after ankle sprain. Our aim was to assess differences in mechanical pain sensitivity of lower extremity nerve trunks and physical performance between amateur soccer players with and without CAI. Design A cross-sectional case-control study. Setting Amateur soccer teams. Participants Fifty-five male soccer players, 28 with and 27 without CAI participated. Main outcome measures The perceived instability was assessed with the Cumberland Ankle Instability Tool (CAIT). Pressure pain thresholds (PPTs) on the common peroneal and tibialis nerve trunks, vertical jump, lateral step-down test and joint position sense of the knee were assessed by a blinded assessor. Results Soccer players with CAI showed lower PPTs over the common peroneal nerve than those without CAI (between-groups mean difference: 1.0 ± 0.8 kg/cm2, P 0.310]) were found. PPT over the common peroneal nerve exhibited a significant moderate correlation with the CAIT score (r = 0.528, P Conclusion Amateur soccer players with CAI have higher pressure pain sensitivity over the common peroneal nerve but exhibit similar physical performance to amateur soccer players without CAI.

Background Older age at organ transplantation is associated with increased risk of infection and malignancy but reduced risk of cellular rejection. De novo donor-specific anti-HLA antibodies (dnDSA), are key biomarkers associated with reduced long-term allograft survival, yet there is a lack of data focusing on age-associated changes. Methods Development of dnDSA was restrospectively analyzed in all subjects who received a kidney transplant at the University Hospital Zurich between 01/2006 and 02/2015. Follow up continued until 03/2016. The incidence of dnDSA in different age categories was compared with special focus on the extremes of age: children

In children after haemolytic-uraemic syndrome (HUS), little is known about long-term health-related quality of life (HRQoL) and psychological adjustment as defined by behavioural problems, depressive symptoms and post-traumatic stress symptoms. Sixty-two paediatric patients with a history of HUS were included in this study. Medical data of the acute HUS episode were retrieved retrospectively from hospital records. Data on the clinical course at study investigation were assessed by clinical examination and laboratory evaluation. HRQoL and psychological adjustment data were measured by standardised, parent- and self-reported questionnaires. Haemolytic-uraemic syndrome was diagnosed at a mean of 6.5 years before the initiation of the study (standard deviation 2.9, range 0.1–15.7) years. Among the preschool children, parents reported that their child was less lively and energetic (HRQoL emotional dimension), while no increased behavioural problems were reported. In the school-age children, self- and proxy-reported HRQoL was well within or even above the norms, while increased total behavioural problems were found. The school-age children reported no increased depression scores. Also none of the children met the criteria for full or partial HUS-associated posttraumatic stress disorder. Healthcare providers should be particularly alert to behavioural problems in school-age children with a history of HUS and to lower HRQoL in preschool children.

We present an analysis of ambient benzene, toluene, and xylene isomers in the Eagle Ford shale region of southern Texas. In situ air quality measurements using membrane inlet mobile mass spectrometry revealed ambient benzene and toluene concentrations as high as 1000 and 5000 parts-per-billion, respectively, originating from specific sub-processes on unconventional oil and gas well pad sites. The detection of highly variant contamination events attributable to natural gas flaring units, condensate tanks, compressor units, and hydrogen sulfide scavengers indicates that mechanical inefficiencies, and not necessarily the inherent nature of the extraction process as a whole, result in the release of these compounds into the environment. This awareness of ongoing contamination events contributes to an enhanced knowledge of ambient volatile organic compounds on a regional scale. While these reconnaissance measurements on their own do not fully characterize the fluctuations of ambient BTEX concentrations that likely exist in the atmosphere of the Eagle Ford Shale region, they do suggest that contamination events from unconventional oil and gas development can be monitored, controlled, and reduced.

Additive manufacturing (AM) methods of 3D printing are increasingly opening up new paths in medical technology. Alex Berry, founder of Sutrue (cf. Interview, p. 20), and Richard Trimlett, consultant at the Royal Brompton Hospital, are focusing strategically on AM for applications in cardiology. Is it possible to improve the “golden hands” of an experienced heart surgeon? Yes, it is. Using the example of a machine for performing sutures during operations and a cardiac stabilizer for endoscopic heart operations, Sutrue shows how operations on the heart can be performed more safely. Heart operations are soon to become faster and safer. And there is even more good news: patients are recovering faster.

Background: To evaluate the effect of trigger point dry needling alone or as an adjunct with other interventions on pain and related disability in people with knee pain. Methods: Several electronic databases were searched for randomized controlled trials where at least one group received dry needling for knee pain. Studies had to include human subjects and collect outcomes on pain and pain-related disability in musculoskeletal knee pain. Data were extracted by two reviewers. The risk of bias was assessed by the Cochrane Guidelines, methodological quality was assessed with the Physiotherapy Evidence Database (PEDro) score, and the quality of evidence by using the GRADE approach. Standardized mean differences (SMD) were calculated. Results: Ten studies (six patellofemoral pain, two knee osteoarthritis, two post-surgery knee pain) were included. The meta-analysis found moderate effect sizes of dry needling for reducing pain (SMD −0.53, 95% CI −0.87 to −0.19) and improving related disability (SMD −0.58, 95% CI −1.08 to −0.09) as compared to a comparison group at short-term. The main effect was observed for patellofemoral pain (SMD −0.64, 95% CI −1.17 to −0.11). No significant effects were observed at mid- or long-term follow-ups. The risk of bias was generally low, but the heterogenicity and the imprecision of the results downgraded the level of evidence. Conclusion: Low to moderate evidence suggests a positive effect of trigger point dry needling on pain and related disability in patellofemoral pain, but not knee osteoarthritis or post-surgery knee pain, at short-term. More high-quality trials investigating long-term effects are clearly needed.

Therapies originating from traditional medical systems are widely used by patients in both India and the United States. The first India-US Workshop on Traditional Medicine was held in New Delhi, India, on March 3 and 4, 2016, as a collaboration between the Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH) of the Government of India, the US National Cancer Institute (NCI), National Institutes of Health, and the Office of Global Affairs, US Department of Health and Human Services. It was attended by Indian and US policymakers, scientists, academics, and medical practitioners from various disciplines. The workshop provided an opportunity to open a dialogue between AYUSH and NCI to identify promising research results and potential topics for Indo-US collaboration. Recommendations that emerged from the workshop underlined the importance of applying rational and scientific approaches for drug development; standardizing traditional medicine products and procedures to ensure reliability and reproducibility; promotion of collaboration between Indian traditional medicine practitioners and researchers and US researchers; greater integration of evidence-based traditional medicine practices with mainstream medical practices in India; and development of training programs between AYUSH and NCI to facilitate crosstraining. Several positive developments took place after the thought-provoking deliberations.

Clinical gout has rarely been described after pediatric renal transplantation (RTx), although asymptomatic hyperuricemia is common in these patients. We describe three male pediatric patients who presented with gouty arthritis 7-8.5 years following RTx. Since receiving allopurinol, all patients had been free of gouty symptoms. To prevent severe bone marrow depletion, the dosage of azathioprine, an immunosupressant drug, was reduced by 50% to prevent interaction with allopurinol. Because atypical presentation of gout can occur, a high index of suspicion is needed to allow appropriate diagnosis of this disease in patients with skeletal pain after RTx.

Infants with a body weight of less than 10 kg are often not considered to be suitable candidates for renal transplantation (RTx). The objective of this study was to evaluate this arbitrary weight threshold for pediatric RTx. We conducted a multicenter, retrospective, match-controlled cohort study on infants weighing less than 10 kg at time of engrafting (low-weight group [LWG], n = 38) compared to a matched control group (n = 76) with a body weight of 10–15 kg, using data from the first 2 years post-transplant derived from the CERTAIN Registry. Patient survival was 97 and 100% in the LWG and control groups, respectively (P = 0.33), and death-censored graft survival was 100 and 95% in the LWG and control groups, respectively (P = 0.30). Estimated glomerular filtration rate at 2 years post-transplant was excellent and comparable between the groups (LWG 77.6 ± 34.9 mL/min/1.73 m2; control 74.8 ± 29.1 mL/min/1.73 m2; P = 0.68). The overall incidences of surgery-related complications (LWG 11%, control 23%; P = 0.12) and medical outcome measures (LWG 23%, control 36%, P = 0.17) were not significantly different between the groups. The medical outcome measures included transplant-related viral diseases (LWG 10%, control 21%; P = 0.20), acute rejection episodes (LWG 14%, control 29%; P = 0.092), malignancies (LWG 3%, control 0%; P = 0.33) and arterial hypertension (LWG 73%, control 67%; P = 0.57). These data suggest that RTx in low-weight children is a feasible option, at least in selected centers with appropriate surgical and medical expertise.

Background Proprioception and vertical jump are important parameters in the performance and prevention of injuries in futsal. However, very few studies have analyzed the role of multistation exercises to improve these variables. The purpose of this study was to assess the effects of a six-week multistation exercise program on knee joint position sense (JPS) and countermovement jump (CMJ) of futsal players. Methods Thirty-four male futsal players randomly classified into experimental (N.=17) or control group (N.=17). The experimental group included a multistation exercise protocol to their training routines (2 times/week - 6 weeks); the control group continued their training routines. All the players completed similar training routines outside of the multistation exercises. Before (baseline), just after the intervention (Post6Wk) and four weeks later (Post10Wk), CMJ and knee JPS (absolute, relative and variable angular error: AAE, RAE and VAE, respectively) were evaluated. Results ANOVA showed that the experimental group significantly decreased VAE at Post10Wk compared to baseline, suggestive of greater proprioceptive precision, while the control group significantly increased AAE, RAE and VAE at Post10Wk compared to baseline. The experimental group exhibited lower and thus, better AAE and VAE than the control group at Post10Wk, although no significant differences were found at Post6Wk. No significant differences was found in the CMJ. Conclusions A six weeks of multistation program may help improve proprioceptive precision of futsal players, even one month after finishing the 6-wk multistation training program. However, this is not long enough to improve proprioceptive acuity and maximum vertical jump. Therefore, the meaningful of these results in term of performance are unclear.

With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets., Covering: up to 2018 With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.

Der padiatrische Teil der S3-Leitlinie „Analgesie, Sedierung und Delirmanagement in der Intensivmedizin“ hat das Ziel, Kolleginnen und Kollegen, die in die Betreuung von Neugeborenen und Kindern auf Intensivstationen involviert sind, eine umfassende evidenz- und konsensus-basierte Handlungsgrundlage zu geben. Zugleich sollen Impulse fur weitere Forschungsaktivitaten gegeben werden. In der Uberarbeitung von 2015 werden klinisch relevanten Schlusselfragen entsprechend der aktuellen Studienlage aus pflegerischer und arztlicher Sicht neu beleuchtet.

Countercurrent separation (CCS) utilizes the differential partitioning behavior of analytes between two immiscible liquid phases. We introduce the first platform (“CherryOne”) capable of real-time monitoring, metering, and control of the dynamic liquid-liquid CCS process. Automated phase monitoring and volumetrics are made possible with an array of sensors, including the new permittivity-based Phase Metering Apparatus (PMA). Volumetric data for each liquid phase are converted into a dynamic real-time display of stationary phase retention (Sf) and eluent partition coefficients (K), which represent critical parameters of CCS reproducibility. When coupled with the elution-extrusion operational mode (EECCC), automated Sf and K determination empowers untargeted and targeted applications ranging from metabolomic analysis to preparative purifications.

Little is known about health-related quality of life (HRQoL) and mental health of parents having children with a history of hemolytic uremic syndrome (HUS). This study included 63 mothers and 58 fathers of a cohort of 63 HUS-affected children. At assessment, the mean time since a child experienced an acute episode of HUS was 6.4 years. Parental HRQoL, mental health and posttraumatic stress disorder (PTSD) were assessed with standardized self-report questionnaires. Medical data were extracted from patients’ hospital records. The HRQoL and mental health of both the mothers and fathers were not impaired compared to normative data. However, a shorter time since a child’s acute HUS episode was a significant predictor of lower HRQoL among the mothers, while no such effect was found among the fathers. Two fathers (3 %), but no mothers, met the criteria for a diagnosis of HUS-related full PTSD; one father (2 %) and four mothers (6 %) met the criteria for a diagnosis of HUS-related partial PTSD. Our study shows that most parents of our study sample were doing well in terms of HRQoL and mental health, although a small number met the criteria for full or partial PTSD diagnosis due to their child’s HUS. We therefore recommend that healthcare providers pay special attention to parents regarding PTSD symptoms during the clinical follow-up of a HUS-affected child since some parents may benefit from psychological support.

Ureteropelvic junction obstruction (UPJO) is the most common obstructive uropathy and its optimal management remains controversial. However, there is a current trend towards non-surgical management. We aimed to determine the effects of the non-surgical management in children with unilateral UPJO. For a systematic review, we searched MEDLINE, EMBASE, CENTRAL, clinical trials registries, and selected conference proceedings for eligible studies. Any type of study reporting the outcomes renal function, secondary surgical intervention, drainage pattern or hydronephrosis of non-surgical management in children with unilateral UPJO was included. Data from 20 studies were extracted and evaluated by two independent authors. The pooled prevalence was 21% for split renal function deterioration, 27.9% for secondary surgical intervention, 3.2% for progressive hydronephrosis, and 82.2% for improved drainage pattern. Not all patients with surgical intervention regained split renal function from enrolment. Renal imaging methods did not strongly correlate with each other. Many studies had to be excluded because of a lack of detection of an obstruction or mixed populations with bilateral UPJO or other uropathies. The variable definitions of UPJO, different criteria for surgical intervention, incongruity of management protocols, and the imprecise reporting of outcomes were limiting factors in the comparability of the results, leading to heterogeneity in meta-analyses. Although the available evidence cannot recommend or refute the current non-surgical management, the systematic review clarifies aspects of the ongoing controversy by providing realistic estimates for non-surgical management in children with unilateral UPJO. Additionally, it reveals unclear potential risks, particularly for long-term outcomes, which were rarely reported.

The objective of the study was the development of an abridged risk-stratified imaging algorithm for the management of children with unilateral ureteropelvic junction obstruction (UPJO). Data on timing, frequency and duration of diagnostic imaging in children with unilateral UPJO was extracted retrospectively. Based on these findings, an abridged imaging algorithm was developed without changing the intended management by the clinicians and the outcome of the individual patient. The potential reduction of imaging studies was analysed and stratified by risk and management groups. The reduction in imaging studies, seen for ultrasound (US) and functional imaging (FI), was 45% each. On average, this is equivalent to 3 US and 1 FI studies less for every patient within the study period. The change was more pronounced in the low-risk groups. Progression of UPJO never occurred after 2 years of age and all secondary surgeries were carried out until the age of 3.Although our findings need to be validated by further prospective research, the developed imaging algorithm represents a risk-stratified approach towards less imaging studies in children with unilateral UPJO, and a follow-up beyond 3 years of age should be considered only in selected cases at the discretion of the clinician. What is Known: • ultrasound and functional imaging represent an integral part of therapeutic decision-making in children with unilateral ureteropelvic junction obstruction • imaging studies cannot accurately assess which patients are in need of surgical intervention, therefore close, serial imaging is preferred What is New: • a new, risk-stratified imaging algorithm was developed for the first 3 years of life • applying this algorithm could lead to a considerable reduction of imaging studies, and also the associated risks and health-care costs.

A 7-year-old boy with autosomal recessive polycystic kidney disease underwent pre-emptive living-related kidney transplantation from his mother. Initial immunosuppression consisted of cyclosporin, mycophenolate mofetil (MMF), and prednisone. Ten weeks after transplantation he experienced steroid resistant rejection (Banff Grade II) and cyclosporin was switched to tacrolimus. Renal function subsequently normalized and plasma creatinine has been stable at between 60 and 78 mmolul for the following 3 years. No side effects to tacrolimus were noted at a dose of 10 mguday with subsequent whole blood trough levels between 7.3 and 11.0 mgul. MMF was administered at a dose of 800 muday (two-thirds of the recommended dose due to altered metabolism with concurrent tacrolimus treatment). Prednisone was given at a dose of 5 mg on alternate days. At the age of 10 years the patient developed a few lesions of molluscum contagiosum (MC) on the trunk. Over a period of a few weeks the number of lesions increased dramatically (Figure 1) and extended over the anterior and posterior trunk as well as the extremities, embarrassing the patient and his parents. Intensive local treatment was initiated: cryotherapy was tried for a short time, but was abandoned as lesions recurred immediately after treatment. Topical treatment with silver nitrate also failed (Figure 2). A slow reduction of tacrolimus dosage aiming at trough levels of 5 mgul was tried and cryotherapy was restarted. Again there was no improvement. In addition to MC, two episodes of communityacquired pneumonia occurred 3 and 6 months after MC had developed and were successfully treated with a 10-day course of oral amoxicillin. After the second pulmonary infection it was decided to discontinue MMF and start azathioprine at a dose of 1 mgukg while tacrolimus and prednisone dosage were not changed. FACS scan demonstrated normal lymphocyte subsets levels at this stage and serum immunoglobulin levels (IgG, IgA, and IgM) were normal. The effect was impressive: MC lesions decreased dramatically within 1 week after this second change of immunosuppression with continued cryotherapy. The skin lesions improved rapidly and disappeared after

Background Information on lipid abnormalities in end-stage renal disease (ESRD) mainly originates from adult patients and small paediatric studies. We describe the prevalence of dyslipidaemia, and potential determinants associated with lipid measures in a large cohort of paediatric ESRD patients. Methods In the ESPN/ERA-EDTA registry, lipid measurements were available for 976 patients aged 2-17 years from 19 different countries from the year 2000 onwards. Dyslipidaemia was defined as triglycerides >100 mg/dL (2-9 years) or >130 mg/dL (9-17 years), high-density lipoprotein (HDL) cholesterol 145 mg/dL. Missing data were supplemented using multiple imputation. Results The prevalence of dyslipidaemia was 85.1% in peritoneal dialysis (PD) patients, 76.1% in haemodialysis (HD) patients and 55.5% among renal allograft recipients. Both low and high body mass index (BMI) were associated with a less favourable lipid profile. Younger age was associated with a worse lipid profile among PD patients. HDL levels significantly improved after transplantation, whereas no significant improvements were found for triglyceride and non-HDL levels. In transplant recipients, use of cyclosporin was associated with significantly higher non-HDL and HDL levels than tacrolimus usage (P < 0.01). In transplant patients with eGFR < 29 mL/min/1.73 m2, the mean triglyceride level was 137 mg/dL (99% confidence interval (CI): 119-159) compared with 102 mg/dL among those with eGFR > 90 mL/min/1.73 m2 (P < 0.0001). Conclusions Dyslipidaemia is common among paediatric ESRD patients in Europe. Young age and PD treatment are associated with worse lipid profiles. Although lipid levels generally improve after transplantation, dyslipidaemia may persist due to decreased graft function, high BMI or to the use of certain immunosuppressants

Background. Laparoscopic living kidney nephrectomy is thought to be associated with reduced morbidity, when compared to open nephrectomy. The purpose of this study was to explore the impact of these techniques on donors’ clinical outcomes, satisfaction and motivation to donate. Methods. Clinical outcomes were retrospectively compared in 152 open (n ¼ 71) or laparoscopic (n ¼ 81) donor procedures. Donor satisfaction and motivation were assessed with a self-administered questionnaire. Results. The complication rate was the same with both procedures and the majority of complications were mild. Laparoscopy was significantly less painful and resulted in an insignificantly faster return to active life. More than 80% of the donors volunteered to donate without pressure. Worries about future health status, pain or scars were not important in the decision to donate. Similarly, only 15% considered the surgical procedure as instrumental for their decision. Few donors currently worried about their health with one kidney and more than 95% of the donors in both groups stated that they would give their kidney again. Conclusions. Living donor nephrectomy is safe, regardless of the procedure used. Although the laparoscopic nephrectomy offers clear short-term benefits over the open nephrectomy, donors’ satisfaction was excellent with both surgical approaches. Moreover, the type of procedure did not seem to influence their decision to donate.

Children often merit priority in access to deceased donor kidneys by organ-sharing organizations. We report the impact of the new Swiss Organ Allocation System (SOAS) introduced in 2007, offering all kidney allografts from deceased donors