Rationale and design of the RIACT–study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial

BACKGROUND: Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90%) of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab) improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation. METHODS/DESIGN: The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited. DISCUSSION: It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy. TRIAL REGISTRATION: Clinical trials gov. number: NCT0111766

A Robotic System for Solo Surgery in Flexible Ureterorenoscopy

Urolithiasis is a common disease with increasing prevalence across all ages. A common treatment option for smaller kidney stones is flexible ureterorenoscopy (fURS), where a flexible ureteroscope (FU) is used for stone removal and to inspect the renal collecting system. The handling of the flexible ureteroscope and end effectors (EEs), however, is challenging and requires two surgeons. In this article, we introduce a modular robotic system for endoscope manipulation, which enables solo surgery (SSU) and is adaptable to various hand-held FUs. Both the developed hardware components and the proposed workflow and its representation in software are described. We then present and discuss the results of an initial user study. Finally, we describe subsequent developmental steps towards more extensive testing by clinical staff

Исследование эффективности брейкеров для жидкостей гидроразрыва пласта

Исследование влияния биоразлагаемых брейкеров на реологические характеристики жидкостей гидроразрыва пласта.Investigation of the effect of biodegradable breakers on the rheological characteristics of fracturing fluids

Clinical effects of cannabis compared to synthetic cannabinoid receptor agonists (SCRAs): a retrospective cohort study of presentations with acute toxicity to European hospitals between 2013 and 2020.

INTRODUCTION Cannabis is the most common recreational drug worldwide and synthetic cannabinoid receptor agonists are currently the largest group of new psychoactive substances. The aim of this study was to compare the clinical features and outcomes of lone acute cannabis toxicity with lone acute synthetic cannabinoid receptor agonist toxicity in a large series of presentations to European emergency departments between 2013-2020. METHODS Self-reported drug exposure, clinical, and outcome data were extracted from the European Drug Emergencies Network Plus which is a surveillance network that records data on drug-related emergency department presentations to 36 centres in 24 European countries. Cannabis exposure was considered the control in all analyses. To compare the lone cannabis and lone synthetic cannabinoid receptor agonist groups, univariate analysis using chi squared testing was used for categorical variables and non-parametric Mann-Whitney U- testing for continuous variables. Statistical significance was defined as a P value of < 0.05. RESULTS Between 2013-2020 there were 54,314 drug related presentations of which 2,657 were lone cannabis exposures and 503 lone synthetic cannabinoid receptor agonist exposures. Synthetic cannabinoid receptor agonist presentations had statistically significantly higher rates of drowsiness, coma, agitation, seizures and bradycardia at the time of presentation. Cannabis presentations were significantly more likely to have palpitations, chest pain, hypertension, tachycardia, anxiety, vomiting and headache. DISCUSSION Emergency department presentations involving lone synthetic cannabinoid receptor agonist exposures were more likely to have neuropsychiatric features and be admitted to a psychiatric ward, and lone cannabis exposures were more likely to have cardiovascular features. Previous studies have shown variability in the acute toxicity of synthetic cannabinoid receptor agonists compared with cannabis but there is little comparative data available on lone exposures. There is limited direct comparison in the current literature between lone synthetic cannabinoid receptor agonist and lone cannabis exposure, with only two previous poison centre series and two clinical series. Whilst this study is limited by self-report being used to identify the drug(s) involved in the presentations, previous studies have demonstrated that self-report is reliable in emergency department presentations with acute drug toxicity. CONCLUSION This study directly compares presentations with acute drug toxicity related to the lone use of cannabis or synthetic cannabinoid receptor agonists. It supports previous findings of increased neuropsychiatric toxicity from synthetic cannabinoid receptor agonists compared to cannabis and provides further data on cardiovascular toxicity in lone cannabis use

Glial contribution to excitatory and inhibitory synapse loss in neurodegeneration

Synapse loss is an early feature shared by many neurodegenerative diseases, and it represents the major correlate of cognitive impairment. Recent studies reveal that microglia and astrocytes play a major role in synapse elimination, contributing to network dysfunction associated with neurodegeneration. Excitatory and inhibitory activity can be affected by glia-mediated synapse loss, resulting in imbalanced synaptic transmission and subsequent synaptic dysfunction. Here, we review the recent literature on the contribution of glia to excitatory/inhibitory imbalance, in the context of the most common neurodegenerative disorders. A better understanding of the mechanisms underlying pathological synapse loss will be instrumental to design targeted therapeutic interventions, taking in account the emerging roles of microglia and astrocytes in synapse remodeling

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Bildung im Sport? Entwicklung eines Fragebogens zur Erfassung von Bildungserwartungen von Schüler:innen an den Sportunterricht

Gröben B, Akbulut F, Braksiek M, Meier C, Heim C. Bildung im Sport? Entwicklung eines Fragebogens zur Erfassung von Bildungserwartungen von Schüler:innen an den Sportunterricht. In: Golenia M, Jürgens M, Kohake K, Neuber N, eds. Wissenstransfer – ein zentrales Thema für die Sportpädagogik? 35. Jahrestagung der dvs-Sektion Sportpädagogik vom 16.-18. Juni 2022. Münster: Westfälische Wilhelms-Universität; 2022: 88

The long shadow of our chemical past – High DDT concentrations in fish near a former agrochemicals factory in England

A total of 81 roach (Rutilus rutilus) collected from 13 southern English river sites between 2007 and 2012, were analysed for organochlorine pesticides, PCBs, PBDEs and some metals. Unexpectedly high concentrations of the banned insecticide DDT and its degradation products DDE and DDD (∑DDTs) were found in the 10 fish from the river Lee (or Lea) which averaged 88 ± 70 (standard deviation) μg/kg ww, almost 20 times higher than the average for the remaining sites (4.8 ± 3.1 μg/kg). All fish from that site exceeded the Canadian Tissue Residue Guideline (environmental quality standard) of 14 μg/kg ∑DDTs. Concentrations of the insecticides chlordane and lindane as well as copper, which is often used as a fungicide, were also elevated in fish from the Lee, though not as much as those of DDTs. A likely explanation for these observations was found in a nearby former pesticide factory, which had stopped production about three decades earlier. An extensive review of recent literature data on DDT in wild European fish found that, while levels are now generally low, there were several other hotspots with ∑DDTs levels that may still be of concern