Transvaginal hybrid NOTES cholecystectomy—results of a randomized clinical trial after 6 months

Introduction

For cholecystectomy (CHE), both the needlescopic three-trocar technique with 2–3-mm instruments (needlescopic cholecystectomy (NC)) and the umbilically assisted transvaginal technique with rigid instruments (transvaginal cholecystectomy (TVC)) have been established for further reduction of the trauma remaining from laparoscopy.

Methods

To compare the further outcome of both techniques for elective CHE in female patients, we analyzed the secondary end points of a prospective randomized single-center trial (needlescopic versus transvaginal cholecystectomy (NATCH) trial; ClinicalTrials.gov Identifier: NCT0168577), in particular, satisfaction with aesthetics, overall satisfaction, abdominal pain, and incidence of trocar hernias postoperatively at both 3 and 6 months. After 3 months, the domains “satisfaction” and “pain” of the German version of the Female Sexual Function Index (FSFI-d) were additionally evaluated to detect respective complications. A gynecological control examination was conducted in all TVC patients after 6 months.

Results

Forty patients were equally randomized into the therapy and the control groups between February 2010 and June 2012. No significant differences were found for overall satisfaction with the surgical result, abdominal pain, sexual function, and the rate of trocar hernias. However, aesthetics were rated significantly better by TVC patients both after 3 and after 6 months (P?=?0.004 and P?<?0.001). There were no postoperative pathological gynecological findings.

Conclusions

Following TVC, there is a significantly better aesthetic result as compared to NC, even at 3 and 6 months after the procedure. No difference was found for sexual function.     

Cell and chloroplast division requires ARTEMIS

Chloroplasts are endosymbiotic organelles of cyanobacterial origin. It seems reasonable to assume that cell division and organelle division still share general principles, as shown for the FtsZ proteins. However, further components involved in this process are largely unknown. Here we describe ARTEMIS, a nuclear-encoded protein of chloroplast inner envelope membranes that is required for organelle division. ARTEMIS consists of three distinct modules: an N-terminal receptor-like region, a centrally positioned glycine-rich stretch containing a nucleoside triphosphate-binding site, and a C-terminal YidC/Oxa1p/Alb3 protein translocase-like domain. Analysis of Arabidopsis En-1 transposon mutants as well as ARTEMIS antisense plants revealed chloroplasts arrested in the late stages of division. Chloroplasts showed clearly separated and distinct multiple thylakoid systems, whereas the final organelle fission remained unaccomplished. Inactivation of a cyanobacterial gene with sequence similarity to the YidC/Oxa1p/Alb3-like domain of ARTEMIS resulted in aberrant cell division, which could be rescued by the Arabidopsis protein. ARTEMIS represents a so-far-unrecognized link between prokaryotic cell fission and chloroplast division.     

Follow-up imaging after cryoablation of clear cell renal cell carcinoma is feasible using single photon emission computed tomography with 111In-girentuximab

European Journal of Nuclear Medicine and Molecular Imaging - Detection of residual or recurrent vital renal tumor on follow-up (FU) cross-sectional imaging after ablative therapy is challenging....     

Efficacy and safety of treatment with biologicals (benralizumab,dupilumab, mepolizumab,omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma

Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV₁, without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV₁. More data on long-term safety are needed together with more efficacy data in the paediatric population.     

Pathological responses to single‐pulse electrical stimuli in epilepsy: The role of feedforward inhibition

Delineation of epileptogenic cortex in focal epilepsy patients may profit from single‐pulse electrical stimulation during intracranial EEG recordings. Single‐pulse electrical stimulation evokes early and delayed responses. Early responses represent connectivity. Delayed responses are a biomarker for epileptogenic cortex, but up till now, the precise mechanism generating delayed responses remains elusive. We used a data‐driven modelling approach to study early and delayed responses. We hypothesized that delayed responses represent indirect responses triggered by early response activity and investigated this for 11 patients. Using two coupled neural masses, we modelled early and delayed responses by combining simulations and bifurcation analysis. An important feature of the model is the inclusion of feedforward inhibitory connections. The waveform of early responses can be explained by feedforward inhibition. Delayed responses can be viewed as second‐order responses in the early response network which appear when input to a neural mass falls below a threshold forcing it temporarily to a spiking state. The combination of the threshold with noisy background input explains the typical stochastic appearance of delayed responses. The intrinsic excitability of a neural mass and the strength of its input influence the probability at which delayed responses to occur. Our work gives a theoretical basis for the use of delayed responses as a biomarker for the epileptogenic zone, confirming earlier clinical observations. The combination of early responses revealing effective connectivity, and delayed responses showing intrinsic excitability, makes single‐pulse electrical stimulation an interesting tool to obtain data for computational models of epilepsy surgery.