Moderate Intra-Abdominal Pressure Levels in Robot-Assisted Radical Prostatectomy Seem to Have No Negative Impact on Clinical Outcomes.

Introduction: Radical prostatectomy is increasingly performed laparoscopically with robot assistance (RALRP). RALRP, as with all laparoscopic procedures, requires a pneumoperitoneum, which might result in peritoneal inflammatory response reactions and postoperative pain. The aim of this retrospective single-centre study was to analyse the effects of a pneumoperitoneum during RARLP on clinical outcomes. Methods: All patients who underwent robot-guided prostatectomy in our clinic were included, with the exception of patients who were converted to open prostatectomy. C-reactive protein was used as a marker for the primary outcome, namely the postoperative inflammatory response. Intra-abdominal pressure (IAP) was evaluated as a potential factor influencing inflammation. In addition, the waist-hip ratio was used to estimate the amount of visceral adipose tissue, and the administration of dexamethasone was considered as a factor influencing inflammation. The Visual Analogue Scale (VAS) was used to determine postoperative pain. Patients were consecutively recruited between 1 September 2020 and 31 March 2022. Results: A total of 135 consecutive patients were included. The median waist-hip ratio was 0.55. The median duration of the pneumoperitoneum was 143 min. The median values of the average and maximum IAP values were 10 mmHg and 15 mmHg, respectively. The mean CRP of the first postoperative day was 6.2 mg/dL. The median VAS pain level decreased from 2 to 1 from the first to the third postoperative day. On the first postoperative day, 16 patients complained of shoulder pain. In addition, 134 patients were given some form of opioid pain treatment following surgery. Conclusion: We could not identify any relevant associations between the duration and IAP of the pneumoperitoneum and the indirect markers of inflammation or indicators of pain, or between the latter and the amount of visceral adipose tissue. In addition, we found no significant effect of the administration of dexamethasone on postoperative inflammation. The results point to a noninferior tolerability of moderate pressure during the procedure compared to the commonly utilised higher pressure, yet this must be confirmed in randomised controlled trials.

Therapy and Outcome of Prolonged Veno-Venous ECMO Therapy of Critically Ill ARDS Patients.

Veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) therapy has become increasingly used and established in many hospitals as a routine treatment. With ECMO-therapy being a resource-demanding procedure, it is of interest whether a more prolonged VV-ECMO treatment would hold sufficient therapeutic success. Our retrospective study included all VV-ECMO runs from 1 January 2020 to 31 June 2022. We divided all runs into four groups (<14 days, 14-27, 28-49, 50+) of different durations and looked for differences overall in hospital survival. Additionally, corresponding treatments and therapeutic modalities, as well as laboratory results, were analyzed. We included 117 patients. Of those, 97 (82.9%) received a VV-ECMO treatment longer than two weeks. We did not find a significant association between ECMO duration (p = 0.15) and increased mortality though a significant correlation between the patients' age and their probability of survival (p = 0.02). Notably, we found significantly lower interleukin-6 levels with an increase in therapy duration (p < 0.01). Our findings show no association between the duration of ECMO therapy and mortality. Thus, the treatment duration alone may not be used for making assumptions about the prospect of survival. However, attention is also increasingly focused on long-term outcomes, such as post-intensive care syndrome with severe impairments.

Prevalence of acute neurological complications and pathological neuroimaging findings in critically ill COVID-19 patients with and without VV-ECMO treatment.

Acute brain injuries such as intracerebral hemorrhage (ICH) and ischemic stroke have been reported in critically ill COVID-19 patients as well as in patients treated with veno-venous (VV)-ECMO independently of their COVID-19 status. The purpose of this study was to compare critically ill COVID-19 patients with and without VV-ECMO treatment with regard to acute neurological symptoms, pathological neuroimaging findings (PNIF) and long-term deficits. The single center study was conducted in critically ill COVID-19 patients between February 1, 2020 and June 30, 2021. Demographic, clinical and laboratory parameters were extracted from the hospital's databases. Retrospective imaging modalities included head computed tomography (CT) and magnetic resonance imaging (MRI). Follow-up MRI and neurological examinations were performed on survivors > 6 months after the primary occurrence. Of the 440 patients, 67 patients received VV-ECMO treatment (15%). Sixty-four patients (24 with VV-ECMO) developed acute neurological symptoms (pathological levels of arousal/brain stem function/motor responses) during their ICU stay and underwent neuroimaging with brain CT as the primary modality. Critically ill COVID-19 patients who received VV-ECMO treatment had a significantly lower survival during their hospital stay compared to those without (p < 0.001). Among patients treated with VV-ECMO, 10% showed acute PNIF in one of the imaging modalities during their ICU stay (vs. 4% of patients in the overall COVID-19 ICU cohort). Furthermore, 9% showed primary or secondary ICH of any severity (vs. 3% overall), 6% exhibited severe ICH (vs. 1% overall) and 1.5% were found to have non-hemorrhagic cerebral infarctions (vs. < 1% overall). There was a weak, positive correlation between patients treated with VV-ECMO and the development of acute neurological symptoms. However, the association between the VV-ECMO treatment and acute PNIF was negligible. Two survivors (one with VV-ECMO-treatment/one without) showed innumerable microhemorrhages, predominantly involving the juxtacortical white matter. None of the survivors exhibited diffuse leukoencephalopathy. Every seventh COVID-19 patient developed acute neurological symptoms during their ICU stay, but only every twenty-fifth patient had PNIF which were mostly ICH. VV-ECMO was found to be a weak risk factor for neurological complications (resulting in a higher imaging rate), but not for PNIF. Although logistically complex, repeated neuroimaging should, thus, be considered in all critically ill COVID-19 patients since ICH may have an impact on the treatment decisions and outcomes.

Neuroligin-3 Regulates Excitatory Synaptic Transmission and EPSP-Spike Coupling in the Dentate Gyrus In Vivo.

Neuroligin-3 (Nlgn3), a neuronal adhesion protein implicated in autism spectrum disorder (ASD), is expressed at excitatory and inhibitory postsynapses and hence may regulate neuronal excitation/inhibition balance. To test this hypothesis, we recorded field excitatory postsynaptic potentials (fEPSPs) in the dentate gyrus of Nlgn3 knockout (KO) and wild-type mice. Synaptic transmission evoked by perforant path stimulation was reduced in KO mice, but coupling of the fEPSP to the population spike was increased, suggesting a compensatory change in granule cell excitability. These findings closely resemble those in neuroligin-1 (Nlgn1) KO mice and could be partially explained by the reduction in Nlgn1 levels we observed in hippocampal synaptosomes from Nlgn3 KO mice. However, unlike Nlgn1, Nlgn3 is not necessary for long-term potentiation. We conclude that while Nlgn1 and Nlgn3 have distinct functions, both are required for intact synaptic transmission in the mouse dentate gyrus. Our results indicate that interactions between neuroligins may play an important role in regulating synaptic transmission and that ASD-related neuroligin mutations may also affect the synaptic availability of other neuroligins.

Institutional gender mainstreaming in health in UN Agencies: Promising strategies and ongoing challenges.

While the United Nations has long implemented strategies to tackle deep-rooted gender-based inequalities and discrimination in its programmes and policies, there is limited evidence on successful strategies to foster institutional structures and practices that promote gender equality or institutional gender mainstreaming. This paper explores and analyses the experience of institutional gender mainstreaming within UN Agencies working on global health, highlighting potential areas for learning. Overall, progress on institutional gender mainstreaming has been modest, with slow increases (if any) in investments in financial and human resources. The findings highlight the importance of well-established strategies, such as enforcing accountability, a robust gender architecture, and a cohesive capacity-building policy. Drawing on the experiences of gender experts, the paper shows that equally or more critical to the success of institutional gender mainstreaming were approaches such as leveraging strategic internal and external support and identifying strategic entry points for gender mainstreaming. There is considerable scope for strengthening gender mainstreaming within UN Agencies by reviewing and learning from UN system successes. In addition to learning from practice, the way forward lies in making visible and developing strategies to challenge embedded patriarchal organisational norms and systems.

[Management of Massive Intraoperative Blood Loss Using a Case Study]. / Management des massiven intraoperativen Blutverlusts anhand eines Fallbeispiels.

Massive intraoperative bleeding is a major and potentially life-threatening complication during surgical procedures. The lethal triade of hemorrhagic shock with metabolic acidosis, hypothermia and coagulopathy enhances bleeding tendency. Avoiding this vitious circle requires a well-structured and standardized procedure. Primary goals include the maintenance of adequate tissue oxygenation, restauration of proper coagulatory function, normothermia and homeostasis of acid-base and electrolyte balance. In the present article, these therapeutic goals and their pathophysiological background are illustrated with a clinical case example.

Forebrain-specific loss of synaptic GABAA receptors results in altered neuronal excitability and synaptic plasticity in mice.

Mutations that result in the defective trafficking of γ2 subunit containing GABAA receptors (γ2-GABAARs) are known to reduce synaptic inhibition. Whether perturbed clustering of non-mutated GABAARs similarly reduces synaptic inhibition in vivo is less clear. In this study we provide evidence that the loss of postsynaptic γ2-GABAARs upon postnatal ablation of gephyrin, the major scaffolding protein of inhibitory postsynapses, from mature principal neurons within the forebrain results in reduced induction of long-term potentiation (LTP) and impaired network excitability within the hippocampal dentate gyrus. The preferential reduction in not only synaptic γ2-GABAAR cluster number at dendritic sites but also the decrease in γ2-GABAAR density within individual clusters at dendritic inhibitory synapses suggests that distal synapses are more sensitive to the loss of gephyrin expression than proximal synapses. The fact that these mice display behavioural features of anxiety and epilepsy emphasises the importance of postsynaptic γ2-GABAAR clustering for synaptic inhibition.