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Background: Prostatectomy is associated with relevant acute postoperative pain. Optimal analgesic techniques to minimize pain and enhance recovery are still under investigation. We aimed to compare the effect of three different analgesic techniques on quality of recovery.Methods: This investigator-initiated, prospective, randomized, three-arm, parallel-group, active-controlled, interventional superiority trial was performed in a Swiss teaching hospital from 2018 to 2021. Consecutive patients undergoing open or robotic-assisted radical prostatectomy were randomized to spinal anaesthesia (SSS, bupivacaine 0.5% + fentanyl), bilateral transversus abdominis plane block (TAP, ropivacaine 0.375% + clonidine) or systemic administration of lidocaine (SA, lidocaine 1%) in addition to general anaesthesia. Primary outcome was quality of recovery 15 (QoR-15) score on postoperative day one compared to baseline. Secondary outcomes were QoR-15 at discharge, postoperative nausea and vomiting, pain scores, return of gastrointestinal function and use of rescue analgesia.Results: From 133 patients, 40 received spinal anaesthesia, 45 TAP block and 48 systemic analgesia. QoR-15 scores did not differ on day 1 (p = 0.301) or at discharge (p = 0.309) when compared to baseline. QoR-15 changes were similar in all groups. At discharge, median QoR-15 scores were considered as good (>122) in all groups: SSS 134 [IQR 128-138]; TAP 129 [IQR 122-136] and SA 128 [IQR 123-136]. There were no significant differences in the other secondary outcomes.Conclusions: Quality of recovery on postoperative day one compared to baseline did not differ if spinal anaesthesia, TAP block or systemic administration of lidocaine was added to general anaesthesia.Significance: Optimal analgesic techniques to enhance recovery after prostatectomy are still under investigation. In this 3-arm randomized controlled trial, addition of spinal anaesthesia or transversus abdominis plane block to general anaesthesia did not improve quality of recovery after radical prostatectomy compared to less invasive intravenous lidocaine infusion (standard of care/control group). Quality of recovery at the time of discharge was considered as good in all three groups. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether early acute kidney injury affects mid‐term renal function, to identify risk factors for impaired mid‐term renal function, and to highlight the evolution of plasma creatinine and estimated glomerular filtration rate in the first 12 months after cystectomy and urinary diversion. Methods: We conducted a single‐center retrospective observational cohort study from 2000 to 2019. We included 900 consecutive patients undergoing cystectomy and urinary diversion. Patients with incomplete data and preoperative hemodialysis were excluded. Early acute kidney injury was defined as an increase in plasma creatinine of >50% or >26.5 μmol/L within 24 h after surgery. Multiple linear regression analysis was performed to model the association between risk factors and change in plasma creatinine and estimated glomerular filtration rate at 12 months. Results: Early acute kidney injury was diagnosed in 183/900 patients (20.3%) and was associated with significant mid‐term plasma creatinine increase compared to preoperative value (+10.0 μmol/L [95% confidence interval −1.5, 25.0] vs +4.0 μmol/L [−7.0, 13.0]; P < 0.001). Similarly, a significant estimated glomerular filtration rate change was found (−11.2 mL/min [95% confidence interval −19.8, 0.6] vs −4.9 mL/min [−15.6, 5.3]; P < 0.001). In the linear regression model, early acute kidney injury increased creatinine at 12 months by 9.8% (estimated glomerular filtration rate: decrease by 6.2 mL/min), male sex by 12.0%. Limitations include retrospective analysis from prospectively assessed data. Conclusions: Early acute kidney injury resulted in elevated plasma creatinine and decreased estimated glomerular filtration rate values 12 months postoperatively, albeit the clinical relevance remains questionable. [ABSTRACT FROM AUTHOR]

Objective: To assess if uninterrupted anticoagulant agents' administration affects blood loss and blood transfusion during open radical cystectomy (RC) and urinary diversion. Patients and Methods: We conducted an observational single‐centre cohort study of a consecutive series of 1430 RC patients, between 2000 and 2020. Blood loss was depicted according to body weight and duration of surgery (mL/kg/h), and blood transfusion. The group 'with anticoagulant agents' was considered if surgery was performed with uninterrupted low‐dose aspirin (ASS), oral anticoagulants (OAC) with an international normalised ratio (INR) goal of 2–2.5 or bridging with therapeutic low‐molecular‐weight heparin (LMWH). Outcomes were intraoperative blood loss, blood transfusion rate (separately analysed if administered within 24 h perioperatively or >24 h after surgery) and the 90‐day major adverse cardiac events (MACE) rate. We used propensity score (PS)‐matching analysis to adjust for imbalances between groups with or without anticoagulant agents. Results: The PS‐matched median (interquartile range [IQR]) blood loss was 2.10 (1.50–2.94) mL/kg/h in patients with anticoagulant agents vs 2.11 (1.47–2.94) mL/kg/h without anticoagulant agents (Padj > 0.99). The PS‐matched blood transfusion rates were 26.2% vs 35.1% (Padj = 0.875) within 24 h perioperatively and 57.0% vs 55.0% (Padj = 0.680) if administered >24 h postoperatively. A sub‐analysis of the three different anticoagulant agents could not detect any significance between ASS, OAC, or LMWH. The PS‐matched incidence of MACE was 9.1% in the group with anticoagulant agents and 8.1% in those without anticoagulant agents (Padj > 0.99). Limitations include selection bias and retrospective analysis from prospectively assessed data. Conclusions: Perioperative continuation of ASS, uninterrupted OAC with low INR goal or bridging with LMWH had no impact on blood loss and transfusion rate in RC patients. Therefore, there might be no compulsory need for discontinuation of anticoagulant agents. [ABSTRACT FROM AUTHOR]

The activation of N‐methyl‐D‐aspartate receptors (NMDARs) in substantia nigra pars compacta (SNc) dopamine (DA) cells is central to generate the bursting activity, a phasic signal linked to DA‐related behaviours via the change in postsynaptic DA release. NMDARs are recruited during excitatory synaptic transmission by glutamate release, but the glycine site level of occupancy of these receptors during basal action potential‐dependent activity is not known for SNc DA neurons. We explored NMDAR‐dependent signals during exogenous applications of co‐agonists in midbrain slices from juvenile rats. We found that both glycine and D‐serine strengthened the NMDAR‐dependent component of excitatory postsynaptic currents (EPSCs) in a concentration‐dependent manner. EPSCs were also increased by endogenous glycine via the blockade of the glycine transport. The glycine site of NMDARs contributing to synaptic transmission is therefore subsaturated. The behaviourally relevant burst firing was more sensitive to exogenous D‐serine and endogenous glycine than to exogenous glycine. The mechanisms regulating the availability of the co‐agonists exert consequently a critical influence on the excitability of DA neurons via NMDARs. The modulation of the phasic firing in DA neurons by ambient NMDAR co‐agonists may be important for nigral information processing and downstream motor‐related behaviour. [ABSTRACT FROM AUTHOR]

Key points The hyperpolarization-activated cation current Ih is expressed in dopamine neurons of the substantia nigra, but the subcellular distribution of the current and its role in synaptic integration remain unknown., We used cell-attached patch recordings to determine the localization profile of Ih along the somatodendritic axis of nigral dopamine neurons in slices from young rats., Ih density is higher in axon-bearing dendrites, in a membrane area close to the axon origin, than in the soma and axon-lacking dendrites., Dual current-clamp recordings revealed a similar contribution of Ih to the waveform of single excitatory postsynaptic potentials throughout the somatodendritic domain., The Ih blocker ZD 7288 increased the temporal summation in all dendrites with a comparable effect in axon- and non-axon dendrites., The strategic position of Ih in the proximity of the axon may influence importantly transitions between pacemaker and bursting activities and consequently the downstream release of dopamine., Abstract Dendrites of most neurons express voltage-gated ion channels in their membrane. In combination with passive properties, active currents confer to dendrites a high computational potential. The hyperpolarization-activated cation current Ih present in the dendrites of some pyramidal neurons affects their membrane and integration properties, synaptic plasticity and higher functions such as memory. A gradient of increasing h-channel density towards distal dendrites has been found to be responsible for the location independence of excitatory postsynaptic potential (EPSP) waveform and temporal summation in cortical and hippocampal pyramidal cells. However, reports on other cell types revealed that smoother gradients or even linear distributions of Ih can achieve homogeneous temporal summation. Although the existence of a robust, slowly activating Ih current has been repeatedly demonstrated in nigral dopamine neurons, its subcellular distribution and precise role in synaptic integration are unknown. Using cell-attached patch-clamp recordings, we find a higher Ih current density in the axon-bearing dendrite than in the soma or in dendrites without axon in nigral dopamine neurons. Ih is mainly concentrated in the dendritic membrane area surrounding the axon origin and decreases with increasing distances from this site. Single EPSPs and temporal summation are similarly affected by blockade of Ih in axon- and non-axon-bearing dendrites. The presence of Ih close to the axon is pivotal to control the integrative functions and the output signal of dopamine neurons and may consequently influence the downstream coding of movement. [ABSTRACT FROM AUTHOR]

Key points Zinc inhibits ionotropic receptors commonly found at central synapses, as well as a wide variety of voltage-activated ion channels that modulate neuronal excitability and neurotransmitter release., We found that zinc chelation facilitated GABAergic signalling in dentate granule cells and that blocking T-type Ca2+ channel activity abolished this effect. Zinc chelation reduced spike threshold, increased spike width and shifted the input-output relationship in dentate interneurones, which is consistent with increased excitability., In granule cells, zinc chelation narrowed the window for the integration of glutamatergic inputs originating from perforant path synapses., These results demonstrate that zinc modulates dentate interneurone function and regulates spike routing to local and hippocampal targets., Abstract Zinc actions on synaptic transmission span the modulation of neurotransmitter receptors, transporters, activation of intracellular cascades and alterations in gene expression. Whether and how zinc affects inhibitory synaptic signalling in the dentate gyrus remains largely unexplored. We found that mono- and di-synaptic GABAergic inputs onto dentate granule cells were reversibly depressed by exogenous zinc application and enhanced by zinc chelation. Blocking T-type Ca2+ channels prevented the effect of zinc chelation. When recording from dentate fast-spiking interneurones, zinc chelation facilitated T-type Ca2+ currents, increased action potential half-width and decreased spike threshold. It also increased the offset of the input-output relation in a manner consistent with enhanced excitability. In granule cells, chelation of zinc reduced the time window for the integration of glutamatergic inputs originating from perforant path synapses, resulting in reduced spike transfer. Thus, zinc-mediated modulation of dentate interneurone excitability and GABA release regulates information flow to local targets and hippocampal networks. [ABSTRACT FROM AUTHOR]