Does surgeon or hospital volume influence outcome in dedicated colorectal units?-A Viennese perspective.

OBJECTIVE: A clear relationship between higher surgeon volume and improved outcomes has not been convincingly established in rectal cancer surgery. The aim of this study was to evaluate the impact of individual surgeon's caseload and hospital volume on perioperative outcome. METHODS: We retrospectively analyzed 336 consecutive patients undergoing oncological resection for rectal cancer at two Viennese hospitals between 1 January 2015 and 31 December 2020. The effect of baseline characteristics as well as surgeons' caseloads (low volume: 0-5 cases per year, high volume > 5 cases per year) on postoperative complication rates (Clavien-Dindo Classification groups of < 3 and ≥ 3) were evaluated. RESULTS: No differences in baseline characteristics were found between centers in terms of sex, smoking status, or comorbidities of patients. Interestingly, only 14.7% of surgeons met the criteria to be classified as high-volume surgeons, while accounting for 66.3% of all operations. There was a significant difference in outcomes depending on the treating center in univariate and multivariate binary logistic regression analysis (odds ratio (OR) = 2.403, p = 0.008). Open surgery was associated with lower complication rates than minimally invasive approaches in univariate analysis (OR = 0.417, p = 0.003, 95%CI = 0.232-0.739) but not multivariate analysis. This indicated that the center's policy rather than surgeon volume or mode of surgery impact on postoperative outcomes. CONCLUSION: Treating center standards impacted on outcome, while individual caseload of surgeons or mode of surgery did not independently affect complication rates in this analysis. The majority of rectal cancer resections are performed by a small number of surgeons in Viennese hospitals.

Age-Dependent and Pathway-Specific Bimodal Action of Nicotine on Synaptic Plasticity in the Hippocampus of Mice Lacking the miR-132/212 Genes.

Nicotine addiction develops predominantly during human adolescence through smoking. Self-administration experiments in rodents verify this biological preponderance to adolescence, suggesting evolutionary-conserved and age-defined mechanisms which influence the susceptibility to nicotine addiction. The hippocampus, a brain region linked to drug-related memory storage, undergoes major morpho-functional restructuring during adolescence and is strongly affected by nicotine stimulation. However, the signaling mechanisms shaping the effects of nicotine in young vs. adult brains remain unclear. MicroRNAs (miRNAs) emerged recently as modulators of brain neuroplasticity, learning and memory, and addiction. Nevertheless, the age-dependent interplay between miRNAs regulation and hippocampal nicotinergic signaling remains poorly explored. We here combined biophysical and pharmacological methods to examine the impact of miRNA-132/212 gene-deletion (miRNA-132/212-/-) and nicotine stimulation on synaptic functions in adolescent and mature adult mice at two hippocampal synaptic circuits: the medial perforant pathway (MPP) to dentate yrus (DG) synapses (MPP-DG) and CA3 Schaffer collaterals to CA1 synapses (CA3-CA1). Basal synaptic transmission and short-term (paired-pulse-induced) synaptic plasticity was unaltered in adolescent and adult miRNA-132/212-/- mice hippocampi, compared with wild-type controls. However, nicotine stimulation promoted CA3-CA1 synaptic potentiation in mature adult (not adolescent) wild-type and suppressed MPP-DG synaptic potentiation in miRNA-132/212-/- mice. Altered levels of CREB, Phospho-CREB, and acetylcholinesterase (AChE) expression were further detected in adult miRNA-132/212-/- mice hippocampi. These observations propose miRNAs as age-sensitive bimodal regulators of hippocampal nicotinergic signaling and, given the relevance of the hippocampus for drug-related memory storage, encourage further research on the influence of miRNAs 132 and 212 in nicotine addiction in the young and the adult brain.

miRNA-132/212 Gene-Deletion Aggravates the Effect of Oxygen-Glucose Deprivation on Synaptic Functions in the Female Mouse Hippocampus.

Cerebral ischemia and its sequelae, which include memory impairment, constitute a leading cause of disability worldwide. Micro-RNAs (miRNA) are evolutionarily conserved short-length/noncoding RNA molecules recently implicated in adaptive/maladaptive neuronal responses to ischemia. Previous research independently implicated the miRNA-132/212 cluster in cholinergic signaling and synaptic transmission, and in adaptive/protective mechanisms of neuronal responses to hypoxia. However, the putative role of miRNA-132/212 in the response of synaptic transmission to ischemia remained unexplored. Using hippocampal slices from female miRNA-132/212 double-knockout mice in an established electrophysiological model of ischemia, we here describe that miRNA-132/212 gene-deletion aggravated the deleterious effect of repeated oxygen-glucose deprivation insults on synaptic transmission in the dentate gyrus, a brain region crucial for learning and memory functions. We also examined the effect of miRNA-132/212 gene-deletion on the expression of key mediators in cholinergic signaling that are implicated in both adaptive responses to ischemia and hippocampal neural signaling. miRNA-132/212 gene-deletion significantly altered hippocampal AChE and mAChR-M1, but not α7-nAChR or MeCP2 expression. The effects of miRNA-132/212 gene-deletion on hippocampal synaptic transmission and levels of cholinergic-signaling elements suggest the existence of a miRNA-132/212-dependent adaptive mechanism safeguarding the functional integrity of synaptic functions in the acute phase of cerebral ischemia.