Developmental abnormalities in cortical GABAergic system in mice lacking mGlu3 metabotropic glutamate receptors

Polymorphic variants of the gene encoding for metabotropic glutamate receptor 3 (mGlu3) are linked to schizophrenia. Because abnormalities of cortical GABAergic interneurons lie at the core of the pathophysiology of schizophrenia, we examined whether mGlu3 receptors influence the developmental trajectory of cortical GABAergic transmission in the postnatal life. mGlu3-/- mice showed robust changes in the expression of interneuron-related genes in the prefrontal cortex (PFC), including large reductions in the expression of parvalbumin (PV) and the GluN1 subunit of NMDA receptors. The number of cortical cells enwrapped by perineuronal nets was increased in mGlu3-/- mice, suggesting that mGlu3 receptors shape the temporal window of plasticity of PV+ interneurons. Electrophysiological measurements of GABAA receptor-mediated responses revealed a more depolarized reversal potential of GABA currents in the somata of PFC pyramidal neurons in mGlu3-/- mice at postnatal d 9 associated with a reduced expression of the K+/Cl- symporter. Finally, adult mGlu3-/- mice showed lower power in electroencephalographic rhythms at 1-45 Hz in quiet wakefulness as compared with their wild-type counterparts. These findings suggest that mGlu3 receptors have a strong impact on the development of cortical GABAergic transmission and cortical neural synchronization mechanisms corroborating the concept that genetic variants of mGlu3 receptors may predispose to psychiatric disorders.-Imbriglio, T., Verhaeghe, R., Martinello, K., Pascarelli, M. T., Chece, G., Bucci, D., Notartomaso, S., Quattromani, M., Mascio, G., Scalabrì, F., Simeone, A., Maccari, S., Del Percio, C., Wieloch, T., Fucile, S., Babiloni, C., Battaglia, G., Limatola, C., Nicoletti, F., Cannella, M. Developmental abnormalities in cortical GABAergic system in mice lacking mGlu3 metabotropic glutamate receptors

Prehospital intravenous fentanyl to patients with hip fracture: an observational cohort study of risk factors for analgesic non-treatment

BACKGROUND: Patients with proximal femoral neck fracture have a high short-term mortality, a high risk of postoperative complications, and impaired quality of life. One of the challenges related to the prehospital treatment of these patients is to administer systemic opioids fast and properly. Effective analgesic prehospital treatment ought be initiated rapidly in order to alleviate the stress that follows acute pain, to facilitate transportation, and to improve quality of care. The objectives of this study were to explore the prevalence of prehospital administration of intravenous fentanyl to patients with proximal femoral neck fracture in the ambulances and to assess risk factors for analgesic non-treatment.METHODS: This was a register-based observational cohort study of patients with proximal femoral neck fracture from the North Denmark Region transported by ambulance. The patients were identified via the Danish Interdisciplinary Hip Fracture Registry over a 3-year period from 1 July 2011 to 30 June 2014. This hospital registry contains data on several patient characteristics used for the risk factor analysis. Data on prehospital treatment (intravenous fentanyl) and patient monitoring were registered in an electronic prehospital patient record. A modified Poisson regression with robust standard errors was carried out with intravenous fentanyl as the primary binary outcome and the following explanatory variables: age, sex, Charlson Comorbidity Index score, housing, body mass index, type of fracture, fracture displacement, prior consultation with general practitioner, dispatch triage level, and time with ambulance personnel.RESULTS: In total, 2,140 patients with proximal femoral neck fracture were transported by ambulance, of which 584 (27.3%, 95% CI: 25.4-29.2) were treated with intravenous fentanyl. Risk factors for non-treatment were: older age, male sex (RR 0.77, 95% CI: 0.64-0.91), institutional housing (RR 0.72, 95% CI: 0.56-0.92), medial fracture (RR 0.74, 95% CI: 0.60-0.92), short time with ambulance personnel, Charlson Comorbidity Index score &gt; 1, year of fracture (2011), low levels of urgency at dispatch, and if seen by general practitioners prior to transport.DISCUSSION: Education of ambulance personnel in assessing and treating patients with hip fracture seems to be required. Also, future studies should consider alternative or supportive pain treatment options with suitable analgesic effects and side effects.CONCLUSIONS: Few patients with proximal femoral neck fracture were treated with intravenous fentanyl, and several risk factors were associated with prehospital analgesic non-treatment. Future prospective studies should explore covariates of socioeconomic, cultural, and psychological origin to provide further insight into the multifactorial causes of non-treatment of acute pain.</p

Preoperative Localization in Colonic Surgery (PLoCoS Study): a multicentric experience on behalf of the Italian Society of Colorectal Surgery (SICCR)

The aim of this prospective multicentric study was to compare the accurate colonic lesion localization ratio between CT and colonoscopy in comparison with surgery. All consecutive patients from 1st January to 31st December 2019 with a histologically confirmed diagnosis of dysplastic adenoma or adenocarcinoma with planned elective, curative colonic resection who underwent both colonoscopy and CT scans were included. Each patient underwent conventional colonoscopy and CT to stage the tumour, and the localization results of each procedure were registered. CT and colonoscopic localization were compared with surgical localization, adopted as the reference. Our analysis included 745 patients from 23 centres. After comparing the accuracy of colonoscopy and CT (for visible lesions) in localizing colonic lesions, no significant differences were found between the two preoperative tools (510/661 vs 499/661 correctly localized lesions, p = 0.518). Furthermore, after analysing only the patients who underwent complete colonoscopy and had a visible lesion on CT, no significant difference was observed between conventional colonoscopy and CT (331/427 vs 340/427, p = 0.505). Considering the intraoperative localization results as a reference, a comparison between colonoscopy and CT showed that colonoscopy significantly failed to correctly locate the lesions localized in the descending colon (17/32 vs 26/32, p = 0.031). We did not identify an advantage in using CT to localize colonic tumours. In this setting, colonoscopy should be considered the reference to properly localize lesions; however, to better identify lesions in the descending colon, CT could be considered a valuable tool to improve the accuracy of lesion localization

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien–Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4–7) and 7 (6–8) days respectively (P &lt; 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients