ABSTRACT
BACKGROUND: Donepezil, a cholinesterase inhibitor approved in Alzheimer's disease, has demonstrated analgesic and preventive effects in animal models of oxaliplatin-induced neuropathy. To improve the clinical interest of donepezil for the management and prevention of chemotherapy-induced peripheral neuropathy (CIPN), a broader validation is required in different animal models of CIPN. METHODS: using rat models of CIPN (bortezomib, paclitaxel, and vincristine), the analgesic and preventive efficacies of donepezil were evaluated on tactile, cold and heat hypersensitivities. The involvement of muscarinic M2 acetylcholine receptors (m2AChRs) in analgesic effects was investigated at the spinal level. The absence of interference of donepezil with the cytotoxic effect of chemotherapy has been controlled in cancer cell lines. RESULTS: the analgesic efficacy of donepezil was demonstrated for all CIPN models, mainly on tactile hypersensitivity (maximal efficacy at 60 min, p < 0.05 vs. vehicle group). This effect was suppressed by an intrathecal injection of methoctramine (m2AChR antagonist). Regarding preventive effects, donepezil limited tactile hypersensitivity induced by paclitaxel, but not for other CIPN models. Donepezil did not modify the viability of cancer cells or the efficacy of anticancer drugs. CONCLUSIONS: donepezil had a broad analgesic effect on animal models of CIPN and this effect involved spinal m2AChRs. This work validates the repositioning of donepezil in the management of CIPN.
Subject(s)
Antineoplastic Agents , Leukemia, Myeloid, Acute , Peripheral Nervous System Diseases , Acetylcholine , Analgesics/adverse effects , Animals , Antineoplastic Agents/toxicity , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/therapeutic use , Donepezil , Models, Animal , Paclitaxel/adverse effects , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/drug therapy , Peripheral Nervous System Diseases/prevention & control , Rats , Receptor, Muscarinic M2 , Receptors, MuscarinicABSTRACT
AIM OF THE STUDY: To review and to analyse the feasibility of using no urinary catheter or a catheter for less than 24 h compared with longer post-operative catheter after colorectal surgery with infraperitoneal dissection. METHODS: We performed a systematic review and meta-analysis of studies comparing no urinary catheter or a catheter for less than 24 h (early removal, ER) and urinary catheter drainage for 2 days or longer (late removal, LR) after colorectal surgery with infraperitoneal dissection. Primary endpoint was acute urinary retention (AUR) requiring a re-catheterization. Secondary endpoints were urinary tract infection (UTI), overall morbidity and hospital length of stay. Meta-analysis met the PRISMA criteria, with a random model. RESULTS: Out of 3659 articles found, 82 comparative studies on catheter duration were selected, of which five were in colorectal surgery: three randomized trials, one retrospective and one prospective series. There were 396 ER and 410 LR patients. All had undergone surgery with infraperitoneal dissection. There was no significant difference regarding AUR (OR = 2.09 [95%CI 0.97-4.52]) but significantly less UTI (OR = 0.39 [95%CI 0.22-0.67]) for early urinary catheter removal. The number needed to harm was much higher for AUR than for UTI (23.3 vs. 8). CONCLUSION: This meta-analysis suggests that, in terms of benefit/risk ratio, in colorectal surgery with infraperitoneal anastomosis, early removal (< 24 h) of the urinary catheter would be beneficial (because of a more frequent UTI after LR than AUR after ER) and would reduce the occurrence of UTI if no AUR risk factors are present. However, these findings should be interpreted with caution because of the low quality of evidence.
Subject(s)
Colorectal Surgery , Urinary Tract Infections , Anastomosis, Surgical/adverse effects , Catheters, Indwelling , Device Removal , Humans , Prospective Studies , Retrospective Studies , Time Factors , Urinary Catheterization , Urinary Catheters/adverse effects , Urinary Tract Infections/epidemiology , Urinary Tract Infections/etiology , Urinary Tract Infections/prevention & controlABSTRACT
INTRODUCTION: The COVID-19 pandemic is having a deep impact on our surgical practice and scientific publishing output. METHODS: The 100 best-ranked "surgery journals" were selected. The contents of the March, April, May, and June 2020 issues and ahead-of-print articles were screened. The retrieved articles on COVID-19 were separated into two categories: "opinion articles" and "scientific articles," i.e., randomized trials and original articles with structured methods and results. The number of COVID articles published in the TOP-10 journals was compared with that of COVID articles published elsewhere. RESULTS: There were 59 COVID original articles (8%). The great majority of articles were opinion articles (83.4%). Almost 40% of COVID articles were published in the TOP-10 journals. CONCLUSION: Original COVID articles (the core of our knowledge) are scant. Faced with a novel disease, neither the authors nor the editors should be criticized regarding this situation. The future step should be to publish high-quality papers in the setting of a major health crisis.