The understanding of Parkinson's disease through genetics and new therapies

Introduction: Parkinson's disease is one of the progressive neurodegenerative diseases from which people suffer for years. The mechanism of this disease is associated with a decrease in the number of dopaminergic neurons in the substantia nigra (SN) while Lewy bodies are still present. As a result, both motor-ridity, tremor, and bradykinesia-and non-motor symptoms such as anxiety and depression. Nowadays, it is well known that the cause behind Parkinson's disease is mainly environmental changes, genetic susceptibility, and toxins. Unfortunately, there is no cure for the disease but treatments. The replacement of lost neurons, alpha-synuclein and apomorphine, is currently being studied for new therapies. This article focuses on history, mechanism, factors causing Parkinson's disease as well as future therapies for the cure of the diseases. Methodology: Data were collected from medical journals published on PubMed, The Lancet, Cells, and Nature Reviews Neurology databases with a predefined search strategy. All articles considering new therapies for Parkinson's disease were considered. Results: The pathophysiology of Parkinson's disease is currently reasonably understood. However, there is no definitive cure so all the treatments focus mainly on reducing or limiting the symptoms. Current treatment studies focus on genetics, replacing lost neurons, alpha-synuclein and apomorphine. Conclusion: Parkinson's disease is the most common movement disorder worldwide because of the loss of dopaminergic neurons in the substantia nigra. Its symptoms include motor dysfunctions such as rigidity, tremor, and bradykinesia and non-motor dysfunctions such as anxiety and depression. Through genetics, environmental changes and toxins analysis, it is now known that future new therapies are working on replacing lost neurons, alpha-synuclein and apomorphine

External validation and recalibration of an incidental meningioma prognostic model - IMPACT: protocol for an international multicentre retrospective cohort study

Introduction: Due to the increased use of CT and MRI, the prevalence of incidental findings on brain scans is increasing. Meningioma, the most common primary brain tumour, is a frequently encountered incidental finding, with an estimated prevalence of 3/1000. The management of incidental meningioma varies widely with active clinical-radiological monitoring being the most accepted method by clinicians. Duration of monitoring and time intervals for assessment, however, are not well defined. To this end, we have recently developed a statistical model of progression risk based on single-centre retrospective data. The model Incidental Meningioma: Prognostic Analysis Using Patient Comorbidity and MRI Tests (IMPACT) employs baseline clinical and imaging features to categorise the patient with an incidental meningioma into one of three risk groups: low, medium and high risk with a proposed active monitoring strategy based on the risk and temporal trajectory of progression, accounting for actuarial life expectancy. The primary aim of this study is to assess the external validity of this model. Methods and analysis: IMPACT is a retrospective multicentre study which will aim to include 1500 patients with an incidental intracranial meningioma, powered to detect a 10% progression risk. Adult patients ≥16 years diagnosed with an incidental meningioma between 1 January 2009 and 31 December 2010 will be included. Clinical and radiological data will be collected longitudinally until the patient reaches one of the study endpoints: intervention (surgery, stereotactic radiosurgery or fractionated radiotherapy), mortality or last date of follow-up. Data will be uploaded to an online Research Electronic Data Capture database with no unique identifiers. External validity of IMPACT will be tested using established statistical methods. Ethics and dissemination: Local institutional approval at each participating centre will be required. Results of the study will be reported through peer-reviewed articles and conferences and disseminated to participating centres, patients and the public using social media

Global Incidence and Risk Factors Associated With Postoperative Urinary Retention Following Elective Inguinal Hernia Repair

Importance Postoperative urinary retention (POUR) is a well-recognized complication of inguinal hernia repair (IHR). A variable incidence of POUR has previously been reported in this context, and contradictory evidence surrounds potential risk factors.Objective To ascertain the incidence of, explore risk factors for, and determine the health service outcomes of POUR following elective IHR.Design, Setting, and Participants The Retention of Urine After Inguinal Hernia Elective Repair (RETAINER I) study, an international, prospective cohort study, recruited participants between March 1 and October 31, 2021. This study was conducted across 209 centers in 32 countries in a consecutive sample of adult patients undergoing elective IHR.Exposure Open or minimally invasive IHR by any surgical technique, under local, neuraxial regional, or general anesthesia.Main Outcomes and Measures The primary outcome was the incidence of POUR following elective IHR. Secondary outcomes were perioperative risk factors, management, clinical consequences, and health service outcomes of POUR. A preoperative International Prostate Symptom Score was measured in male patients.Results In total, 4151 patients (3882 male and 269 female; median [IQR] age, 56 [43-68] years) were studied. Inguinal hernia repair was commenced via an open surgical approach in 82.2% of patients (n = 3414) and minimally invasive surgery in 17.8% (n = 737). The primary form of anesthesia was general in 40.9% of patients (n = 1696), neuraxial regional in 45.8% (n = 1902), and local in 10.7% (n = 446). Postoperative urinary retention occurred in 5.8% of male patients (n = 224), 2.97% of female patients (n = 8), and 9.5% (119 of 1252) of male patients aged 65 years or older. Risk factors for POUR after adjusted analyses included increasing age, anticholinergic medication, history of urinary retention, constipation, out-of-hours surgery, involvement of urinary bladder within the hernia, temporary intraoperative urethral catheterization, and increasing operative duration. Postoperative urinary retention was the primary reason for 27.8% of unplanned day-case surgery admissions (n = 74) and 51.8% of 30-day readmissions (n = 72).Conclusions The findings of this cohort study suggest that 1 in 17 male patients, 1 in 11 male patients aged 65 years or older, and 1 in 34 female patients may develop POUR following IHR. These findings could inform preoperative patient counseling. In addition, awareness of modifiable risk factors may help to identify patients at increased risk of POUR who may benefit from perioperative risk mitigation strategies

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care