Current Updates in Gene Therapy for Multiple Sclerosis

Background: Multiple sclerosis (MS) is the most common demyelinating disease affecting predominantly young adults. The underlying pathogenesis isn’t fully understood although autoimmune attacks against proteins in the CNS is the most accepted theory. Oligodendrocytes seem to be the most involved resulting in demyelinated axons. Currently, the management of MS focuses on relieving symptoms during acute attacks and preventing disease progression using disease-odifying agents such as interferon-beta, dimethyl fumarate, natalizumab, and fingolimod. Studies have proven long-term improvement on these drugs. However, possible side effects and curatively inducing or improving the repair process are major challenges.Al-Quds Universit

Association of serum leptin and ghrelin levels with smoking status on body weight: a systematic review and meta-analysis

Background and aimsSmoking cigarettes is a major global health problem that affects appetite and weight. The aim of this systematic review was to determine how smoking affected plasma leptin and ghrelin levels.MethodsA comprehensive search of PubMed, Scopus, Web of Science, and Ovid was conducted using a well-established methodology to gather all related publications.ResultsA total of 40 studies were included in the analysis of 11,336 patients. The overall effect showed a with a mean difference (MD) of −1.92[95%CI; −2.63: −1.20] and p = 0.00001. Subgroup analysis by study design revealed significant differences as well, but with high heterogeneity within the subgroups (I2 of 82.3%). Subgroup by sex showed that there was a significant difference in mean difference between the smoking and non-smoking groups for males (MD = −5.75[95% CI; −8.73: −2.77], p = 0.0002) but not for females (MD = −3.04[95% CI; −6.6:0.54], p = 0.10). Healthy, pregnant, diabetic and CVD subgroups found significant differences in the healthy (MD = −1.74[95% CI; −03.13: −0.35], p = 0.01) and diabetic (MD = −7.69[95% CI, −1.64: −0.73], p = 0.03). subgroups, but not in the pregnant or cardiovascular disease subgroups. On the other hand, the meta-analysis found no statistically significant difference in Ghrelin serum concentration between smokers and non-smokers (MD = 0.52[95% CI, −0.60:1.63], p = 0.36) and observed heterogeneity in the studies (I2 = 68%).ConclusionThis study demonstrates a correlation between smoking and serum leptin/ghrelin levels, which explains smoking’s effect on body weight.Systematic review registrationhttps://www.crd.york.ac.uk/ prospero/display_record.php, identifier (Record ID=326680)

Efficacy and safety of edaravone dexborneol in acute ischemic stroke: systematic review and meta-analysis

BackgroundEdaravone dexborneol represents a novel neuroprotective agent utilized in the treatment of acute ischemic stroke (AIS). Preliminary studies indicate that this combination exhibits enhanced therapeutic effects when compared to the use of edaravone alone. The objective of this study was to assess the efficacy and safety of edaravone dexborneol in the management of AIS.MethodThis systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. A comprehensive search of the PubMed, Cochrane Central, Scopus, and Web of Science databases was performed on December 30, 2024. Subsequently, we screened articles for eligibility, relevant data were extracted, and the risk of bias was assessed utilizing the Cochrane Collaboration Tool 2. The primary outcome evaluated was the efficacy of edaravone dexborneol in the management of AIS, as measured by the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). Secondary outcomes encompassed improvements in activities of daily living (ADL), reductions in post-stroke depression, inflammation, and hemorrhagic transformation, as well as enhancements in cognitive function, as indicated by Montreal Cognitive Assessment (MoCA) scores. Extracted data from pertinent Randomized Controlled Trials (RCTs) were analyzed using R programming for Windows. All procedures outlined in this study were pre-specified, and the protocol has been registered with PROSPERO under the unique identifier CRD42024626320.ResultsA total of six randomized controlled trials (RCTs) and one cohort study, all conducted in China and involving 2,942 patients with ischemic stroke (65.6% male), were included. Treatment regimens consisted of intravenous or sublingual edaravone dexborneol administered for 10–14 days. The pooled analysis of functional outcomes at 90 days, based on five studies, demonstrated a significant benefit, with a 39.5% higher likelihood of achieving favorable mRS scores (OR = 1.40, 95% CI: 1.18–1.65, p = 0.0001), without evidence of heterogeneity (I2 = 0%). In contrast, pooled analysis of NIHSS outcomes across seven studies using a random-effects model was not significant (SMD = −0.113, 95% CI: −0.333 to 0.107, p = 0.314), with substantial heterogeneity (I2 = 72.7%). However, under the common-effect model, a small but statistically significant benefit was observed (SMD = −0.083, 95% CI: −0.159 to −0.008, p = 0.030). Sensitivity analyses indicated that several studies (Fu 2024, Hu 2023, Xu 2019, Xu 2024) attenuated the pooled effect, while exclusion of Li 2024 and Hu 2023 reduced heterogeneity to 40.7% but resulted in only borderline significance. Secondary endpoints consistently demonstrated favorable effects, including improved activities of daily living, enhanced cognitive function (MoCA scores), and reduced rates of post-stroke depression, inflammation, and hemorrhagic transformation. Safety analyses revealed that adverse events were generally mild and comparable to controls, with some evidence suggesting a reduction in serious complications such as hemorrhagic transformation.ConclusionEdaravone dexborneol exhibits considerable potential as a neuroprotective agent in the context of AIS, providing both functional and cognitive advantages, alongside a favorable safety profile. The promising efficacy of this compound underscores the necessity for further comprehensive global studies aimed at optimizing its application and enhancing its relevance across diverse populations.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024626320

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of who surgical safety checklist use and mortality after emergency laparotomy

Background: The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods: In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results: Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89⋅6 per cent) compared with that in countries with a middle (753 of 1242, 60⋅6 per cent; odds ratio (OR) 0⋅17, 95 per cent c.i. 0⋅14 to 0⋅21, P &lt; 0⋅001) or low (363 of 860, 42⋅2 percent; OR 0⋅08, 0⋅07 to 0⋅10, P &lt; 0⋅001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference −9⋅4 (95 per cent c.i. −11⋅9 to −6⋅9) per cent; P &lt; 0⋅001), but the relationship was reversed in low-HDI countries (+12⋅1 (+7⋅0 to +17⋅3) per cent; P &lt; 0⋅001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0⋅60, 0⋅50 to 0⋅73; P &lt; 0⋅001). The greatest absolute benefit was seen for emergency surgery in low-and middle-HDI countries. Conclusion: Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone