Predicting liver function after hemihepatectomy in patients with hepatocellular carcinoma using different modalities.

In response to Dr. Yue et al's study on prognostic factors for post-hemihepatectomy outcomes in hepatocellular carcinoma (HCC) patients, this critical review identifies methodological limitations and proposes enhancements for future research. While the study identifies liver stiffness measure and standard residual liver volume as potential predictors, concerns regarding small sample size, reliance on biochemical markers for safety assessment, and inadequate adjustment for confounding variables are raised. Recommendations for rigorous methodology, including robust statistical analysis, consideration of confounding factors, and selection of outcome measures with clinical components, are proposed to strengthen prognostic assessments. Furthermore, validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hemihepatectomy.

Opium use and gastrointestinal cancers: a systematic review and meta-analysis study.

Aim: The current systematic review and meta-analysis aimed to assess the association between Gastrointestinal (GI) cancers and opium use. Background: GI malignancies are a global public health issue and are associated with many risk factors including genetic and lifestyle factors. Methods: PubMed, Web of Science, Embase and Scopus and the Google Scholar search engine in addition to Persian databases including Magiran and SID were searched using relevant keywords. The associations of opium use, long duration of opium use, high daily amount opium use and high cumulative opium use and GI cancer and various subtypes of GI cancers were estimated and pooled in format of odds ratios (OR) and their corresponding 95% confidence intervals (CI) with a random effects model. Results: 22 articles that were published between 1983 and 2022 entered the analyses. There were significant relationships between opium use based on crude effect sizes (OR: 2.53, 1.95-3.29) and adjusted effect sizes (OR: 2.64, 1.99-3.51), high daily opium use (or: 3.41, 1.92-6.06), long duration of opium use (OR: 3.03, 1.90-4.84) and high cumulative opium use (OR: 3.88, 2.35-6.41), all compared to never opium use, and GI cancer. The results were not sensitive to sensitivity analyses and no influential publication biases were found in these analyses. Conclusion: Our meta-analysis showed that opium use could be associated with increased risk of overall and some particular GI cancers including oropharyngeal, gastric, pancreatic and colorectal cancers. Opium use as a potentially modifiable factor, therefore, should be more emphasized.

Electrocardiographic findings in patients with sickle cell disease: A protocol for systematic review and meta-analysis.

Background: Despite advancements in the management of patients with sickle cell disease (SCD), the involvement of the cardiovascular system in these patients remains a significant concern. Cardiovascular manifestations of SCD are well-documented, with electrocardiography (ECG) serving as a valuable diagnostic tool. Studies have reported a high rate of critical ECG findings in patients with SCD that warrants consideration when managing these patients, indicating the need for proactive cardiac screening and management strategies in this patient population. This study aims to systematically review the literature to identify sociodemographic, clinical, and paraclinical factors associated with ECG abnormalities in patients with SCD. Methods: A comprehensive search strategy will be employed across multiple online databases, including PubMed, Embase, Scopus, Web of Science, and Google Scholar, for published and gray literature. Eligible studies will include original articles reporting associations between sociodemographic, clinical, and paraclinical variables and a spectrum of ECG findings in patients with SCD. Independent reviewers will conduct the screening, quality assessment, and data extraction. Quantitative analyses will be performed under a random-effect model using Comprehensive Meta-Analysis software, with subgroup analyses based on SCD status, sickle hemoglobinopathy form, and age group.

MASLD-Related HCC: A Comprehensive Review of the Trends, Pathophysiology, Tumor Microenvironment, Surveillance, and Treatment Options.

Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and a shift in the etiology of HCC, with MASLD replacing the hepatitis B virus as the primary contributor to new cases of HCC. MASLD-related HCC exhibits distinct characteristics compared to viral HCC, including unique immune cell profiles resulting in an overall more immunosuppressive or exhausted tumor microenvironment. Furthermore, MASLD-related HCC is frequently identified in older age groups and among individuals with cardiometabolic comorbidities. Additionally, a greater percentage of MASLD-related HCC cases occur in noncirrhotic patients compared to those with viral etiologies, hindering early detection. However, the current clinical practice guidelines lack specific recommendations for the screening of HCC in MASLD patients. The evolving landscape of HCC management offers a spectrum of therapeutic options, ranging from surgical interventions and locoregional therapies to systemic treatments, for patients across various stages of the disease. Despite ongoing debates, the current evidence does not support differences in optimal treatment modalities based on etiology. In this study, we aimed to provide a comprehensive overview of the current literature on the trends, characteristics, clinical implications, and treatment modalities for MASLD-related HCC.

The effect of the four pharmacological pillars of heart failure on haemoglobin level.

Anaemia, a condition characterized by low levels of haemoglobin, is frequently observed in patients with heart failure (HF). Guideline-directed medical therapy improves HF outcomes by using medications like beta blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, along with mineralocorticoid receptor antagonists and sodium-glucose cotransporter 2 inhibitors. In this study, we aimed to review the pathophysiology of anaemia in patients with HF and present the current evidence regarding the relationship between the main recommended medications for these patients and haemoglobin levels. The authors conducted a comprehensive search in the medical literature for relevant original clinical articles in which the four pharmacological pillars of HF were given to the patients; we, then, assessed whether the association of use of these medications and haemoglobin level or development of anaemia was provided. These common medications have been shown in the literature that may exacerbate or ameliorate anaemia. Besides, it has been shown that even in the case that they result in the development of anaemia, their use is associated with positive effects that outweigh this potential harm. The literature also suggests that among patients receiving medications with negative effects on the level of haemoglobin, there was no difference in the rate of mortality between anaemic and non-anaemic patients when both were on treatment for anaemia; this point highlights the importance of the detection and treatment of anaemia in these patients. Further research is needed to explore these relationships and identify additional strategies to mitigate the risk of anaemia in this population.

Electrocardiographic abnormalities in patients with sickle cell disease: A systematic review and meta-analysis.

BACKGROUND: Previous studies have documented that electrocardiography (ECG) can reveal a range of abnormalities, offering valuable insights into the cardiac evaluation of patients with sickle cell disease (SCD). The objective of this study is to assess the patterns of ECG abnormalities observed in these patients with SCD, and to determine their prevalence. METHOD: We systematically reviewed the literature using online databases of PubMed, Scopus, Web of Science, Embase, and Google Scholar to identify original studies that reported findings of standard ECG assessments in patients with SCD. Statistical analyses were performed using the random effects model. Additional analyses including sensitivity analysis and subgroup analysis were also conducted. RESULTS: Analysis of data from 59 studies involving 897,920 individuals with SCD revealed that 75% of these patients had abnormal ECG findings (67%-81%), which were predominantly nonspecific ST-T changes, left ventricular hypertrophy, T-wave changes, prolonged corrected QT (QTc) interval, and ischemic changes. Besides, it was shown that these patients had significantly higher odds of having any ECG abnormalities (OR of 17.50, 4.68-65.49), right atrial enlargement (6.09, 1.48-25.09), left ventricular hypertrophy (3.45, 1.73-6.89), right ventricular hypertrophy (7.18, 2.28-22.57), biventricular hypertrophy (10.11, 1.99-51.38), prolonged QTc interval (5.54, 2.44-12.59), ST depression (3.34, 1.87-5.97), and T-wave changes (5.41, 1.43-20.56). Moreover, the mean of QTc interval was significantly higher among those with SCD (23.51 milliseconds, 16.08-30.94). CONCLUSION: Our meta-analysis showed a higher prevalence of abnormal ECG findings among individuals with SCD. A significant proportion of these patients had various ECG abnormalities, suggesting a potential need for regular ECG assessments for patients with SCD.

Prevalence of metabolically healthy obesity and healthy overweight and the associated factors in southern Iran: A population-based cross-sectional study.

Background and Aims: Obesity is considered a major growing threat to public health which could negatively affect the quality of life. The current cross-sectional study was conducted to investigate the population-based prevalence of metabolically healthy obesity (MHO) and healthy overweight (MHOW) and associated factors in southern Iran. Methods: Baseline data from the Pars Cohort Study was analyzed. Metabolically healthy participants were identified based on the definition of the American Heart Association for the metabolic syndrome. The prevalence of MHOW and MHO and their 95% confidence intervals were estimated. Poisson regression was applied for the calculation of prevalence ratios (PRs). Results: Gender- and age-standardized prevalences of MHOW and MHO were 6.3% (6.0%-6.6%) and 2.3% (2.1%-2.5%), respectively. The following factors were associated with being MHOW compared with those with normal weight: Being younger, female gender (1.31, 1.20-1.43), higher socioeconomic status, being noncurrent cigarette smoker (1.27, 1.11-1.45), low level of physical activity (1.14, 1.03-1.25), having normal overweight during adolescence, and overweight (1.35, 1.24-1.48) or obesity (1.68, 1.53-1.86) during young adulthood. We also found strong associations between MHO and younger age groups, female gender (2.87, 2.40-3.42), being married (1.57, 1.08-2.27), Fars ethnicity (1.25, 1.10-1.43), higher socioeconomic status, ever use of tobacco (1.14, 1.00-1.30), never use of opium (1.85, 1.19-2.86), lower physical activity (1.45, 1.20-1.72), being normal weight in 15-year body pictogram and being overweight (1.87, 1.59-2.20) or obese (3.20, 2.74-3.72) in 30-year body pictogram when considering those with normal weight or MHO. Conclusion: Potentially modifiable factors including physical activity should be more emphasized. Furthermore, our study issued that it would be more reasonable that the prevention of unhealthy obesity be initiated before the development of MHO, where there are more protective factors and they could be more effective.

Machine-learning algorithms in screening for type 2 diabetes mellitus: Data from Fasa Adults Cohort Study.

INTRODUCTION: The application of machine learning (ML) is increasingly growing in biomedical sciences. This study aimed to evaluate factors associated with type 2 diabetes mellitus (T2DM) and compare the performance of ML methods in identifying individuals with the disease in an Iranian setting. METHODS: Using the baseline data from Fasa Adult Cohort Study (FACS) and in a sex-stratified manner, we studied factors associated with T2DM by applying seven different ML methods including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), K-Nearest Neighbours (KNN), Gradient Boosting Machine (GBM), Extreme Gradient Boosting (XGB) and Bagging classifier (BAG). We further compared the performance of these methods; for each algorithm, accuracy, precision, sensitivity, specificity, F1 score, and Area Under Curve (AUC) were calculated. RESULTS: 10,112 participants were recruited between 2014 and 2016, of whom 1246 had T2DM at baseline. 4566 (45%) participants were males, aged between 35 and 70 years. For males, age, sugar consumption, and history of hospitalization were the most weighted variables regarding their importance in screening for T2DM using the GBM model, respectively; these variables were sugar consumption, urine blood, and age for females. GBM outperformed other models for both males and females with AUC of 0.75 (0.69-0.82) and 0.76 (0.71-0.80), and F1 score of 0.33 (0.27-0.39) and 0.42 (0.38-0.46), respectively. GBM also showed a sensitivity of 0.24 (0.19-0.29) and a specificity of 0.98 (0.96-1.0) in males and a sensitivity of 0.38 (0.34-0.42) and specificity of 0.92 (0.89-0.95) in females. Notably, close performance characteristics were detected among other ML models. CONCLUSIONS: GBM model might achieve better performance in screening for T2DM in a south Iranian population.

Efficacy and safety of temozolomide-based regimens in advanced pancreatic neuroendocrine tumors: a systematic review and meta-analysis.

BACKGROUND: Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients. In this meta-analysis, we aimed to assess the outcome of temozolomide, alone or in combination with other anticancer medications in patients with advanced pNET. METHODS: Online databases of PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.gov were searched systematically for clinical trials that reported the efficacy and safety of temozolomide in patients with advanced pNET. Random-effect model was utilized to estimate pooled rates of outcomes based on Response Evaluation Criteria in Solid Tumors criteria, biochemical response, and adverse events (AEs). RESULTS: A total of 14 studies, providing details of 441 individuals with advanced pNET, were included. The quantitative analyses showed a pooled objective response rate (ORR) of 41.2% (95% confidence interval, CI, of 32.4%-50.6%), disease control rate (DCR) of 85.3% (95% CI of 74.9%-91.9%), and a more than 50% decrease from baseline chromogranin A levels of 44.9% (95% CI of 31.6%-49.0%). Regarding safety, the results showed that the pooled rates of nonserious AEs and serious AEs were 93.8% (95% CI of 88.3%-96.8%) and 23.7% (95% CI of 12.0%-41.5%), respectively. The main severe AEs encompassed hematological toxicities. CONCLUSIONS: In conclusion, our meta-analysis suggests that treatment with temozolomide, either as a monotherapy or in combination with other anticancer treatments might be an effective and relatively safe option for patients with advanced locally unresectable and metastatic pNET. However, additional clinical trials are required to further strengthen these findings. This study has been registered in PROSPERO (CRD42023409280).

The effect of mass media campaigns on oral health knowledge: A systematic review and meta-analysis.

OBJECTIVES: Knowledge and awareness gained from mass media can prepare people for lifestyle changes and impact their health and well-being. Considering the differences in the results of primary studies, we decided to conduct this study to evaluate the effect of mass media campaigns on oral health knowledge as a systematic meta-analysis and review. METHOD: The databases such as the Web of Sciences (ISI), Scopus, PubMed/Medline, and the Cochrane Library were searched systematically until February 2022. Data pooling was performed using a random effects model. The effect sizes were estimated as odds ratios (ORs) with their 95% confidence intervals (CIs). Additional analyses, including sensitivity, subgroup, and publication bias analyses, were also conducted. RESULTS: Our meta-analysis comprised a total number of seven articles. The pooled results indicated significant increases in oral health knowledge among included studies (OR = 1.64, 95% CI: 1.20-2.24, p < 0.001). In subgroup analyses, the effects of mass media campaigns on oral health knowledge remained significant for the studies with follow-up of less than 150 weeks (OR = 1.69, 95% CI: 1.49-1.91) and working-age populations (OR = 1.80, 95% CI: 1.40-2.32) compared to other categories. CONCLUSION: In general, this study showed that mass media campaigns may have positive effects on oral health knowledge, especially in the working-age population; it seems that for improving health knowledge among children, more initiatives are needed. Besides, the effects of these campaigns seem to be time-dependent and higher in shorter follow-up periods.

The Prevalence of Obstructive Sleep Apnea and Associated Symptoms among Patients with Sickle Cell Disease: A Systematic Review and Meta-analysis.

Previous studies have shown that patients with sickle cell disease (SCD) are at high risk for obstructive sleep apnea (OSA). In the current study, we aimed to systematically review the literature to address the prevalence of OSA and associated symptoms among patients with SCD. Electronic databases, including Web of Science, Scopus, PubMed, Google Scholar, and Embase were systematically searched to identify the relevant original articles on patients with SCD. Newcastle Ottawa scale was used for quality assessment. Data were pooled by using random effects models. Subgroup analyses were performed by age groups. Thirty-nine studies containing details of 299,358 patients with SCD were included. The pooled results showed that more than half of these patients had OSA with different severities. The prevalence rates of OSA among children with apnea hypopnea index (AHI) cutoffs of above 1, 1.5, and 5 were 51% (95% confidence interval (CI) 36-67%), 29% (95% CI 19-40%), and 18% (95% CI 14-23%), respectively. The prevalence of OSA among adults with AHI cutoff of 5 was 43% (95% CI 21-64%). The pooled rates of snoring, nocturnal enuresis, nocturnal desaturation, and daytime sleepiness were 55% (95% CI 42-69%), 37% (95% CI 33-41%), 49% (95% CI 26-72%), and 21% (95% CI 12-30%), respectively. Given the high prevalence of OSA in patients with SCD, probable greater burden of SCD complications, and irreversible consequences of OSA, screening for OSA symptoms and signs seems useful in these patients. By screening and identifying this heterogeneous disorder earlier, available treatment modalities can be individualized for each patient.

Endovascular therapy for acute stroke with a large infarct core: A systematic review and meta-analysis.

OBJECTIVE: In this meta-analysis, we aimed to investigate the efficacy and safety of endovascular treatment (EVT) for acute ischemic stroke (AIS) patients with large core infarct. METHODS: Three online databases of Web of Science, PubMed and Scopus were systematically searched. Original studies which evaluated AIS participants with large core infarction who underwent EVT were included. R statistical software was used for statistical analyses. Effect sizes were presented with odds ratios (ORs) with their 95% confidence intervals (CIs). The effect sizes were pooled using random effects modeling. RESULTS: Including 47 studies and 15,173 patients, this meta-analysis showed that compared with medical management (MM), EVT was significantly associated with decreased odds of mortality (0.67, 95% CI: 0.51-0.87) and increased odds of favorable outcomes, including a modified Rankin Scale of 0-3 (2.36, 95% CI: 1.69-3.291) and of 0-2 (3.54, 95% CI: 1.96-6.4) in 90 days and remarkable improvement in National Institutes of Health Stroke Scale within 48 h after the procedure (3.6, 95% CI:1.32-9.79). Besides, there was a higher chance of intracranial hemorrhage (ICH) development (1.88, 95% CI: 1.32-2.68) but not symptomatic ICH (1.34, 95% CI: 0.78-2.31) in those who underwent EVT. CONCLUSION: Our study suggests that EVT might be an effective and relatively safe treatment option for the treatment of AIS patients with large vessel occlusion who have large core infarcts, although more large-scale trials are needed to consolidate the results and to make inclusion criteria and the patient selection process clearer.

Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.

Background: Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue. Materials and Method: An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293). Results: The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected. Conclusion: In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.

Validity and reliability of the Persian version of modified motivated strategies for learning questionnaire: a methodological study among medical students.

BACKGROUND: Medical undergraduates need to improve their techniques for learning in the different settings of learning in clinical rotations. Reflective learning, in which a person can learn from their experiences, is among the most well-known learning skills. In this study, we aim to translate the newly developed modified form of the motivated strategies for learning questionnaire (MSLQ) to Persian and evaluate its reliability and validity among medical students. METHODS: This study was performed on medical students in clinical stages at the Shiraz University of Medical Science in 2022. The modified MSLQ questionnaire was used in this study which is a 32-item tool measuring different aspects of self-reflecting, including self-orientation, feedback-seeking, critical thinking, and self-regulation. This questionnaire was translated into Persian properly. Cronbach's alpha and confirmatory factor analysis were used to ascertain the reliability and validity of the tool. RESULTS: A total of 325 medical students consisting of 174 men and 151 women with an average age of 23.79 (± 2.21) were enrolled. Path diagrams of confirmatory factor analysis for both standardized regression coefficients and t-values and all the fitness indicators were in favor of the proper validation of the translated version. The overall Cronbach's alpha for the questionnaire was 0.9, and the value for each of four subscales was above 0.7. CONCLUSIONS: Our study showed that the Persian-translated version of the modified MSLQ is valid and reliable without taking too much time and effort to implement. We recommend that the developed tool be distributed to medical students from other Iran universities.

Early Morning Cortisol Level as a Predictive Factor for Long-Term Glucocorticoid Replacement After Pituitary Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: A reliable strategy for predicting long-term adrenal insufficiency after pituitary surgery can reduce the risk of glucocorticoid overexposure or missing patients with pituitary insufficiency. For this purpose, we aimed to assess the predictive value of early postoperative morning serum cortisol level for the detection of hypothalamic-pituitary-adrenal axis dysfunction in patients who underwent pituitary surgery. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-based systematic review was conducted to include articles investigating morning blood cortisol levels after pituitary surgery for lesions of the pituitary gland as a determinant for administration of long-term supplemental glucocorticoids. Bayesian statistics were used to pool the sensitivity and specificity rates. Sensitivity and specificity were also determined for each potential cortisol level on postoperative day (POD) 1 and POD 2. RESULTS: The study included 17 articles encompassing 1648 patients. Morning cortisol levels on POD 1 and POD 2 showed pooled sensitivity rates of 86.4% and 86.6% and pooled specificity rates of 73.1% and 78.2%, respectively, for predicting long-term glucocorticoid replacement after surgery. A cortisol level of 2.1 µg/dL showed the highest sensitivity rate (98.78%), and 22.5 µg/dL showed the highest specificity rate (72.5%) on POD 1. CONCLUSIONS: In this review and Bayesian meta-analysis, we found that postoperative serum cortisol measurement may have high accuracy in prediction of the long-term need for glucocorticoid administration in patients who underwent pituitary surgery.

The effects of chicory supplementation on liver enzymes and lipid profiles in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of clinical evidence.

BACKGROUND & AIMS: The beneficial effects of Cichorium intybus L., chicory, in patients with non-alcoholic fatty liver disease (NAFLD) are controversial. This review aimed to systematically summarize the evidence on the effects of chicory on liver function and lipid profile in patients with NAFLD. METHODS: Online databases of Scopus, Web of Science, PubMed, EMBASE, Cochrane Library, and grey literature were searched for relevant randomized clinical trials. Weighted mean differences (WMD) with 95% confidence intervals (CIs) were used as effect sizes and a random-effects model was used to pool the data. Besides, sensitivity analyses and publication bias analysis were performed. RESULTS: In total, five articles containing 197 patients with NAFLD were included. The study showed that chicory significantly decreased the levels of both aspartate transaminase (WMD: -7.07 U/L, 95%CI: -13.82 to -0.32) and alanine transaminase (WMD: -17.53 U/L, 95%CI: -32.64 to -2.42). However, no significant effects on alkaline phosphatase and gamma-glutamyl transferase levels and the components of the lipid profile were observed with the use of chicory. CONCLUSIONS: This meta-analysis showed that chicory supplementation may exert potential hepatoprotective effects in patients with NAFLD. However, for widespread recommendations, more studies with a higher number of patients and longer periods of intervention are mandatory.

Effects of l-arginine supplementation in patients with sickle cell disease: A systematic review and meta-analysis of clinical trials.

Background and Aims: Previous studies have shown that supplementation of some amino acids such as l-arginine or its precursors could exert beneficial effects in patients with sickle cell disease (SCD). The objective of this study is to systematically review the literature to assess the effect of arginine administration on the clinical and paraclinical parameters of patients with SCD. Methods: Four online databases of PubMed, Web of Sciences, Scopus, and Embase were selected for systematic search. Eligible studies were clinical trials that evaluated the effect of arginine usage in patients with SCD. Effects sizes were calculated using weighted mean difference (WMD) and Hedge's g and they were pooled using random-effects modeling with Hartung-Knapp adjustment. Additional analyses were also conducted. Results: Twelve studies containing detail of 399 patients with SCD were found to be eligible. The data synthesis showed that l-arginine significantly increased the level of NO metabolites (Hedge's g: 1.50, 0.48-1.82, I 2: 88%) and hemoglobin F (WMD: 1.69%, 0.86-2.52, I 2: 0%) and significantly decreased systolic blood pressure (WMD: -8.46 mmHg, -15.58 to -1.33, I 2: 53%) and aspartate transaminase (Hedge's g: -0.49, -0.73 to -0.26, I 2: 0%). However, there were no significant effects on hemoglobin, reticulocyte, malondialdehyde and diastolic blood pressure, and alanine transaminase. Conclusion: Our meta-analysis showed that l-arginine use for SCD could be beneficial, increase hemoglobin F and exert blood pressure-lowering and hepatoprotective properties. However, for a firm conclusion and widespread use of  l-arginine for these patients, more studies are needed.

Effect of deep brain stimulation on freezing of gait in patients with Parkinson's disease: a systematic review.

BACKGROUND AND OBJECTIVES: Freezing of gait (FOG) is a disabling gait disorder in patients with Parkinson's disease (PD), characterized by recurrent episodes of halting steps. Dopaminergic drugs are common treatments for PD and FOG; however, these drugs may worsen FOG. Deep brain stimulation (DBS) is another option used to treat selected patients. The device needs to be programmed at a specific frequency, amplitude, and pulse width to achieve optimum effects for each patient. This systematic review aimed to evaluate the efficacy of DBS for FOG and its correlation with programmed parameters and the location of the electrodes in the brain. MATERIALS AND METHODS: Data for this systematic review were gathered from five online databases: Medline (via PubMed), Scopus, Embase, Web of Science, and Cochrane Library (including both Cochrane Reviews and Cochrane Trials) with a broad search strategy. We included those articles that reported clinical trials and a specific measurement for FOG. RESULTS: This review included 13 studies of DBS that targeted the subthalamic nucleus (STN), substantia nigra (SNr), or pedunculopontine nucleus (PPN). Our analysis showed that low-frequency stimulation (LFS) was superior to high-frequency stimulation (HFS) for improving FOG. In the long term, the efficacy of both LFS and HFS decreased. The effect of amplitude was variable, and this parameter needed to be adjusted for each patient. Bilateral stimulation was better than unilateral stimulation. CONCLUSION: DBS is a promising choice for the treatment of severe FOG in patients with PD. Bilateral, low-frequency stimulation combined with medical therapy is associated with better responses, especially in the first 2 years of treatment. However, individualizing the DBS parameters should be considered to optimize treatment response.