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Neurobiology of Disease Jul 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial... (Meta-Analysis)
Meta-Analysis
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p < 0.01) in the prevalence of lactate (17%), pyruvate (41%), alanine (15%) and creatine kinase (9%) were found in ASD. Individuals with ASD had significant differences (all p < 0.01) with moderate to large effect sizes (Cohen's d' ≥ 0.6) compared to controls in mean pyruvate, lactate-to-pyruvate ratio, ATP, and creatine kinase. Some studies found abnormal TCA cycle metabolites associated with ASD. Thirteen controlled studies reported mitochondrial DNA (mtDNA) deletions or variations in the ASD group in blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, and brain. Meta-analyses discovered significant differences (p < 0.01) in copy number of mtDNA overall and in ND1, ND4 and CytB genes. Four studies linked specific mtDNA haplogroups to ASD. A series of studies found a subgroup of ASD with elevated mitochondrial respiration which was associated with increased sensitivity of the mitochondria to physiological stressors and neurodevelopmental regression. Lactate, pyruvate, lactate-to-pyruvate ratio, carnitine, and acyl-carnitines were associated with clinical features such as delays in language, social interaction, cognition, motor skills, and with repetitive behaviors and gastrointestinal symptoms, although not all studies found an association. Lactate, carnitine, acyl-carnitines, ATP, CoQ10, as well as mtDNA variants, heteroplasmy, haplogroups and copy number were associated with ASD severity. Variability was found across biomarker studies primarily due to differences in collection and processing techniques as well as the intrinsic heterogeneity of the ASD population. Several studies reported alterations in mitochondrial metabolism in mothers of children with ASD and in neonates who develop ASD. Treatments targeting mitochondria, particularly carnitine and ubiquinol, appear beneficial in ASD. The link between mitochondrial dysfunction in ASD and common physiological abnormalities in individuals with ASD including gastrointestinal disorders, oxidative stress, and immune dysfunction is outlined. Several subtypes of mitochondrial dysfunction in ASD are discussed, including one related to neurodevelopmental regression, another related to alterations in microbiome metabolites, and another related to elevations in acyl-carnitines. Mechanisms linking abnormal mitochondrial function with alterations in prenatal brain development and postnatal brain function are outlined. Given the multisystem complexity of some individuals with ASD, this review presents evidence for the mitochondria being central to ASD by contributing to abnormalities in brain development, cognition, and comorbidities such as immune and gastrointestinal dysfunction as well as neurodevelopmental regression. A diagnostic approach to identify mitochondrial dysfunction in ASD is outlined. From this evidence, it is clear that many individuals with ASD have alterations in mitochondrial function which may need to be addressed in order to achieve optimal clinical outcomes. The fact that alterations in mitochondrial metabolism may be found during pregnancy and early in the life of individuals who eventually develop ASD provides promise for early life predictive biomarkers of ASD. Further studies may improve the understanding of the role of the mitochondria in ASD by better defining subgroups and understanding the molecular mechanisms driving some of the unique changes found in mitochondrial function in those with ASD.
Topics: Humans; Autism Spectrum Disorder; Biomarkers; DNA, Mitochondrial; Mitochondria; Mitochondrial Diseases
PubMed: 38703861
DOI: 10.1016/j.nbd.2024.106520 -
JNCI Cancer Spectrum Apr 2024Patients with head and neck cancer present particularly considerable levels of emotional distress. However, the actual rates of clinically relevant mental health... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with head and neck cancer present particularly considerable levels of emotional distress. However, the actual rates of clinically relevant mental health symptoms and disorders among this population remain unknown.
METHODS
A Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analyses of Observational Studies in Epidemiology-compliant systematic review and quantitative random-effects meta-analysis was performed to determine suicide incidence and the prevalence of depression, anxiety, distress, posttraumatic stress, and insomnia in this population. MEDLINE, Web of Science, Cochrane Central Register, KCI Korean Journal database, SciELO, Russian Science Citation Index, and Ovid-PsycINFO databases were searched from database inception to August 1, 2023 (PROSPERO: CRD42023441432). Subgroup analyses and meta-regressions were performed to investigate the effect of clinical, therapeutical, and methodological factors.
RESULTS
A total of 208 studies (n = 654 413; median age = 60.7 years; 25.5% women) were identified. Among the patients, 19.5% reported depressive symptoms (95% confidence interval [CI] = 17% to 21%), 17.8% anxiety symptoms (95% CI = 14% to 21%), 34.3% distress (95% CI = 29% to 39%), 17.7% posttraumatic symptoms (95% CI = 6% to 41%), and 43.8% insomnia symptoms (95% CI = 35% to 52%). Diagnostic criteria assessments revealed lower prevalence of disorders: 10.3% depression (95% CI = 7% to 13%), 5.6% anxiety (95% CI = 2% to 10%), 9.6% insomnia (95% CI = 1% to 40%), and 1% posttraumatic stress (95% CI = 0% to 84.5%). Suicide pooled incidence was 161.16 per 100 000 individuals per year (95% CI = 82 to 239). Meta-regressions found a statistically significant higher prevalence of anxiety in patients undergoing primary chemoradiation compared with surgery and increased distress in smokers and advanced tumor staging. European samples exhibited lower prevalence of distress.
CONCLUSIONS
Patients with head and neck cancer presented notable prevalence of mental health concerns in all domains. Suicide remains a highly relevant concern. The prevalence of criteria-meeting disorders is significantly lower than clinically relevant symptoms. Investigating the effectiveness of targeted assessments for disorders in highly symptomatic patients is essential.
Topics: Humans; Head and Neck Neoplasms; Depression; Anxiety; Stress Disorders, Post-Traumatic; Mental Health; Sleep Initiation and Maintenance Disorders; Suicide; Female; Male; Prevalence; Middle Aged; Psychological Distress; Incidence; Aged
PubMed: 38702757
DOI: 10.1093/jncics/pkae031 -
Journal of Current Ophthalmology 2023To look for causative genetic mutations in a series of Iranian families with strabismus. In addition, we systematically reviewed all the published articles regarding the... (Review)
Review
Role of Abelson Helper Integration Site 1, Nebulin, and Paired Box 3 Genes in the Development of Nonsyndromic Strabismus in a Series of Iranian Families: Sequence Analysis and Systematic Review of the Genetics of Nonsyndromic Strabismus.
PURPOSE
To look for causative genetic mutations in a series of Iranian families with strabismus. In addition, we systematically reviewed all the published articles regarding the role of genetic variations in primary and nonsyndromic comitant strabismus.
METHODS
Four families with a history of multiple cases of primary and nonsyndromic comitant strabismus were enrolled in this study. Polymerase chain reaction and Sanger sequencing of exons 23, 11, and 3 of the Abelson helper integration site 1 (), nebulin (), and paired box 3 () genes were performed, respectively. One offspring of a consanguineous marriage underwent whole-exome sequencing (WES) to look for possible causative variants. To conduct a systematic review, we thoroughly searched PubMed, Scopus, and ISI Web of Knowledge extracting relevant publications, released by April 2021.
RESULTS
We examined four Iranian strabismus pedigrees with multiple affected offspring in different generations. Among these 17 participants, 10 family members had strabismus and 7 were healthy. Sanger sequencing did not reveal a causative mutation. Therefore, to further investigate, one affected offspring was chosen for WES. The WES study demonstrated two possible variants in and genes. These genetic variants showed high allele frequency in our population and are thought to be polymorphisms in our series of Iranian families.
CONCLUSIONS
We demonstrated that mutations in , , and genes were not common in a series of Iranian patients with familial strabismus. Moreover, by performing WES, we revealed that two variants of uncertain significance as possible causative variants for strabismus are not related to this disease in our population.
PubMed: 38681684
DOI: 10.4103/joco.joco_53_22 -
Psychoneuroendocrinology Aug 2024The placenta acts as a buffer to regulate the degree of fetal exposure to maternal cortisol through the 11-Beta Hydroxysteroid Dehydrogenase isoenzyme type 2 (11-β... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The placenta acts as a buffer to regulate the degree of fetal exposure to maternal cortisol through the 11-Beta Hydroxysteroid Dehydrogenase isoenzyme type 2 (11-β HSD2) enzyme. We conducted a systematic review and meta-analysis to assess the effect of prenatal psychological distress (PPD) on placental 11-β HSD2 gene expression and explore the related mechanistic pathways involved in fetal neurodevelopment.
METHODS
We searched PubMed, Embase, Scopus, APA PsycInfo®, and ProQuest Dissertations for observational studies assessing the association between PPD and 11-β HSD2 expression in human placentas. Adjusted regression coefficients (β) and corresponding 95% confidence intervals (CIs) were pooled based on three contextual PPD exposure groups: prenatal depression, anxiety symptoms, and perceived stress.
RESULTS
Of 3159 retrieved records, sixteen longitudinal studies involving 1869 participants across seven countries were included. Overall, exposure to PPD disorders showed weak negative associations with the placental 11-β HSD2 gene expression as follows: prenatal depression (β -0.01, 95% CI 0.05-0.02, I2=0%), anxiety symptoms (β -0.02, 95% CI 0.06-0.01, I2=0%), and perceived stress (β -0.01 95% CI 0.06-0.04, I2=62.8%). Third-trimester PPD exposure was more frequently associated with lower placental 11-β HSD2 levels. PPD and placental 11-β HSD2 were associated with changes in cortisol reactivity and the development of adverse health outcomes in mothers and children. Female-offspring were more vulnerable to PPD exposures.
CONCLUSION
The study presents evidence of a modest role of prenatal psychological distress in regulating placental 11-β HSD2 gene expression. Future prospective cohorts utilizing larger sample sizes or advanced statistical methods to enhance the detection of small effect sizes should be planned. Additionally, controlling for key predictors such as the mother's ethnicity, trimester of PPD exposure, mode of delivery, and infant sex is crucial for valid exploration of PPD effects on fetal programming.
Topics: Humans; Pregnancy; 11-beta-Hydroxysteroid Dehydrogenase Type 2; Female; Placenta; Stress, Psychological; Pregnancy Complications; Psychological Distress; Depression; Gene Expression; Anxiety; Hydrocortisone; Prenatal Exposure Delayed Effects
PubMed: 38677195
DOI: 10.1016/j.psyneuen.2024.107060 -
Biomedicines Apr 2024The aim of this systematic review is to assess the power of circulating miRNAs as biomarkers as a diagnostic tool in endometriosis. In endometriosis-suspected women with... (Review)
Review
The aim of this systematic review is to assess the power of circulating miRNAs as biomarkers as a diagnostic tool in endometriosis. In endometriosis-suspected women with uncertain imaging, the only way to confirm or exclude endometriosis with certainty is currently laparoscopy. This creates a need for non-invasive diagnostics. We searched the literature through the PubMed database using the Mesh terms 'endometriosis' and 'miRNAs'. Some, but limited, overlap was found between the 32 articles included, with a total of 20 miRNAs reported as dysregulated in endometriosis in two or more studies. MiR-17-5p was reported as dysregulated in six studies, followed by miR-451a and let-7b-5p in four studies and miR-20a-5p, miR-143-3p, miR-199a-5p and miR-3613-5p in three studies. Furthermore, a possible impact of the menstrual phase on miRNA expression was noted in five studies, while no influence of hormonal intake was observed in any included study. The modest reproducibility between studies may be attributable to biological variability as well as to the lack of universal protocols, resulting in pre- and analytical variability. Despite the identification of several suitable candidate biomarkers among the miRNAs, the need for high-quality studies with larger and well-defined population cohorts and the use of standardized protocols lingers.
PubMed: 38672242
DOI: 10.3390/biomedicines12040888 -
Epilepsy & Behavior : E&B Jun 2024To estimate the prevalence of epilepsy and febrile seizures and their association with genotype, i.e., 15q11-q13 deletions, uniparental chromosome 15 disomy (UPD) and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the prevalence of epilepsy and febrile seizures and their association with genotype, i.e., 15q11-q13 deletions, uniparental chromosome 15 disomy (UPD) and other mutations, in the population with Prader-Willi syndrome (PWS).
METHODS
A systematic search of Medline, Scopus, Web of Science and the Cochrane Library was conducted. Studies estimating the prevalence of seizures, epilepsy and febrile seizures in the PWS population were included. Meta-analyses of the prevalence of epilepsy and febrile seizures and their association with genotype using the prevalence ratio (PR) were performed.
RESULTS
Fifteen studies were included. The prevalence of epilepsy was 0.11 (0.07, 0.15), similar to the prevalence of febrile seizures, with a prevalence of 0.09 (0.05, 0.13). The comparison "deletion vs. UPD" had a PR of 2.03 (0.90, 4.57) and 3.76 (1.54, 9.18) for epilepsy and febrile seizures.
CONCLUSIONS
The prevalence of seizure disorders in PWS is higher than in the general population. In addition, deletions in 15q11-q13 may be associated with a higher risk of seizure disorders. Therefore, active screening for seizure disorders in PWS should improve the lives of these people. In addition, genotype could be used to stratify risk, even for epilepsy, although more studies or larger sample sizes are needed.
Topics: Humans; Prader-Willi Syndrome; Epilepsy; Prevalence; Genotype; Chromosomes, Human, Pair 15
PubMed: 38663143
DOI: 10.1016/j.yebeh.2024.109803 -
International Journal of Gynecological... Jun 2024Circulating tumor DNA (ctDNA) is emerging as a potential prognostic biomarker in multiple tumor types. However, despite the many studies available on small series of... (Meta-Analysis)
Meta-Analysis
Circulating tumor DNA as a biomarker for predicting progression-free survival and overall survival in patients with epithelial ovarian cancer: a systematic review and meta-analysis.
OBJECTIVES
Circulating tumor DNA (ctDNA) is emerging as a potential prognostic biomarker in multiple tumor types. However, despite the many studies available on small series of patients with ovarian cancer, a recent systematic review and meta-analysis is lacking. The objective of this study was to determine the association of ctDNA with progression-free-survival and overall survival in patients with epithelial ovarian cancer.
METHODS
An electronic search was conducted using PubMed (MEDLINE), Embase, CENTRAL (Cochrane Library), and CINAHL-Complete from January 2000 to September 15, 2023. To be included in the analysis the studies had to meet the following pre-specified inclusion criteria: (1) evaluable ctDNA; (2) progression-free-survival and overall survival reported as hazard ratio (HR); and (3) the patient population had epithelial ovarian cancer at the time of ctDNA detection. We evaluated the association of ctDNA with progression-free survival and overall survival. Secondary outcomes focused on sub-group analysis of genomic alterations and international Federation of Gynecology and Obstetrics (FIGO) stage.
RESULTS
A total of 26 studies reporting on 1696 patients with epithelial ovarian cancer were included. The overall concordance rate between plasma-based and tissue-based analyses was approximately 62%. We found that a high level of ctDNA in epithelial ovarian cancer was associated with worse progression-free survival (HR 5.31, 95% CI 2.14 to 13.17, p<0.001) and overall survival (HR 2.98, 95% CI 1.86 to 4.76, p<0.0001). The sub-group analysis showed a greater than threefold increase in the risk of relapse in patients with positive HOXA9 meth-ctDNA (HR 3.84, 95% CI 1.57 to 9.41, p=0.003).
CONCLUSIONS
ctDNA was significantly associated with worse progression-free survival and overall survival in patients with epithelial ovarian cancer. Further prospective studies are needed.
PROSPERO REGISTRATION NUMBER
CRD42023469390.
Topics: Humans; Female; Carcinoma, Ovarian Epithelial; Circulating Tumor DNA; Ovarian Neoplasms; Progression-Free Survival; Biomarkers, Tumor
PubMed: 38658022
DOI: 10.1136/ijgc-2024-005313 -
Journal of Medical Internet Research Apr 2024Telemonitoring patients with cardiac implantable electronic devices (CIEDs) can improve their care management. However, the results of cost-effectiveness studies are... (Review)
Review
BACKGROUND
Telemonitoring patients with cardiac implantable electronic devices (CIEDs) can improve their care management. However, the results of cost-effectiveness studies are heterogeneous. Therefore, it is still a matter of debate whether telemonitoring is worth the investment.
OBJECTIVE
This systematic review aims to investigate the cost-effectiveness of telemonitoring patients with CIEDs, focusing on its key drivers, and the impact of the varying perspectives.
METHODS
A systematic review was performed in PubMed, Web of Science, Embase, and EconLit. The search was completed on July 7, 2022. Studies were included if they fulfilled the following criteria: patients had a CIED, comparison with standard care, and inclusion of health economic evaluations (eg, cost-effectiveness analyses and cost-utility analyses). Only complete and peer-reviewed studies were included, and no year limits were applied. The exclusion criteria included studies with partial economic evaluations, systematic reviews or reports, and studies without standard care as a control group. Besides general study characteristics, the following outcome measures were extracted: impact on total cost or income, cost or income drivers, cost or income drivers per patient, cost or income drivers as a percentage of the total cost impact, incremental cost-effectiveness ratios, or cost-utility ratios. Quality was assessed using the Consensus Health Economic Criteria checklist.
RESULTS
Overall, 15 cost-effectiveness analyses were included. All studies were performed in Western countries, mainly Europe, and had primarily a male participant population. Of the 15 studies, 3 (20%) calculated the incremental cost-effectiveness ratio, 1 (7%) the cost-utility ratio, and 11 (73%) the health and cost impact of telemonitoring. In total, 73% (11/15) of the studies indicated that telemonitoring of patients with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy ICDs was cost-effective and cost-saving, both from a health care and patient perspective. Cost-effectiveness results for telemonitoring of patients with pacemakers were inconclusive. The key drivers for cost reduction from a health care perspective were hospitalizations and scheduled in-office visits. Hospitalization costs were reduced by up to US $912 per patient per year. Scheduled in-office visits included up to 61% of the total cost reduction. Key drivers for cost reduction from a patient perspective were loss of income, cost for scheduled in-office visits and transport. Finally, of the 15 studies, 8 (52%) reported improved quality of life, with statistically significance in only 1 (13%) study (P=.03).
CONCLUSIONS
From a health care and patient perspective, telemonitoring of patients with an ICD or a cardiac resynchronization therapy ICD is a cost-effective and cost-saving alternative to standard care. Inconclusive results were found for patients with pacemakers. However, telemonitoring can lead to a decrease in providers' income, mainly due to a lack of reimbursement. Introducing appropriate reimbursement could make telemonitoring sustainable for providers while still being cost-effective from a health care payer perspective.
TRIAL REGISTRATION
PROSPERO CRD42022322334; https://tinyurl.com/puunapdr.
Topics: Humans; Male; Cost-Benefit Analysis; Quality of Life; Defibrillators, Implantable; Cardiac Resynchronization Therapy; Europe
PubMed: 38640471
DOI: 10.2196/47616 -
Journal of Cellular and Molecular... Apr 2024Interleukin-6 (IL-6), a pivotal pro-inflammatory cytokine, is closely linked to vascular wall thickening and atherosclerotic lesion. Since serum IL-6 levels are largely... (Meta-Analysis)
Meta-Analysis
Interleukin-6 (IL-6), a pivotal pro-inflammatory cytokine, is closely linked to vascular wall thickening and atherosclerotic lesion. Since serum IL-6 levels are largely determined by the genetic variant in IL-6, this study was conducted to investigate whether the IL-6 variant impacts cardiometabolic profile and the risk of premature coronary artery disease (PCAD). PubMed, Cochrane Library, Central, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ClinicalTrials.gov were searched from May 13, 2022 to June 28, 2023. In total, 40 studies (26,543 individuals) were included for the analysis. The rs1800795 (a function variant in the IL-6 gene) C allele was linked to higher levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), fasting plasma glucose (FPG), body mass index (BMI), and waist circumference (WC), and a lower levels of high-density lipoprotein cholesterol (HDL-C). However, no significant association was observed of rs1800795 with triglycerides (TG), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Interestingly, a significant association was detected between rs1800795 and PCAD. Subgroup analyses indicted that the impacts of rs1800795 on cardiometabolic risk factors were significant in Caucasians but stronger in obese patients. In contrast, the impact of rs1800795 on PCAD was significant in brown race population. In summary, rs1800795 had a slight but significant impact on cardiometabolic risk factors and PCAD. IL-6 inhibition with ziltivekimab or canakinumab may benefit high-risk populations (e.g. brown race population, Caucasians, obese patients, etc.) with rs1800795 to prevent PCAD.
Topics: Humans; Cardiovascular Diseases; Cholesterol, HDL; Coronary Artery Disease; Cytokines; Interleukin-6; Obesity; Risk Factors; Triglycerides
PubMed: 38634217
DOI: 10.1111/jcmm.18311 -
International Journal of Surgery... Apr 2024Migraine affects approximately 14-15% of the global population, contributing to nearly 5% of the world's health burden. When drug treatments prove ineffective for...
BACKGROUND
Migraine affects approximately 14-15% of the global population, contributing to nearly 5% of the world's health burden. When drug treatments prove ineffective for intractable migraines, highly specific surgical interventions emerge as potential solutions. We aimed to analyze surgical approaches for these refractory or intractable migraines through a systematic review and meta-analysis.
METHODS
We conducted a literature search across databases such as PubMed, Scopus, Web of Science, and Embase, focusing on studies related to migraines and surgical outcomes. We considered clinical trials or observational studies that included any surgical intervention for refractory or intractable migraines, emphasizing key outcomes such as reductions in migraine intensity, Migraine Disability Assessment scores (MIDAS), and 50% Migraine Headache Index (MHI) reduction rates. Statistical analyses were performed using R version 4.3.
RESULTS
Eleven studies were included in the systematic review. A meta-analysis of four studies involving overall 95 patients showed a significant reduction in mean migraine intensity scores using ONS (-2.27, 95% CI: -3.92 to -0.63, P=0.021). Three studies with 85 patients showed an average MIDAS score reduction of -52.3, though this was not statistically significant (95% CI: -136.85 to 32.19, P=0.116). Two additional studies corroborated these reductions in MIDAS scores. Nerve decompression surgery showed a substantial decrease in the average migraine intensity (from 8.31 down to 4.06). Median MIDAS score dropped from 57 to 20. Two studies indicated a success rate of 40% and 82%, respectively, in achieving a 50% reduction in the Migraine MHI through nerve decompression. Findings from two studies suggest that septorhinoplasty and sinus surgery effectively decrease migraine intensity scores.
CONCLUSION
The existing evidence emphasizes the potential advantages of surgical interventions as a promising approach to managing intractable or refractory migraines. However, robust and comprehensive research is crucial to refine and solidify the efficacy of these surgical methods, aiming for widespread benefits for patients, considering cost-effectiveness factors.
PubMed: 38626410
DOI: 10.1097/JS9.0000000000001480