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International Journal of Molecular... May 2024The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated... (Review)
Review
The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson's or Alzheimer's disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate transcriptional activity. The main characteristic shared by all patients is mild to severe developmental delay/intellectual disability. Moderate to severe disorder of the expressive and receptive language is present in at least 42%, while neuro-psychiatric issues were reported in 53% of patients. Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients, although probably underestimated because of its frequent onset in late adolescence-young adulthood. Finally, epilepsy was surprisingly present in 42% of patients, being drug-resistant in three of them. The age at onset varied widely, from five months to twenty-six years, as did the classification of epilepsy, which ranged from focal epilepsy to infantile spasms or Lennox-Gastaut syndrome. Accordingly, we propose that should be considered as a first-tier target gene for the genetic diagnosis of developmental and epileptic encephalopathy.
Topics: Humans; Epilepsy; Nuclear Receptor Subfamily 4, Group A, Member 2; Developmental Disabilities; Intellectual Disability
PubMed: 38791237
DOI: 10.3390/ijms25105198 -
BMC Infectious Diseases May 2024The burden of hepatitis E in Southeast Asia is substantial, influenced by its distinct socio-economic and environmental factors, as well as variations in healthcare... (Meta-Analysis)
Meta-Analysis
The burden of hepatitis E in Southeast Asia is substantial, influenced by its distinct socio-economic and environmental factors, as well as variations in healthcare systems. The aim of this study was to assess the pooled seroprevalence of hepatitis E across countries within the Southeast Asian region by the UN division.The study analyzed 66 papers across PubMed, Web of Science, and Scopus databases, encompassing data from of 44,850 individuals focusing on anti-HEV seroprevalence. The investigation spanned nine countries, excluding Brunei and East Timor due to lack of data. The pooled prevalence of anti-HEV IgG was determined to be 21.03%, with the highest prevalence observed in Myanmar (33.46%) and the lowest in Malaysia (5.93%). IgM prevalence was highest in Indonesia (12.43%) and lowest in Malaysia (0.91%). The study stratified populations into high-risk (farm workers, chronic patients) and low-risk groups (general population, blood donors, pregnant women, hospital patients). It revealed a higher IgG-28.9%, IgM-4.42% prevalence in the former group, while the latter group exhibited figures of 17.86% and 3.15%, respectively, indicating occupational and health-related vulnerabilities to HEV.A temporal analysis (1987-2023), indicated an upward trend in both IgG and IgM prevalence, suggesting an escalating HEV burden.These findings contribute to a better understanding of HEV seroprevalence in Southeast Asia, shedding light on important public health implications and suggesting directions for further research and intervention strategies.Key pointsResearch QuestionInvestigate the seroprevalence of hepatitis E virus (HEV) in Southeast Asian countries focusing on different patterns, timelines, and population cohorts.FindingsSporadic Transmission of IgG and IgM Prevalence:• Pooled anti-HEV IgG prevalence: 21.03%• Pooled anti-HEV IgM prevalence: 3.49%Seroprevalence among specific groups:High-risk group (farm workers and chronic patients):• anti-HEV IgG: 28.9%• anti-HEV IgM: 4.42%Low-risk group (general population, blood donors, pregnant women, hospital patients):• anti-HEV IgG: 17.86%• anti-HEV IgM: 3.15%Temporal Seroprevalence of HEV:Anti-HEV IgG prevalence increased over decades (1987-1999; 2000-2010; 2011-2023): 12.47%, 18.43%, 29.17% as an anti-HEV IgM prevalence: 1.92%, 2.44%, 5.27%ImportanceProvides a comprehensive overview of HEV seroprevalence in Southeast Asia.Highlights variation in seroprevalence among different population groups.Reveals increasing trend in HEV seroprevalence over the years.Distinguishes between sporadic and epidemic cases for a better understanding of transmission dynamics.
Topics: Hepatitis E; Humans; Seroepidemiologic Studies; Hepatitis E virus; Immunoglobulin M; Immunoglobulin G; Hepatitis Antibodies; Asia, Southeastern; Female; Prevalence; Risk Factors; Male; Pregnancy
PubMed: 38789918
DOI: 10.1186/s12879-024-09349-2 -
Journal of Dentistry Jul 2024The study answers the PECO question: "In adults with dental implants (P), do subjects suffering from type-2 diabetes or prediabetes (E) have worse peri-implant... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The study answers the PECO question: "In adults with dental implants (P), do subjects suffering from type-2 diabetes or prediabetes (E) have worse peri-implant conditions (O) than subjects without type-2 diabetes and prediabetes (C)?". Prediabetes (5.7-6.4 % HbA1c), and the different qualities of glycemic control in type-2 diabetes; well-controlled (>8 % HbA1c), and poorly controlled (>8 % HbA1c) individuals; were classified according to the recommendations of the American Diabetes Association.
DATA
Predefined search keys were used with search terms including: Dental implant, diabetes mellitus, glycemic control and HbA1c.
SOURCES
An electronic search in the MEDLINE, Embase, and Cochrane libraries were conducted without any filters or language restrictions. Additionally, manual search of the reference lists were carried out to identify all relevant articles.
STUDY SELECTION
Eligibility criteria were cohort, case-control and cross-sectional studies that answerd our PECO question with at least 1 year of follow-up. From a total of 2660 records, 35 articles (1761 individuals) were included in the analysis. Meta-analytic difference in means for crestal bone loss was 1.2 mm [95 % CI=0.4; 2.1] in patients with prediabetes, 1.8 mm [CI=1.0; 2.7] in poorly controlled patients, whereas 0.4 mm [CI=-0.3; 1.1] in well-controlled individuals. Meta-regression showed that 1 % increase in HbA1c increased crestal bone loss by 0.24 mm.
CONCLUSIONS
Within the limitations of the study, patients with poorly controlled type-2 diabetes or prediabetes may have worse peri-implant conditions compared to patients without diabetes and well-controlled type-2 diabetes. Well-controlled type-2 diabetes is not a risk indicator for peri-implant diseases.
CLINICAL SIGNIFICANCE
Clinicians should measure blood HbA1c levels when planning implant-supported restorations, thus patients with undiagnosed or poorly controlled type-2 diabetes can be identified, that allows for glycemic level adjustment prior to dental implant surgery, ensuring peri-implant health. PROTOCOL REGISTRATION NUMBER: (CRD42022375263).
Topics: Humans; Diabetes Mellitus, Type 2; Prediabetic State; Dental Implants; Glycated Hemoglobin; Risk Factors; Peri-Implantitis; Glycemic Control
PubMed: 38788918
DOI: 10.1016/j.jdent.2024.105094 -
Archives of Endocrinology and Metabolism May 2024Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We... (Comparative Study)
Comparative Study
Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: -1.46, 95% confidence interval [CI]: -1.76 to -1.17, < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.
Topics: Humans; Familial Hypophosphatemic Rickets; Antibodies, Monoclonal, Humanized; Fibroblast Growth Factor-23; Treatment Outcome; Calcitriol; Antibodies, Monoclonal; Phosphorus
PubMed: 38788147
DOI: 10.20945/2359-4292-2023-0242 -
Human Vaccines & Immunotherapeutics Dec 2024Solid cancer patients, compared to their healthy counterparts, are at a greater risk of contracting and suffering from severe complications and poorer prognosis after... (Meta-Analysis)
Meta-Analysis
Solid cancer patients, compared to their healthy counterparts, are at a greater risk of contracting and suffering from severe complications and poorer prognosis after COVID-19 infections. They also have different immune responses after doses of COVID-19 vaccination, but limited evidence is available to reveal the effectiveness and help to guide immunization programs for this subpopulation; MEDLINE, Embase, Web of Science, Cochrane Library databases, and clinicaltrials.gov were used to search literature. The pooled seroconversion rate was calculated using a random-effects model and reported with a 95% confidence interval (CI); The review includes 66 studies containing serological responses after COVID-19 vaccination in 13,050 solid cancer patients and 8550 healthy controls. The pooled seropositive rates after the first dose in patients with solid cancer and healthy controls are 55.2% (95% CI 45.9%-64.5% = 18) and 90.2% (95% CI 80.9%-96.6% = 13), respectively. The seropositive rates after the second dose in patients with solid cancer and healthy controls are 87.6% (95% CI 84.1%-90.7% = 50) and 98.9% (95% CI 97.6%-99.7% = 35), respectively. The seropositive rates after the third dose in patients with solid cancer and healthy controls are 91.4% (95% CI 85.4%-95.9% = 21) and 99.8% (95% CI 98.1%-100.0% = 4), respectively. Subgroup analysis finds that study sample size, timing of antibody testing, and vaccine type have influence on the results; Seroconversion rates after COVID-19 vaccination are significantly lower in patients with solid malignancies, especially after the first dose, then shrinking gradually after the following two vaccinations, indicating that subsequent doses or a booster dose should be considered for the effectiveness of this subpopulation.
Topics: Humans; Neoplasms; COVID-19 Vaccines; COVID-19; Antibodies, Viral; Seroconversion; SARS-CoV-2; Vaccination
PubMed: 38785118
DOI: 10.1080/21645515.2024.2357424 -
BMC Cancer May 2024Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN)...
BACKGROUND
Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN) guidelines and the European Society for Medical Oncology (ESMO) guidelines as the first-line (1 L) treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced/metastatic breast cancer (HR+/HER2- LABC/mBC). Although there are many treatment options, there is no clear standard of care for patients following 1 L CDK4/6i. Understanding the real-world effectiveness of subsequent therapies may help to identify an unmet need in this patient population. This systematic literature review qualitatively synthesized effectiveness and safety outcomes for treatments received in the real-world setting after 1 L CDK4/6i therapy in patients with HR+/ HER2- LABC/mBC.
METHODS
MEDLINE®, Embase, and Cochrane were searched using the Ovid® platform for real-world evidence studies published between 2015 and 2022. Grey literature was searched to identify relevant conference abstracts published from 2019 to 2022. The review was conducted in accordance with PRISMA guidelines (PROSPERO registration: CRD42023383914). Data were qualitatively synthesized and weighted average median real-world progression-free survival (rwPFS) was calculated for NCCN/ESMO-recommended post-1 L CDK4/6i treatment regimens.
RESULTS
Twenty records (9 full-text articles and 11 conference abstracts) encompassing 18 unique studies met the eligibility criteria and reported outcomes for second-line (2 L) treatments after 1 L CDK4/6i; no studies reported disaggregated outcomes in the third-line setting or beyond. Sixteen studies included NCCN/ESMO guideline-recommended treatments with the majority evaluating endocrine-based therapy; five studies on single-agent ET, six studies on mammalian target of rapamycin inhibitors (mTORi) ± ET, and three studies with a mix of ET and/or mTORi. Chemotherapy outcomes were reported in 11 studies. The most assessed outcome was median rwPFS; the weighted average median rwPFS was calculated as 3.9 months (3.3-6.0 months) for single-agent ET, 3.6 months (2.5-4.9 months) for mTORi ± ET, 3.7 months for a mix of ET and/or mTORi (3.0-4.0 months), and 6.1 months (3.7-9.7 months) for chemotherapy. Very few studies reported other effectiveness outcomes and only two studies reported safety outcomes. Most studies had heterogeneity in patient- and disease-related characteristics.
CONCLUSIONS
The real-world effectiveness of current 2 L treatments post-1 L CDK4/6i are suboptimal, highlighting an unmet need for this patient population.
Topics: Humans; Cyclin-Dependent Kinase 4; Breast Neoplasms; Receptor, ErbB-2; Cyclin-Dependent Kinase 6; Female; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Receptors, Estrogen; Receptors, Progesterone; Progression-Free Survival
PubMed: 38783218
DOI: 10.1186/s12885-024-12269-8 -
PLoS Neglected Tropical Diseases May 2024Toxoplasmosis is a serious endemic zoonotic disease caused by the protozoan parasite Toxoplasma gondii. Toxoplasma infection during pregnancy can result in congenital... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Toxoplasmosis is a serious endemic zoonotic disease caused by the protozoan parasite Toxoplasma gondii. Toxoplasma infection during pregnancy can result in congenital transmission and serious fetal and neonatal complications. This systematic review and meta-analysis aimed to assess the pooled seroprevalence of T. gondii infection and its determinants among pregnant women in African countries.
METHODS
All articles reporting the seroprevalence of toxoplasmosis among pregnant women in African countries and published from 2010 to 2023 were searched using various databases. The pooled prevalence of toxoplasmosis was calculated using a random-effect model. The variation between the included studies was assessed using a funnel plot and I2 heterogeneity statistics. To identify the sources of heterogeneity, sub-group analysis was further conducted by country, diagnostic method, and sub-African region. The association of prevalence rates with the socio-economic level and geoclimatic parameters was also explored.
RESULTS
In total, 29,383 pregnant women from 60 articles were included for analysis. The pooled T. gondii seroprevalence was 42.89% with high heterogeneity (I2 = 99.4%, P < 0.001). Sub-group analysis revealed variation by country (ranging from 2.62% in Namibia to 80.28% in Congo), diagnostic method used (from 8.66% in studies using a rapid diagnostic test to 55.69% in those using an agglutination test), and sub-African region (from 4.14% in regions of Southern Africa to 53.96 in Central Africa). Cat ownership (OR = 1.58) and the consumption of raw meat (OR = 1.50) and raw vegetables (OR = 1.48) had a statistically significant combined effect on T. gondii seroprevalence. No association was found between T. gondii prevalence and the level of income of the country or geoclimatic parameters.
CONCLUSION
The prevalence of toxoplasmosis infection among pregnant women in Africa is high, particularly in Central and Eastern Africa. The determinants of prevalence are multifactorial. Therefore, efforts should be made to increase the awareness of women concerning the risk factors for toxoplasmosis.
Topics: Humans; Female; Seroepidemiologic Studies; Pregnancy; Toxoplasmosis; Toxoplasma; Africa; Pregnancy Complications, Parasitic; Antibodies, Protozoan; Animals; Prevalence; Pregnant Women
PubMed: 38781272
DOI: 10.1371/journal.pntd.0012198 -
PloS One 2024This study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide meaningful guidance for clinical practice.
METHODS
A systematic retrieval of relevant studies on curcumin intervention in rats or mice hepatic fibrosis models was conducted, and the data were extracted. The outcome indicators included liver cell structure and function related indicators, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), ratio of albumin to globulin (A/G), total bilirubin (TBIL), bax protein, bcl-2 protein and index of liver, as well as the relevant indicators for evaluating the degree of hepatic fibrosis, such as hyaluronic acid (HA), laminin (LN), type I collagen (Collagen I), type III collagen (Collagen III), type III procollagen (PCIII), type III procollagen amino terminal peptide (PIIINP), type IV collagen (IV-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), α-Smooth muscle actin (α-SMA), hydroxyproline (HYP), platelet derived factor-BB (PDGF-BB), connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1), and oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px). These results were then analyzed by meta-analysis. Studies were evaluated for methodological quality using the syrcle's bias risk tool.
RESULTS
A total of 59 studies were included in the meta-analysis, and the results showed that curcumin can reduce the levels of ALT, AST, ALP, TBIL, bax protein, and index of liver in hepatic fibrosis models. It can also reduce HA, LN, Collagen I, Collagen III, PCIII, PIIINP, IV-C, TNF-α, α-SMA, HYP, PDGF-BB, CTGF, TGF-β1 and MDA, and increase the levels of ALB, A/G, SOD, and GSH-Px in the hepatic fibrosis models. However, the effects of curcumin on bcl-2 protein, IL-6 in hepatic fibrosis models and index of liver in mice were not statistically significant.
CONCLUSION
The analysis results indicate that curcumin can reduce liver cell apoptosis by maintaining the stability of liver cell membrane, inhibit the activation and proliferation of hepatic stellate cells by reducing inflammatory response, and alleviate tissue peroxidation damage by clearing oxygen free radicals.
Topics: Animals; Liver Cirrhosis; Curcumin; Mice; Rats; Disease Models, Animal; Oxidative Stress; Liver
PubMed: 38781262
DOI: 10.1371/journal.pone.0304176 -
BMC Cancer May 2024We provided an overview which evaluated the diagnostic performance of circulation EV biomarkers for CRC from PubMed, Medline, and Web of Science until 21 August... (Meta-Analysis)
Meta-Analysis
We provided an overview which evaluated the diagnostic performance of circulation EV biomarkers for CRC from PubMed, Medline, and Web of Science until 21 August 2022.Weidentified 48 studies that involved 7727 participants and evaluated 162 plasma/serum individual EV biomarkers including 117 RNAs and 45 proteins, as well as 45 EV biomarker panels for CRC detection. 12 studies evaluated the diagnostic performance of EV biomarkers for early CRC. The summarized sensitivity, specificity, and AUC value of individual EV RNAs and EV RNA panels were 76%, 75%, 0.87 and 82%, 79% and 0.90, respectively. Meanwhile, those of individual EV proteins and EV protein panels were 85%, 84%, 0.92 and 87%, 83%, 0.92, respectively. These results indicated that EV biomarker panels revealed superior diagnostic performance than the corresponding individual biomarkers. In early CRC, EV biomarkers showed available diagnostic value with the sensitivity, specificity, and AUC value of 80%, 75%, and 0.89.In subgroup analyses, EV miRNAs and LncRNAs held similar diagnostic value with the sensitivity, specificity and AUC value of 75%, 78%, 0.90 and 79%, 72%, 0.83, which was highly consistent with the whole EV RNAs. Significantly, the diagnostic values of EV miRNAs in plasma were marginally higher than those based on serum. In detail, the sensitivity, specificity, and AUC values were 79%, 81%, and 0.92 in plasma, as well as 74%, 77%, and 0.88 in serum, respectively. Therefore, circulation EV biomarkers could be considered as a promising biomarker for the early detection of CRC.
Topics: Humans; Colorectal Neoplasms; Biomarkers, Tumor; Extracellular Vesicles; Early Detection of Cancer; MicroRNAs; Sensitivity and Specificity; RNA, Long Noncoding
PubMed: 38778252
DOI: 10.1186/s12885-024-12312-8 -
Clinical Nutrition ESPEN Jun 2024Colorectal cancer (CRC) is the third most common malignancy in developed countries. Therefore, omega-3 fatty acids (O3FAs) have been suggested as a beneficial... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Colorectal cancer (CRC) is the third most common malignancy in developed countries. Therefore, omega-3 fatty acids (O3FAs) have been suggested as a beneficial complementary treatment due to their ability to regulate inflammatory responses and improve nutrition levels.This study aimed to evaluate the effects of O3FAs as a complementary treatment for inflammation, nutrition levels, post-operative infectious complications, and enhancement of recovery in CRC patients.
METHODS
The literature search was carried out through three databases. The outcomes of interest were assessed by measuring pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and CRP levels, serum albumin levels for nutrition assessment, post-operative infectious complications, and length of stay for recovery evaluation. Quality appraisal and meta-analysis were performed using RoB 2.0 and RevMan 5.4, respectively.
RESULTS
The result showed that O3FAs significantly reduced IL-6, CRP, and TNF-α, but did not affect IL-1β. Furthermore, the variable slightly increased serum albumin levels and the supplementation led to a decrease in post-operative infectious complications and shortened hospital stays.
CONCLUSION
O3FAs as a complementary treatment provided advantages for CRC patients, Further clinical trials and experiments should also be made emphasizing the impact and clinical implementation of O3FA in the nutritional status of CRC patients.
Topics: Humans; Fatty Acids, Omega-3; Colorectal Neoplasms; Nutritional Status; Dietary Supplements; C-Reactive Protein; Complementary Therapies; Inflammation; Postoperative Complications; Cytokines
PubMed: 38777451
DOI: 10.1016/j.clnesp.2024.04.002