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Cancer Medicine May 2024People with intellectual disabilities (ID) face barriers in cancer care contributing to poorer oncological outcomes. Yet, understanding cancer risks in the ID population... (Review)
Review
BACKGROUND
People with intellectual disabilities (ID) face barriers in cancer care contributing to poorer oncological outcomes. Yet, understanding cancer risks in the ID population remains incomplete.
AIM
To provide an overview of cancer incidence and cancer risk assessments in the entire ID population as well as within ID-related disorders.
METHODS
This systematic review examined cancer risk in the entire ID population and ID-related disorders. We systematically searched PubMed (MEDLINE) and EMBASE for literature from January 1, 2000 to July 15, 2022 using a search strategy combining terms related to cancer, incidence, and ID.
RESULTS
We found 55 articles assessing cancer risks in the ID population at large groups or in subgroups with ID-related syndromes, indicating that overall cancer risk in the ID population is lower or comparable with that of the general population, while specific disorders (e.g., Down's syndrome) and certain genetic mutations may elevate the risk for particular cancers.
DISCUSSION
The heterogeneity within the ID population challenges precise cancer risk assessment at the population level. Nonetheless, within certain subgroups, such as individuals with specific ID-related disorders or certain genetic mutations, a more distinct pattern of varying cancer risks compared to the general population becomes apparent.
CONCLUSION
More awareness, and personalized approach in cancer screening within the ID population is necessary.
Topics: Humans; Intellectual Disability; Neoplasms; Risk Assessment; Incidence; Risk Factors; Early Detection of Cancer
PubMed: 38686623
DOI: 10.1002/cam4.7210 -
Journal of Integrative Neuroscience Apr 2024Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in...
BACKGROUND
Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in MNDs, especially in conditions such as amyotrophic lateral sclerosis (ALS), and its interaction with frontotemporal dementia (FTD), has garnered increasing research interest. This systematic review analyzed magnetic resonance imaging (MRI) studies that focused on thalamic alterations in MNDs to understand the significance of these changes and their correlation with clinical outcomes.
METHODS
Following PRISMA 2020 guidelines, the PubMed and Scopus databases were searched from inception to June 2023 for studies related to MRI findings in the thalamus of patients with MNDs. Eligible studies included adult patients diagnosed with ALS or other forms of MND who underwent brain MRI, with outcomes related to thalamic alterations. Studies were evaluated for risk of bias using the Newcastle-Ottawa scale.
RESULTS
A total of 52 studies (including 3009 MND patients and 2181 healthy controls) used various MRI techniques, including volumetric analysis, diffusion tensor imaging, and functional MRI, to measure thalamic volume, connectivity, and other alterations. This review confirmed significant thalamic changes in MNDs, such as atrophy and microstructural degradation, which are associated with disease severity, progression, and functional disability. Thalamic involvement varies across different MND subtypes and is influenced by the presence of cognitive impairment and mutations in genes including chromosome 9 open reading frame 72 (). The synthesis of findings across studies indicates that thalamic pathology is a prevalent early biomarker of MNDs that contributes to motor and cognitive deficits. The thalamus is a promising target for monitoring as its dysfunction underpins a variety of clinical symptoms in MNDs.
CONCLUSIONS
Thalamic alterations provide valuable insights into the pathophysiology and progression of MNDs. Multimodal MRI techniques are potent tools for detecting dynamic thalamic changes, indicating structural integrity, connectivity disruption, and metabolic activity.
Topics: Humans; Thalamus; Motor Neuron Disease; Magnetic Resonance Imaging; Amyotrophic Lateral Sclerosis
PubMed: 38682227
DOI: 10.31083/j.jin2304077 -
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 -
Cancer Treatment Reviews Jun 2024Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their... (Review)
Review
BACKGROUND
Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their genome and transcriptome but also in the composition of their tumor immune microenvironment. The microsatellite instable (MSI) and Epstein-Barr virus (EBV) positive GC subtypes show clear clinical benefits from immune checkpoint blockade, likely due to a neoantigen-driven and virus-driven antitumor immune response and high expression of immune checkpoint molecule PD-L1. However, even within these subtypes response to checkpoint inhibition is variable, which is potentially related to heterogeneity in the tumor immune microenvironment (TIME) and expression of co-inhibitory molecules. We conducted a systematic review to outline the current knowledge about the immunological features on the TIME of MSI and EBV + GCs.
METHODS
A systematic search was performed in PubMed, EMBASE and Cochrane Library. All articles from the year 1990 and onwards addressing immune features of gastric adenocarcinoma were reviewed and included based on predefined in- and exclusion criteria.
RESULTS
In total 5962 records were screened, of which 139 were included that reported immunological data on molecular GC subtypes. MSI and EBV + GCs were reported to have a more inflamed TIME compared to non-MSI and EBV- GC subtypes. Compared to microsatellite stable (MSS) tumors, MSI tumors were characterized by higher numbers of CD8 + and FoxP3 + T cells, and tumor infiltrating pro- and anti-inflammatory macrophages. HLA-deficiency was most common in MSI tumors compared to other molecular GC subtypes and associated with lower T and B cell infiltrates compared to HLA-proficient tumors. EBV + was associated with a high number of CD8 + T cells, Tregs, NK cells and macrophages. Expression of PD-L1, CTLA-4, Granzyme A and B, Perforin and interferon-gamma was enriched in EBV + tumors. Overall, MSI tumors harbored a more heterogeneous TIME in terms of immune cell composition and immune checkpoints compared to the EBV + tumors.
DISCUSSION AND CONCLUSION
MSI and EBV + GCs are highly Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration.; 2019pro-inflammatory immune cell populations. Although studies on the direct comparison of EBV + and MSI tumors are limited, EBV + tumors show less intra-subgroup heterogeneity compared to MSI tumors. More studies are needed to identify how Intra-subgroup heterogeneity impacts response to immunotherapy efficacy.
Topics: Humans; Stomach Neoplasms; Tumor Microenvironment; Epstein-Barr Virus Infections; DNA Mismatch Repair; Herpesvirus 4, Human; Microsatellite Instability
PubMed: 38669788
DOI: 10.1016/j.ctrv.2024.102737 -
Journal of Neuromuscular Diseases 2024The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD).
METHODS
This systematic review and meta-analysis included searches of MEDLINE ALL, Embase, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of loss of ambulation in DMD. Search terms included "Duchenne muscular dystrophy" as a Medical Subject Heading or free text term, in combination with variations of the term "predictor". Risk of bias was assessed using the Newcastle-Ottawa Scale. We performed meta-analysis pooling of hazard ratios of the effects of glucocorticoids (vs. no glucocorticoid therapy) by fitting a common-effect inverse-variance model.
RESULTS
The bibliographic searches resulted in the inclusion of 45 studies of children and adults with DMD from 17 countries across Europe, Asia, and North America. Glucocorticoid therapy was associated with delayed loss of ambulation (overall meta-analysis HR deflazacort/prednisone/prednisolone: 0.44 [95% CI: 0.40-0.48]) (n = 25 studies). Earlier onset of first signs or symptoms, earlier loss of developmental milestones, lower baseline 6MWT (i.e.,<350 vs. ≥350 metres and <330 vs. ≥330 metres), and lower baseline NSAA were associated with earlier loss of ambulation (n = 5 studies). Deletion of exons 3-7, proximal mutations (upstream intron 44), single exon 45 deletions, and mutations amenable of skipping exon 8, exon 44, and exon 53, were associated with prolonged ambulation; distal mutations (intron 44 and downstream), deletion of exons 49-50, and mutations amenable of skipping exon 45, and exon 51 were associated with earlier loss of ambulation (n = 13 studies). Specific single-nucleotide polymorphisms in CD40 gene rs1883832, LTBP4 gene rs10880, SPP1 gene rs2835709 and rs11730582, and TCTEX1D1 gene rs1060575 (n = 7 studies), as well as race/ethnicity and level of family/patient deprivation (n = 3 studies), were associated with loss of ambulation. Treatment with ataluren (n = 2 studies) and eteplirsen (n = 3 studies) were associated with prolonged ambulation. Magnetic resonance biomarkers (MRI and MRS) were identified as significant predictors of loss of ambulation (n = 6 studies). In total, 33% of studies exhibited some risk of bias.
CONCLUSION
Our synthesis of predictors of loss of ambulation in DMD contributes to the understanding the natural history of disease and informs the design of new trials of novel therapies targeting this heavily burdened patient population.
Topics: Muscular Dystrophy, Duchenne; Humans; Glucocorticoids; Walking; Pregnenediones; Latent TGF-beta Binding Proteins
PubMed: 38669554
DOI: 10.3233/JND-230220 -
Archives of Gynecology and Obstetrics Jun 2024Gynecologic perivascular epithelioid cell (PEC) tumors, or 'PEComas,' represent a rare and intriguing subset of tumors within the female reproductive tract. This... (Review)
Review
Gynecologic perivascular epithelioid cell (PEC) tumors, or 'PEComas,' represent a rare and intriguing subset of tumors within the female reproductive tract. This systematic literature review aims to provide an updated understanding of gynecologic PEComas based on available literature and data. Although PEComa is rare, there are varied tumor-site presentations across gynecologic organs, with uterine PEComas being the most prevalent. There is scarce high-quality literature regarding gynecologic PEComa, and studies on malignant PEComa underscore the challenges in diagnosis. Among the diverse mutations, mTOR alterations are the most prominent. Survival analysis reveals a high rate of local recurrence and metastatic disease, which commonly affects the lungs. Treatment strategies are limited, however mTOR inhibitors have pivotal role when indicated and chemotherapy may also be used. with some cases demonstrating promising responses. The paucity of data underscores the need for multicentric studies, an international registry for PEComas, and standardized reporting in case series to enhance clinical and pathological data.
Topics: Humans; Perivascular Epithelioid Cell Neoplasms; Female; Genital Neoplasms, Female; MTOR Inhibitors; Uterine Neoplasms; TOR Serine-Threonine Kinases; Neoplasm Recurrence, Local
PubMed: 38664269
DOI: 10.1007/s00404-024-07510-5 -
Annals of Hematology Jun 2024Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between... (Meta-Analysis)
Meta-Analysis
Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.
Topics: Polycythemia Vera; Janus Kinase 2; Humans; Alleles; Gene Frequency; Amino Acid Substitution; Mutation, Missense
PubMed: 38652240
DOI: 10.1007/s00277-024-05754-4 -
PloS One 2024Echogenic Intracardiac Foci (EIF) are non-structural markers identified during the routine 18-20-week foetal anomaly ultrasound scan yet their clinical significance on...
BACKGROUND
Echogenic Intracardiac Foci (EIF) are non-structural markers identified during the routine 18-20-week foetal anomaly ultrasound scan yet their clinical significance on future outcomes for the infant is unclear.
OBJECTIVE
To examine the association between EIF and risk of preterm birth, chromosomal abnormalities, and cardiac abnormalities.
DESIGN
A review across four databases to identify English language journal articles of EIF using a cohort study design. All studies were reviewed for quality using the Critical Appraisal Skills Programme (CASP) checklist and data extracted for comparison and analysis.
RESULTS
19 papers from 9 different countries were included. Combining these studies showed 4.6% (95% CI = 4.55-4.65%) of all pregnancies had EIF which was on the left in 86% of cases, on the right in 3% of cases and bilaterally in 10%. There was no evidence that EIF was associated with higher rates of preterm birth. However, it is possible that infants with EIF were more likely to be terminated rather than be born preterm as there was a 2.1% (range 0.3-4.2%) rate of termination or death of the foetus after week 20 among those with EIF. There was no evidence that EIF alone is highly predictive of chromosomal abnormalities. There was evidence that EIF is associated with higher rates of minor cardiac abnormalities (e.g. ventricular septal defect, tricuspid regurgitation or mitral regurgitation)) with 5.1% (224 of 4385) of those with EIF showing cardiac abnormalities (3.08% in retrospective studies and 17.85% in prospective studies). However, the risk of cardiac defects was only higher with right-sided EIF and where the EIF persisted into the third trimester. However, this is a rare event and would be seen in an estimated 4 per 10,000 pregnancies.
CONCLUSION
EIF alone was not associated with adverse outcomes for the infant. Only persistent EIF on the right side showed evidence of carrying a higher risk of cardiac abnormality and would warrant further follow-up.
Topics: Female; Humans; Pregnancy; Chromosome Aberrations; Heart Defects, Congenital; Pregnancy Outcome; Pregnancy Trimester, Second; Premature Birth; Ultrasonography, Prenatal
PubMed: 38648215
DOI: 10.1371/journal.pone.0298365 -
Frontiers in Immunology 2024At present, several important trials have been published show that perioperative immunotherapy combined with chemotherapy can improve the prognosis of patients with... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of neoadjuvant immunotherapy plus chemotherapy followed by adjuvant immunotherapy in resectable non-small cell lung cancer: a meta-analysis of phase 3 clinical trials.
OBJECTIVE
At present, several important trials have been published show that perioperative immunotherapy combined with chemotherapy can improve the prognosis of patients with resectable non-small cell lung cancer, which further optimizes treatment options. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of perioperative immunotherapy combined with chemotherapy in resectable non-small cell lung cancer.
METHODS
The following databases were searched for relevant studies: PubMed, EMBASE, Cochrane library (updated 12 October 2023). All randomized trials comparing perioperative immunotherapy combined with chemotherapy versus chemotherapy alone in resectable non-small cell lung cancer were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), event-free survival (EFS), pathological complete response (pCR), major pathological response (MPR), R0 resection rate, rate of underwent surgery and adverse events (AEs).
RESULTS
A total of 2912 patients (1453 receiving perioperative immunotherapy plus chemotherapy and 1459 receiving chemotherapy alone) were included in this systematic review and meta-analysis. The result showed that compared with chemotherapy alone, combined therapy significantly improved OS (HR = 0.68;95% CI: 0.56-0.83), EFS (HR = 0.58;95% CI: 0.51-0.65), pCR (OR = 7.53;95% CI: 4.63-12.26), MPR (OR = 5.03;95% CI: 3.40-7.44), R0 resection (OR = 1.58;95% CI: 1.152.18) and rate of underwent surgery (OR = 1.25;95% CI: 1.04-1.49). However, combination therapy was associated with higher risk of severe adverse event (OR = 1.46;95% CI: 1.19-1.78; P=0.0002), grade 3 and higher treatment-related adverse event (TRAE) (OR = 1.25;95% CI: 1.06-1.49; P=0.010), TRAE that led to interruption (OR = 1.90;95% CI: 1.34-2.68; P=0.0003) and immune-related adverse event (OR = 2.78;95% CI: 2.18-3.55; P<0.00001). Significant benefits were observed across most subgroups of EFS and pCR. However, no statistical differences were observed for EFS of never smoked (HR = 0.73;95% CI: 0.51-1.05) and EGFR-mutation positive (HR = 0.35;95% CI: 0.04-3.03).
CONCLUSION
This systematic review and meta-analysis found superior efficacy associated with perioperative immunotherapy plus chemotherapy compared with chemotherapy alone in both tumor regression and prolonged survival in resectable NSCLC, but increased the risk of TRAE, so monitoring for adverse events is warranted.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier (CRD42023476786).
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Immunotherapy; Lung Neoplasms; Neoadjuvant Therapy; Treatment Outcome
PubMed: 38646542
DOI: 10.3389/fimmu.2024.1359302 -
BMC Ophthalmology Apr 2024The goal of the study was to search for novel bi-allelic CRB1 mutations, and then to analyze the CRB1 literature at the genotypic and phenotypic levels. (Meta-Analysis)
Meta-Analysis
PURPOSE
The goal of the study was to search for novel bi-allelic CRB1 mutations, and then to analyze the CRB1 literature at the genotypic and phenotypic levels.
APPROACH
We screened various variables such as the CRB1 mutation types, domains, exons, and genotypes and their relation with specific ocular phenotypes. An emphasis was given to the bi-allelic missense and nonsense mutations because of their high prevalence compared to other mutation types. Finally, we quantified the effect of various non-modifiable factors over the best-corrected visual acuity oculus uterque (BCVA OU) using multivariate linear regression models and identified genetic interactions.
RESULTS
A novel bi-allelic missense in the exon 9 of CRB1; c.2936G > A; p.(Gly979Asp) was found to be associated with rod-cone dystrophy (RCD). CRB1 mutation type, exons, domains, and genotype distribution varied significantly according to fundus characteristics, such as peripheral pigmentation and condition, optic disc, vessels, macular condition, and pigmentation (P < 0.05). Of the 154 articles retrieved from PubMed, 96 studies with 439 bi-allelic CRB1 patients were included. Missense mutations were significantly associated with an absence of macular pigments, pale optic disc, and periphery pigmentation, resulting in a higher risk of RCD (P < 0.05). In contrast, homozygous nonsense mutations were associated with macular pigments, periphery pigments, and a high risk of LCA (P < 0.05) and increased BCVA OU levels. We found that age, mutation types, and inherited retinal diseases were critical determinants of BCVA OU as they significantly increased it by 33% 26%, and 38%, respectively (P < 0.05). Loss of function alleles additively increased the risk of LCA, with nonsense having a more profound effect than indels. Finally, our analysis showed that p.(Cys948Tyr) and p.(Lys801Ter) and p.(Lys801Ter); p.(Cys896Ter) might interact to modify BCVA OU levels.
CONCLUSION
This meta-analysis updated the literature and identified genotype-phenotype associations in bi-allelic CRB1 patients.
Topics: Humans; Alleles; Codon, Nonsense; Nerve Tissue Proteins; Genetic Association Studies; Retina; Phenotype; Mutation; Eye Proteins; Pedigree; DNA Mutational Analysis; Membrane Proteins
PubMed: 38622537
DOI: 10.1186/s12886-024-03419-4