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Frontiers in Oncology 2024Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations...
BACKGROUND
Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations with other histological and molecular markers that impact prognosis and treatment remain to be clarified. We conducted a systematic review and meta-analysis concerning the prevalence of prognostic and predictive tumor markers for early- vs. late-onset CRC, including oncogene mutations, microsatellite instability (MSI), and emerging markers including immune cells and the consensus molecular subtypes.
METHODS
We systematically searched PubMed for original research articles published between April 2013-January 2024. Included studies compared the prevalence of tumor markers in early- vs. late-onset CRC. A meta-analysis was completed and summary odds ratios (ORs) with 95% confidence intervals (CIs) were obtained from a random effects model via inverse variance weighting. A sensitivity analysis was completed to restrict the meta-analysis to studies that excluded individuals with Lynch syndrome, a hereditary condition that influences the distribution of tumor markers for early-onset CRC.
RESULTS
In total, 149 articles were identified. Tumors from early-onset CRC are less likely to include mutations in (OR, 95% CI: 0.91, 0.85-0.98), (0.63, 0.51-0.78), (0.70, 0.58-0.84), and (0.88, 0.78-1.00) but more likely to include mutations in (1.68, 1.04-2.73) and (1.34, 1.24-1.45). After limiting to studies that excluded Lynch syndrome, the associations between early-onset CRC and (0.77, 0.64-0.92) and mutation (0.81, 0.67-0.97) were attenuated, while an inverse association with mutation was also observed (0.88, 0.78-0.99). Early-onset tumors are less likely to develop along the CpG Island Methylator Phenotype pathway (0.24, 0.10-0.57), but more likely to possess adverse histological features including high tumor grade (1.20, 1.15-1.25), and mucinous (1.22, 1.16-1.27) or signet ring histology (2.32, 2.08-2.57). A positive association with MSI status (1.31, 1.11-1.56) was also identified. Associations with immune markers and the consensus molecular subtypes are inconsistent.
DISCUSSION
A lower prevalence of mutations in and is consistent with extended survival and superior response to targeted therapies for metastatic disease. Conversely, early-onset CRC is associated with aggressive histological subtypes and and mutations, which may serve as therapeutic targets.
PubMed: 38737895
DOI: 10.3389/fonc.2024.1349572 -
Mycopathologia May 2024The global spread of Trichophyton indotineae presents a pressing challenge in dermatophytosis management. This systematic review explores the current landscape of T.... (Review)
Review
INTRODUCTION
The global spread of Trichophyton indotineae presents a pressing challenge in dermatophytosis management. This systematic review explores the current landscape of T. indotineae infections, emphasizing resistance patterns, susceptibility testing, mutational analysis, and management strategies.
METHODS
A literature search was conducted in November 2023 using Embase, PubMed, Scopus, and Web of Science databases. Inclusion criteria covered clinical trials, observational studies, case series, or case reports with T. indotineae diagnosis through molecular methods. Reports on resistance mechanisms, antifungal susceptibility testing, and management were used for data extraction.
RESULTS AND DISCUSSION
A total of 1148 articles were identified through the systematic search process, with 45 meeting the inclusion criteria. The global spread of T. indotineae is evident, with cases reported in numerous new countries in 2023. Tentative epidemiological cut-off values (ECOFFs) suggested by several groups provide insights into the likelihood of clinical resistance. The presence of specific mutations, particularly Phe397Leu, correlate with higher minimum inhibitory concentrations (MICs), indicating potential clinical resistance. Azole resistance has also been reported and investigated in T. indotineae, and is a growing concern. Nevertheless, itraconazole continues to be an alternative therapy. Recommendations for management include oral or combination therapies and individualized approaches based on mutational analysis and susceptibility testing.
CONCLUSION
Trichophyton indotineae poses a complex clinical scenario, necessitating enhanced surveillance, improved diagnostics, and cautious antifungal use. The absence of established clinical breakpoints for dermatophytes underscores the need for further research in this challenging field.
Topics: Antifungal Agents; Humans; Drug Resistance, Fungal; Mutation; Microbial Sensitivity Tests; Tinea; Trichophyton; Global Health
PubMed: 38734753
DOI: 10.1007/s11046-024-00856-z -
Urology Journal May 2024The exact molecular and cellular processes that cause benign urological diseases in the stromal and epithelial components of the urinary tract are yet unknown. Reviewing...
PURPOSE
The exact molecular and cellular processes that cause benign urological diseases in the stromal and epithelial components of the urinary tract are yet unknown. Reviewing and analyzing the data linking microRNAs (miRNAs) expression in the pathophysiology of benign urological conditions, including overactive bladder (OAB), bladder outlet obstruction (BOO), bladder pain syndrome/interstitial cystitis (BPS/IC), and Lower urinary tract dysfunction (LUTD) is the objective of the current systematic review.
MATERIALS AND METHODS
Evidence including all case-control, cohort, and cross-sectional studies that measure participants' MicroRNA as a biomarker for benign urological diseases has been gathered On January 2024, through searching MEDLINE via PubMed, Scopus, Web of Science, Embase, and ProQuest databases. Studies considered eligible that present information on the reference Gene, profile type, and serum levels of microRNA from patients diagnosed with benign urological disease including benign prostate hyperplasia (BPH) or benign prostate enlargement (BPE), overactive bladder (OAB), and bladder outlet obstruction (BOO). These studies appraised by the quality assessment checklist of Joanna Briggs Institute (JBI).
RESULTS
A total of 4,587 records related to miRNAs in urological diseases were retrieved. Of these, we identified 28 records for our systematic study. The most frequently associated miRNA was 92a-3p identified which was found upregulated in OAB diagnosis. In BOO, miR-146a-5p was identified to be upregulated. miR-146a-5p was upregulated in BO, and for other benign conditions, different miRNAs were reported. 491-5p miRNAs were found deregulated in OAB-related studies. We expected other miRNAs to have the same trend in the OAB studies. InSUI miR-93 was the most frequent downregulated miRNA. The other reported miRNAs had similar frequencies.
CONCLUSION
When it comes to the early detection and treatment of benign urological conditions, 92a-3p, miR-21, miR-199a-5p, and miR-146a-5p, and 491-5p have the potential to be employed as both a biomarker and a therapeutic target. The creation of pre-RNA or anti-RNA molecules within carrier vehicles that may be safely administered to patients should be made possible by technological advancements.
PubMed: 38733231
DOI: 10.22037/uj.v21i.7985 -
Journal of Clinical Medicine May 2024: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing,... (Review)
Review
: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing, these tumors often resist conventional chemotherapies (CTs) and radiotherapies (RTs), making surgical resection a crucial intervention. However, achieving radical resection for chordomas is seldom possible, presenting therapeutic challenges. The accurate diagnosis of these tumors is vital for their distinct prognoses, yet differentiation is hindered by overlapping radiological and histopathological features. Fortunately, recent molecular and genetic studies, including extracranial location analysis, offer valuable insights for precise diagnosis. This literature review delves into the genetic aberrations and molecular biology of chordomas, aiming to provide an overview of more successful therapeutic strategies. : A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 28 January 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chordomas", "molecular biology", "gene aberrations", and "target therapies". The studies included in this review consist of preclinical cell studies, case reports, case series, randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on genetic and biological aberrations in chordomas. : Of the initial 297 articles identified, 40 articles were included in the article. Two tables highlighted clinical studies and ongoing clinical trials, encompassing 18 and 22 studies, respectively. The clinical studies involved 185 patients diagnosed with chordomas. The tumor sites were predominantly sacral ( = 8, 44.4%), followed by clivus ( = 7, 38.9%) and lumbar spine ( = 3, 16.7%). Primary treatments preceding targeted therapies included surgery ( = 10, 55.6%), RT ( = 9, 50.0%), and systemic treatments ( = 7, 38.9%). Various agents targeting specific molecular pathways were analyzed in the studies, such as imatinib (a tyrosine kinase inhibitor), erlotinib, and bevacizumab, which target EGFR/VEGFR. Common adverse events included fatigue (47.1%), skin reactions (32.4%), hypertension (23.5%), diarrhea (17.6%), and thyroid abnormalities (5.9%). Clinical outcomes were systematically assessed based on progression-free survival (PFS), overall survival (OS), and tumor response evaluated using RECIST or CHOI criteria. Notably, stable disease (SD) occurred in 58.1% of cases, and partial responses (PRs) were observed in 28.2% of patients, while 13.7% experienced disease progression (PD) despite targeted therapy. Among the 22 clinical trials included in the analysis, Phase II trials were the most prevalent (40.9%), followed by I-II trials (31.8%) and Phase I trials (27.3%). PD-1 inhibitors were the most frequently utilized, appearing in 50% of the trials, followed by PD-L1 inhibitors (36.4%), CTLA-4 inhibitors (22.7%), and mTOR inhibitors (13.6%). : This systematic review provides an extensive overview of the state of targeted therapy for chordomas, highlighting their potential to stabilize the illness and enhance clinical outcomes.
PubMed: 38731241
DOI: 10.3390/jcm13092711 -
Molecular Biology Reports May 2024Treatment-resistant depression (TRD) is a condition in a subset of depressed patients characterized by resistance to antidepressant medications. The global prevalence of... (Review)
Review
BACKGROUND
Treatment-resistant depression (TRD) is a condition in a subset of depressed patients characterized by resistance to antidepressant medications. The global prevalence of TRD has been steadily increasing, yet significant advancements in its diagnosis and treatment remain elusive despite extensive research efforts. The precise underlying pathogenic mechanisms are still not fully understood. Epigenetic mechanisms play a vital role in a wide range of diseases. In recent years, investigators have increasingly focused on the regulatory roles of miRNAs in the onset and progression of TRD. miRNAs are a class of noncoding RNA molecules that regulate the translation and degradation of their target mRNAs via interaction, making the exploration of their functions in TRD essential for elucidating their pathogenic mechanisms.
METHODS AND RESULTS
A systematic search was conducted in four databases, namely PubMed, Web of Science, Cochrane Library, and Embase, focusing on studies related to treatment-resistant depression and miRNAs. The search was performed using terms individually or in combination, such as "treatment-resistant depression," "medication-resistant depression," and "miRNAs." The selected articles were reviewed and collated, covering the time period from the inception of each database to the end of February 2024. We found that miRNAs play a crucial role in the pathophysiology of TRD through three main aspects: 1) involvement in miRNA-mediated inflammatory responses (including miR-155, miR-345-5p, miR-146a, and miR-146a-5p); 2) influence on 5-HT transport processes (including miR-674,miR-708, and miR-133a); and 3) regulation of synaptic plasticity (including has-miR-335-5p,has-miR- 1292-3p, let-7b, and let-7c). Investigating the differential expression and interactions of these miRNAs could contribute to a deeper understanding of the molecular mechanisms underlying TRD.
CONCLUSIONS
miRNAs might play a pivotal role in the pathogenesis of TRD. Gaining a deeper understanding of the roles and interrelations of miRNAs in TRD will contribute to elucidating disease pathogenesis and potentially provide avenues for the development of novel diagnostic and therapeutic strategies.
Topics: Humans; MicroRNAs; Depressive Disorder, Treatment-Resistant; Antidepressive Agents; Gene Expression Regulation; Epigenesis, Genetic
PubMed: 38727891
DOI: 10.1007/s11033-024-09554-x -
Viral Immunology May 2024In May 2022, mpox began to spread worldwide, posing a serious threat to human public health. Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) is a live attenuated... (Meta-Analysis)
Meta-Analysis
In May 2022, mpox began to spread worldwide, posing a serious threat to human public health. Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) is a live attenuated orthopoxvirus vaccine that has been authorized by the U.S. Food and Drug Administration as the vaccine of choice for the prevention of mpox. In this study, we conducted a meta-analysis of all currently published literature on the efficacy and safety of the MVA-BN vaccine in the real world, showing that the MVA-BN vaccine is effective and safe, with efficacy of up to 75% with a single dose and up to 80% with a two-dose vaccine. Meanwhile, we found that subcutaneous injection has lower local and systemic adverse events than intradermal injection, regardless of single- or two-dose vaccination, and subcutaneous injection is better tolerated in children, the elderly, or people with underlying medical conditions. These results have important reference value for clinical practice.
Topics: Humans; Vaccine Efficacy; Vaccines, Attenuated; Poxviridae Infections; Vaccinia virus; Vaccination; Injections, Subcutaneous; Injections, Intradermal; Viral Vaccines; Orthopoxvirus; Child
PubMed: 38717823
DOI: 10.1089/vim.2023.0147 -
European Archives of... May 2024Lipoid proteinosis (LP) or Urbach-Wiethe disease (OMIM 247100) is a rare syndrome characterised by early vocal folds infiltration and subsequent multi-organ involvement.... (Review)
Review
PURPOSE
Lipoid proteinosis (LP) or Urbach-Wiethe disease (OMIM 247100) is a rare syndrome characterised by early vocal folds infiltration and subsequent multi-organ involvement. LP is often unrecognised and its associated hoarseness is overlooked. The main objective of the study was to investigate hoarseness in LP and implement a diagnosis among otolaryngologists.
METHODS
PubMed/MEDLINE and OMIM databases were systematically searched. Authors concentrated the search on published articles starting from the discovery of the pathogenesis of LP by Hamada et al. in 2002. Only cases in which a diagnosis was reported both clinically and through biopsy and/or genetic molecular testing were included. Characteristics of the LP cases were extracted from each included study. Results were obtained through Generalized Estimating Equations.
RESULTS
The search strategy yielded 217 articles, of which 74 (34.1%) met the selection criteria. A total of 154 cases were included. Hoarseness was described in all LP cases and clearly stated as the onset symptom in 68.8%. The onset was on average at 19 months of age (CI: 3.00-20.00), while the mean age at diagnosis was 15 years (CI: 10.00-30.00). Therefore, the diagnostic delay amounted to 13.42 years (CI: 8.00-23.83). Hoarseness alone was responsible for an LP diagnosis in only 14.3% of cases. In 43.5% of cases, genetic analysis of the ECM1 gene was performed and exon 6 was the most frequently altered portion.
CONCLUSION
Analysing the largest number of published cases, the study underlined that hoarseness is the key symptom for diagnosing LP since early childhood, though frequently overlooked.
PubMed: 38713291
DOI: 10.1007/s00405-024-08713-x -
The International Journal of Lower... May 2024Charcot neuro-osteoarthropathy (CNO) is a complication of diabetes occurring in people with diabetic neuropathy with a prevalence of 0.5% to 1% that may culminate to... (Review)
Review
Charcot neuro-osteoarthropathy (CNO) is a complication of diabetes occurring in people with diabetic neuropathy with a prevalence of 0.5% to 1% that may culminate to foot deformity, amputation, and early mortality. However, it is not known why only certain patients with diabetic neuropathy develop CNO. Hence, early recognition of risk factors, timely diagnosis, and appropriate intervention of CNO is pertinent. Recent understanding of the pathophysiology of CNO has expanded to suggest the involvement of pathways. But pharmaco-therapeutic interventions targeting bone metabolism predominantly inhibiting were not found to be useful. Moreover, there are not enough markers to help identify patients with diabetes who are at a higher risk of developing CNO. Hence, we explored the literature in the present systematic review of mainly case-control studies to identify genetic factors that could help in understanding the pathophysiology and risk factors for the development of CNO. We could identify 7 relevant studies identifying single nucleotide polymorphism of and genes. There is an isolated study identifying alterations of micro RNA associated with pathway. Another study found epigenetic alterations by performing whole methylome sequencing in people with CNO compared to control. These genetic factors can be used as a diagnostic marker and their functional counterparts as targets for future therapeutic interventions. However, we found that literature is sparse on the genetic risk factors for CNO in people with diabetic neuropathy and there is still a lot of scope for future studies towards finding the molecular and genetic markers for CNO.
PubMed: 38711285
DOI: 10.1177/15347346241252549 -
BMC Public Health May 2024A notable research gap exists in the systematic review and meta-analysis concerning the efficacy, immunogenicity, and safety of the respiratory syncytial virus (RSV)... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
A notable research gap exists in the systematic review and meta-analysis concerning the efficacy, immunogenicity, and safety of the respiratory syncytial virus (RSV) prefusion F vaccine.
METHODS
We conducted a comprehensive search across PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov to retrieve articles related to the efficacy, immunogenicity, and safety of RSV prefusion F vaccines, published through September 8, 2023. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
A total of 22 randomized controlled trials involving 78,990 participants were included in this systematic review and meta-analysis. The RSV prefusion F vaccine exhibited a vaccine effectiveness of 68% (95% CI: 59-75%) against RSV-associated acute respiratory illness, 70% (95% CI: 60-77%) against medically attended RSV-associated lower respiratory tract illness, and 87% (95% CI: 71-94%) against medically attended severe RSV-associated lower respiratory tract illness. Common reported local adverse reactions following RSV prefusion F vaccination include pain, redness, and swelling at the injection site, and systemic reactions such as fatigue, headache, myalgia, arthralgia, nausea, and chills.
CONCLUSIONS
Our meta-analysis suggests that vaccines using the RSV prefusion F protein as antigen exhibit appears broadly acceptable efficacy, immunogenicity, and safety in the population. In particular, it provides high protective efficiency against severe RSV-associated lower respiratory tract disease.
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Vaccine Efficacy; Respiratory Syncytial Virus, Human; Immunogenicity, Vaccine; Randomized Controlled Trials as Topic
PubMed: 38711074
DOI: 10.1186/s12889-024-18748-8 -
Prenatal Diagnosis Jun 2024To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification.
METHODS
A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747.
RESULTS
Overall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%-21.6%), 9.3% (95% CI, 6.6%-12.3%) and 35.9% (95% CI, 21.0%-52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%-65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%).
CONCLUSION
The likelihood of a monogenic aetiology in fetuses with multi-system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions.
Topics: Humans; Heart Defects, Congenital; Female; Pregnancy; Exome Sequencing; Prenatal Diagnosis
PubMed: 38708840
DOI: 10.1002/pd.6581