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Cureus Aug 2023Being one of the most prevalent progressive neurodegenerative disorders (falling second only to Alzheimer's disease) with a clinical pattern affecting millions of lives... (Review)
Review
Being one of the most prevalent progressive neurodegenerative disorders (falling second only to Alzheimer's disease) with a clinical pattern affecting millions of lives all over the world, Parkinson's disease (PD) has never failed to attract a formidable interest from the vast majority of neurologists and researchers worldwide. This review article will analyze the pathophysiology, etiology, genetics, and pathological stages of Parkinson's disease with their corresponding clinical sequels. A review article was conducted using research databases including PubMed, PubMed Central, Springer, and Elsevier. The research articles reviewed using databases were written in English, German, Japanese, and Chinese and published within the preceding 50 years. Based on the article's findings, we concluded that Parkinson's disease is a progressive disorder with a variety of motor and non-motor symptoms that are influenced by a cascade of pathological neuronal abnormalities such as Lewy neurites and Lewy bodies that gradually build up with an eventual consequence of neurodegeneration of dopamine-secreting neurons. Multiple genetic mutations, pathophysiological events, and environmental factors act as the foundation to initiate that cascade.
PubMed: 37664277
DOI: 10.7759/cureus.44353 -
Diagnostics (Basel, Switzerland) Sep 2023mutation () is the most frequent point mutation in non-small cell lung cancer (NSCLC) and has been proven to be a predictive biomarker for direct inhibitors in... (Review)
Review
mutation () is the most frequent point mutation in non-small cell lung cancer (NSCLC) and has been proven to be a predictive biomarker for direct inhibitors in advanced solid cancers. We sought to determine the prognostic significance of in patients with NSCLC using the meta-analytic approach. A protocol is registered at the International Prospective Register for systematic reviews (CRD42022345868). PubMed, EMBASE, The Cochrane Library, and Clinicaltrials.gov.in were searched for prospective or retrospective studies reporting survival data for tumors with compared with either other mutations or wild-type (-). The hazard ratios (HRs) for overall survival (OS) or Disease-free survival (DFS) of tumors were pooled according to fixed or random-effects models. Sixteen studies enrolling 10,153 participants were included in the final analysis. tumors had poor OS [] but similar DFS [HR 2.36, 95% CI 0.64-8.16] compared to tumors. Compared to other mutations, tumors had poor DFS [] but similar OS [HR, 1.03; 95% CI, 0.84-1.26]. Compared to other mutations, high PD-L1 expression (>50%) [] was associated with tumors. is a promising prognostic factor for patients with NSCLC, negatively impacting survival. Prevailing significant heterogeneity and selection bias might reduce the validity of these findings. Concomitant high PD-L1 expression in these tumors opens doors for exciting therapeutic potential.
PubMed: 37835787
DOI: 10.3390/diagnostics13193043 -
Frontiers in Endocrinology 2023Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT.
METHODS
Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0.
RESULTS
In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients.
CONCLUSION
This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort.
Topics: Humans; Thyroid Cancer, Papillary; Hashimoto Disease; Proto-Oncogene Proteins B-raf; Thyroid Neoplasms; Lymphatic Metastasis; Prevalence; Carcinoma, Papillary; Mutation
PubMed: 38047109
DOI: 10.3389/fendo.2023.1273498 -
Clinical and Experimental Medicine Oct 2023Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies that mostly affect the elderly and have poor prognoses. Mutations in... (Meta-Analysis)
Meta-Analysis
Efficacy of epigenetic agents for older patients with acute myeloid leukemia and myelodysplastic syndrome in randomized controlled trials: a systematic review and network meta-analysis.
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies that mostly affect the elderly and have poor prognoses. Mutations in epigenetic regulatory genes cause AML/MDS through changes in DNA methylation and histone modifications. Some epigenetic agents are used in patients with AML and MDS. However, most studies have focused on azacitidine (AZA) or decitabine (DEC), and few studies have been conducted on combination therapies or other epigenetic therapies. This network meta-analysis (NMA) aimed to compare the efficacy of epigenetic agents overall in patients with AML and MDS. A systematic review and NMA of all available II-III phase randomized controlled trials (RCTs) comparing epigenetic agents were performed. The Embase and PubMed databases were searched for relevant studies. The Bayesian model was used in the NMA, and the surface under the cumulative ranking curve (SUCRA) was used to rank comparisons. The primary endpoint was overall survival (OS), and the secondary endpoints were complete response (CR) and partial response (PR). OS was extended by AZA + venetoclax (SUCRA 0.94) in patients with AML and MDS. DEC (SUCRA 0.78) relatively improved CR and PR. In this study, AZA-related treatment was relatively effective in improving the OS of patients with AML and MDS, and DEC-related treatment showed a relatively high effect on CR and PR. The protocol for this systematic review was registered with the International Prospective Register of Systematic Reviews (CRD42022303601).
Topics: Aged; Humans; Azacitidine; Epigenesis, Genetic; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Network Meta-Analysis; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Treatment Outcome
PubMed: 36964818
DOI: 10.1007/s10238-023-01041-0 -
Journal of Neurology Nov 2023Acute necrotizing encephalopathy (ANE) is a rare neurological complication related to COVID-19. Here we present a case series of six Chinese cases with ANE associated... (Review)
Review
Acute necrotizing encephalopathy (ANE) is a rare neurological complication related to COVID-19. Here we present a case series of six Chinese cases with ANE associated with COVID-19 and review all reported cases in the literature. A total of six cases with ANE related to COVID-19 were enrolled in this study. Clinical manifestations, neuroimaging data, treatment and outcomes of these patients were analyzed. A literature review was performed in Pubmed and Embase and 25 cases with clinical and neuroimaging data were collected and analyzed. Among our six cases, the age of onset ranged from 15 to 56 years, with a male-to-female ratio of nearly 1:1. All patients presented with reduced consciousness. Elevated interleukin 6 in serum and/or cerebrospinal fluid (CSF) was detected in four patients. Two patients improved clinically after intravenous methylprednisolone and intravenous immunoglobulin (IVIG). Based on the literature review, the majority of cases were from Europe and the United States (60%). Two age peaks at 10-20 years (20%) and 50-60 years (28%) were observed. Two cases were found with a heterozygous Thr585Met mutation. The mortality of ANE caused by COVID-19 was 42%. The use of IVIG in combination with other immunotherapies was related to better outcome (P = 0.041) and both two patients who received Tocilizumab survived. This is the first Chinese case series about ANE associated with COVID-19. Elevated serum and CSF interlukin-6 were found in certain cases. The mortality and morbidity rates remained high although prompt immunotherapy could improve the outcomes.
PubMed: 37695531
DOI: 10.1007/s00415-023-11915-8 -
The Journal of Infectious Diseases Nov 2023HIV poses significant challenges for vaccine development due to its high genetic mutation and recombination rates. Understanding the distribution of HIV subtypes... (Meta-Analysis)
Meta-Analysis
Geographic and Population Distributions of Human Immunodeficiency Virus (HIV)-1 and HIV-2 Circulating Subtypes: A Systematic Literature Review and Meta-analysis (2010-2021).
BACKGROUND
HIV poses significant challenges for vaccine development due to its high genetic mutation and recombination rates. Understanding the distribution of HIV subtypes (clades) across regions and populations is crucial. In this study, a systematic review of the past decade was conducted to characterize HIV-1/HIV-2 subtypes.
METHODS
A comprehensive search was performed in PubMed, EMBASE, and CABI Global Health, yielding 454 studies from 91 countries.
RESULTS
Globally, circulating recombinant forms (CRFs)/unique recombinant forms (URFs) accounted for 29% of HIV-1 strains, followed by subtype C (23%) and subtype A (17%). Among studies reporting subtype breakdowns in key populations, 62% of HIV infections among men who have sex with men (MSM) and 38% among people who inject drugs (PWIDs) were CRF/URFs. Latin America and the Caribbean exhibited a 25% increase in other CRFs (excluding CRF01_AE or CRF02_AG) prevalence between 2010-2015 and 2016-2021.
CONCLUSIONS
This review underscores the global distribution of HIV subtypes, with an increasing prevalence of CRFs and a lower prevalence of subtype C. Data on HIV-2 were limited. Understanding subtype diversity is crucial for vaccine development, which need to elicit immune responses capable of targeting various subtypes. Further research is needed to enhance our knowledge and address the challenges posed by HIV subtype diversity.
Topics: Male; Humans; HIV Infections; Homosexuality, Male; HIV-1; HIV-2; Genetic Variation; Phylogeny; Sexual and Gender Minorities; Prevalence; Genotype
PubMed: 37592824
DOI: 10.1093/infdis/jiad327 -
Circulation Jan 2024Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted.
METHODS
A systematic search of the literature was performed. We used random-effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere or sarcomere-related genes in 2 different contexts: clinically-based studies on patients and families with HCM versus population or community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up.
RESULTS
In total, 455 full-text manuscripts and articles were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening was 57% (95% CI, 52%-63%), and the mean age at HCM diagnosis was 38 years (95% CI, 36%-40%). Penetrance varied from ≈32% for (myosin light chain 3) to ≈55% for (myosin-binding protein C3), ≈60% for (troponin T2) and (troponin I3), and ≈65% for (myosin heavy chain 7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population but at a low prevalence of <1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower at ≈11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ≈8 years of follow-up, starting from a mean of ≈16 years of age. However, short-term gene-specific phenotypic conversion varied between ≈12% for and ≈23% for .
CONCLUSIONS
The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve our understanding of true lifetime penetrance in families and in the community and to identify drivers of the transition from subclinical to overt HCM.
Topics: Humans; Adult; Penetrance; Mutation; Cross-Sectional Studies; Pedigree; Cardiomyopathy, Hypertrophic; Troponin T
PubMed: 37929589
DOI: 10.1161/CIRCULATIONAHA.123.065987 -
Cureus Sep 2023Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute... (Review)
Review
Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. The complement cascade plays an integral role in aHUS. Mutations in the complement cascade, especially in the alternative pathway (AP) lead to an unregulated and continuous activation of the cascade. Eculizumab and ravulizumab are humanized monoclonal antibodies that inhibit the complement cascade. This systematic analysis reviews the evidence for both antibodies to compare them in terms of safety and efficacy. This review will also assess the evidence for biomarker associations with interventions, the role of genetic mutations in the prognosis of disease, and the financial burden of both treatment options. An in-depth search was conducted across PubMed, Science Direct, and Cochrane Library following the PRISMA 2020 guidelines. Both eculizumab and ravulizumab were comparable in safety and efficacy but ravulizumab was preferred by patients and their caregivers as it posed a lower financial burden and had less frequent dosing. Soluble complement 5b-9 (sC5b), especially in urine, has the potential to be used as a biomarker to assess response to treatment. Genetic mutations, especially mutations in complement factor I (CFI), membrane cofactor protein (MCP), and complement factor H (CFH), were associated with a higher risk of recurrence, and therefore care should be taken when attempting to discontinue treatment in this subset of patients. Treatment with a monoclonal antibody should be initiated as soon as a genetic mutation is identified. Blinded, double-arm, clinical trials preferably with larger sample sizes are needed to effectively compare both the monoclonal antibodies.
PubMed: 37905269
DOI: 10.7759/cureus.46185 -
BMC Pediatrics Oct 2023Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic...
BACKGROUND
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS.
METHODS
We searched the WangFang and China National Knowledge Infrastructure databases with the keywords "Shwachman-Diamond syndrome," "SDS," "SBDS gene" and "inherited bone marrow failure" for relevant articles published from January 2002 to October 2022. In addition, studies published from January 2002 to October 2022 were searched from the Web of Science, PubMed, and MEDLINE databases, using "Shwachman-diamond syndrome" as the keyword. Finally, one child with SDS treated in Tongji Hospital was also included.
RESULTS
The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). The detection rate of SDS mutations was 94.6% (125/132). Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported. The male-to-female ratio was approximately 1.3/1. The median age of onset was 0.16 years, but the diagnostic age lagged by a median age of 1.3 years.
CONCLUSIONS
Pancreatic exocrine insufficiency and growth failure were common initial symptoms. SDS onset occurred early in childhood, and individual differences were obvious. Comprehensive collection and analysis of case-related data can help clinicians understand the clinical characteristics of SDS, which may improve early diagnosis and promote effective clinical intervention.
Topics: Female; Humans; Infant; Male; Bone Marrow Diseases; Exocrine Pancreatic Insufficiency; Mutation; Phenotype; Shwachman-Diamond Syndrome; Signal Recognition Particle
PubMed: 37803383
DOI: 10.1186/s12887-023-04324-3 -
Endocrine Dec 2023Data on silent corticotroph tumor (SCT) are still heterogeneous and controversial. In this study, we aimed to compare the demographic, clinicopathological... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Data on silent corticotroph tumor (SCT) are still heterogeneous and controversial. In this study, we aimed to compare the demographic, clinicopathological manifestations, postoperative complications, and patient outcomes of SCTs with other non-functioning pituitary neuroendocrine tumor (NFT) and functioning corticotroph tumor (FCT) or so-called Cushing disease adenoma.
METHODS
We searched PubMed and Web of Science for data of interest. Odds ratio (OR), mean difference (MD), hazard ratio (HR), and their 95% confidence intervals (CI) were pooled using the random-effect model.
RESULTS
Twenty-nine studies with 985 SCTs were included in meta-analyses. In comparison to other NFTs, SCTs were more commonly associated with female gender, younger age, cavernous sinus invasion, apoplexy, and radiotherapy administration. Postoperatively, SCT patients were more likely to experience hypocortisolism, new-onset visual disturbances, and a higher risk for tumor progression than other NFTs. We did not find any significant differences between SCT type I and type II. Compared to FCTs, SCTs were more likely male, older age, and had larger tumor sizes. The prevalence of a USP8 mutation was significantly higher in FCT than in SCT.
CONCLUSION
SCT was demographically, clinicopathologically, and prognostically distinct from other NFTs and FCTs. These tumors should be considered high-risk; appropriate treatment decisions and more stringent follow-up should be tailored to improve patient outcomes.
Topics: Humans; Male; Female; Corticotrophs; Adenoma; Pituitary Neoplasms; Pituitary ACTH Hypersecretion; Prognosis; ACTH-Secreting Pituitary Adenoma
PubMed: 37462809
DOI: 10.1007/s12020-023-03449-w