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Research and Practice in Thrombosis and... Aug 2023Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population...
BACKGROUND
Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population remains unclear; thus, we aimed to assess the proportion of hereditary thrombophilia via a meta-analysis.
METHODS
Publications from PubMed, EMBASE, web of science, and Cochrane before December 30, 2022, were searched. Studies from Japan, Korea, China, Hong Kong, Taiwan, Singapore, Thailand, Vietnam, Myanmar, and Cambodia were included. Congenital thrombophilia was described as diseases including protein C (PC) deficiency, protein S (PS) deficiency, antithrombin (AT) deficiency, factor (F)V Leiden (FVL), and prothrombin G20210A mutations. Studies were selected by 2 reviewers for methodological quality analysis. A random-effects model was used for the meta-analysis, assuming that estimated effects in the different studies are not identical.
RESULTS
Forty-four studies involving 6453 patients from 7 counties/regions were included in the meta-analysis. The prevalence of PC, PS, and AT deficiencies were 7.1%, 8.3%, and 3.8%, respectively. Among 2924 patients from 22 studies, 5 patients were carriers of FVL mutation. Among 2196 patients from 10 studies, 2 patients were carriers of prothrombin G20210A mutation in a Thailand study.
CONCLUSION
The prevalence of PC, PS, and AT deficiencies was relatively high, while a much lower prevalence of FVL and prothrombin G20210A mutations were identified in East-Asian patients with VTE. Our data stress the relative higher prevalence of PC, PS, and AT deficiencies for thrombophilia in the East-Asian VTE population.
PubMed: 37674867
DOI: 10.1016/j.rpth.2023.102157 -
The Journal of Medicine Access 2023Immunoglobulin replacement therapy (IgRT) benefits patients with primary immuno deficiency (PID) originating from the innate or polygenic defects in the immune system.... (Review)
Review
BACKGROUND
Immunoglobulin replacement therapy (IgRT) benefits patients with primary immuno deficiency (PID) originating from the innate or polygenic defects in the immune system. However, evidence supporting their therapeutic role is not as explicit in secondary immuno deficiency (SID) resulting from the treatment of haematological malignancies.
OBJECTIVES
This study aimed to (1) create a dataset of relevant research papers, which explore the use of IgRT in SID for analysis, (2) assess the risk of bias within this dataset and (3) study the characteristics of these papers.
DESIGN
This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. In addition to the risk of bias, the study characteristics explored in this article included study design, study geographical location and year of publication.
DATA SOURCES AND METHODS
To identify studies relevant to the research question, EMBASE and PubMed databases were searched. The Population, Intervention, Comparison and Outcome (PICO) framework was used to assess study quality. Risk of bias and quality of studies were assessed in accordance with the study design. As one model was not appropriate to assess bias in all articles, several tools were used.
RESULTS
A total of 43 studies were identified from the literature search as relevant to the research objective. The most common study design was a retrospective case-control cohort study ( = 16/43), and randomised trials were among the least commonly used approaches ( = 1). Research in this area is occurring around the globe including the United States ( = 7), Italy ( = 7), China, India, Japan and throughout Europe. The annual number of papers in this area has varied from 2012 ( = 1) to 2021 ( = 7). The studies in this article demonstrated a varied risk of bias, with 9 of the 20 cohort studies scoring less than 5 out of 9 stars.
CONCLUSIONS
Randomised controlled trials are less frequently used to assess access and use of immunoglobulins. More commonly, a retrospective case-control cohort study was used which correlates with the higher risk of bias seen in the studies in this article. Most of the research concerning immunoglobulin use and access occurs in higher-income countries.
PubMed: 37846344
DOI: 10.1177/27550834231197315 -
Nutrients Jul 2023Vitamin D has been shown to have multiple pleiotropic effects beyond bone and mineral metabolism, with purported roles in cardiovascular disease, cancer, and host... (Review)
Review
Vitamin D has been shown to have multiple pleiotropic effects beyond bone and mineral metabolism, with purported roles in cardiovascular disease, cancer, and host immunity. Vitamin D deficiency is common in patients with end-stage kidney disease (ESKD); however, current clinical practice has favored the use of the active hormone. Whether vitamin D deficiency should be corrected in patients with ESKD remains unclear, as few randomized trials have been conducted. In this systematic review, we summarize the current evidence examining whether vitamin D supplementation improves outcomes, beyond mineral metabolism, in patients with ESKD. Data from randomized controlled trials of adults with ESKD were obtained by searching Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection from inception to February 2023. Twenty-three trials composed of 2489 participants were identified for inclusion. Data were synthesized by two independent reviewers and summarized in tables organized by outcome. Outcomes included measures of mortality, cardiovascular disease, inflammation, muscle strength/function, nutrition, patient well-being, and outcomes specific to ESKD including erythropoietin usage, pruritus, and dialysis access maturation. The Cochrane risk of Bias Tool (RoB 2, 2019) was used to assess study quality. Overall, our findings indicate a minimal and varied benefit of native vitamin D supplementation. From the largest studies included, we determine that vitamin D has no demonstrated effect on patient-reported measures of well-being or utilization of erythropoietin, nor does it change levels of the inflammation biomarker -reactive protein. Included trials were heterogeneous with regards to outcomes, and the majority studied small participant populations with a relatively short follow-up. We conclude that vitamin D supplementation corrects vitamin D deficiency and is safe and well-tolerated in humans with ESKD. However, it is not clear from clinical trials conducted to date that a causal pathway exists between 25(OH)D and pleiotropic effects that is responsive to vitamin D treatment.
Topics: Adult; Humans; Vitamin D; Cardiovascular Diseases; Renal Dialysis; Randomized Controlled Trials as Topic; Vitamins; Kidney Failure, Chronic; Vitamin D Deficiency; Dietary Supplements; Erythropoietin; Minerals
PubMed: 37447398
DOI: 10.3390/nu15133072 -
Epilepsia Open Feb 2024Adenylosuccinate lyase (ADSL) deficiency is a rare inherited metabolic disorder with a wide phenotypic presentation, classically grouped into three types (neonatal, type...
Electroclinical features and phenotypic differences in adenylosuccinate lyase deficiency: Long-term follow-up of seven patients from four families and appraisal of the literature.
OBJECTIVE
Adenylosuccinate lyase (ADSL) deficiency is a rare inherited metabolic disorder with a wide phenotypic presentation, classically grouped into three types (neonatal, type I, and type II). We aim to better delineate the pathological spectrum, focusing on the electroclinical characteristics and phenotypic differences of patients with ADSL deficiency.
PATIENTS AND METHODS
Seven patients, from four different families, underwent serial electroencephalogram (EEG), clinical assessment, and neuroimaging. We also performed a systematic review of the cases published in the literature, summarizing the available clinical, neurophysiological, and genetic data.
RESULTS
We report seven previously unreported ADSL deficiency patients with long-term follow-up (10-34 years). From the literature review, we collected 81 previously reported cases. Of the included patient population, 58 % (51/88) were classified as having ADSL deficiency type I, 28% (25/88) as having type II, and 14% (12/88) as having neonatal. The most frequently reported pathogenic variants are p.R426H homozygous (19 patients), p.Y114H in compound heterozygosity (13 patients), and p.D430N homozygous (6 patients). In the majority (89.2%), disease onset was within the first year of life. Epilepsy is present in 81.8% of the patients, with polymorphic and often intractable seizures. EEG features seem to display common patterns and developmental trajectories: (i) poor general background organization with theta-delta activity; (ii) hypsarrhythmia with spasms, usually adrenocorticotropic hormone-responsive; (iii) generalized epileptic discharges with frontal or frontal temporal predominance; and (iv) epileptic discharge activation in sleep with an altered sleep structure. Imaging features present consistent findings of cerebral atrophy with frontal predominance, cerebellar atrophy, and white matter abnormalities among the three types.
SIGNIFICANCE
ADSL deficiency presents variable phenotypic expression, whose severity could be partially attributed to residual activity of the mutant protein. Although a precise phenotype-genotype correlation was not yet feasible, we delineated a common pattern of clinical, neuroradiological, and neurophysiological features.
Topics: Infant, Newborn; Humans; Adenylosuccinate Lyase; Follow-Up Studies; Autistic Disorder; Epilepsy; Atrophy; Purine-Pyrimidine Metabolism, Inborn Errors
PubMed: 37842880
DOI: 10.1002/epi4.12837 -
Frontiers in Endocrinology 2024Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency (IAD) is a rare but potentially fatal disease. (Review)
Review
BACKGROUND
Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency (IAD) is a rare but potentially fatal disease.
METHODS
We comprehensively searched the PubMed database and made a systematic review of immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency. If the status of other anterior pituitary hormones was not mentioned, the case was excluded.
RESULTS
We identified 123 cases diagnosed as immune checkpoint inhibitor-induced IAD, consisting of 44 female and 79 male patients. The average age of these patients was 64.3 ± 12.6 years old, and 67.5% were 60 years old or above. The majority (78.9%) of these patients received anti-programmed cell death protein-1 (anti-PD-1) antibodies or anti-programmed cell death ligand 1 (anti-PD-L1) antibodies or both, and 19.5% received combined therapy, sequential therapy, or both. A total of 26 patients received anti-cytotoxic T lymphocyte antigen 4 antibodies (anti-CTLA-4). The median ICI treatment cycle before the diagnosis of adrenal insufficiency was 8 (6, 12), and the median ICI treatment duration before the diagnosis of adrenal insufficiency was 6 (4, 8) months. Eleven cases developed IAD 1 to 11 months after discontinuation of ICIs. Fatigue and appetite loss were the most common symptoms, and surprisingly, there were two asymptomatic cases of IAD. Most patients (88 cases) had normal pituitary magnetic resonance imaging, only 14 cases reported mild atrophy or swelling pituitary gland, and 21 cases reported no imaging results. Most diagnoses were made by basal hormone levels, and pituitary stimulation tests were performed in only a part of the cases. No cases had been reported of discontinuation of ICI use due to IAD nor had there been any deaths due to IAD.
CONCLUSION
IAD was predominant in elderly male patients mainly receiving anti-PD-1 or anti-PD-L1 antibodies. It was sometimes difficult to recognize IAD at first glance since non-specific symptoms were common and asymptomatic cases of IAD were also reported. Although IAD can be deadly, it usually does not affect the continued use of ICIs.
Topics: Humans; Adrenal Insufficiency; Adrenocorticotropic Hormone; Endocrine System Diseases; Genetic Diseases, Inborn; Hypoglycemia; Immune Checkpoint Inhibitors
PubMed: 38318292
DOI: 10.3389/fendo.2024.1326684 -
Orphanet Journal of Rare Diseases Feb 2024Alpha 1 Antitrypsin Deficiency (AATD) is a largely underrecognized genetic condition characterized by low Alpha 1 Antitrypsin (AAT) serum levels, resulting from... (Review)
Review
BACKGROUND
Alpha 1 Antitrypsin Deficiency (AATD) is a largely underrecognized genetic condition characterized by low Alpha 1 Antitrypsin (AAT) serum levels, resulting from variations in SERPINA1. Many individuals affected by AATD are thought to be undiagnosed, leading to poor patient outcomes. The Z (c.1096G > A; p.Glu366Lys) and S (c.863A > T; p.Glu288Val) deficiency variants are the most frequently found variants in AATD, with the Z variant present in most individuals diagnosed with AATD. However, there are many other less frequent variants known to contribute to lung and/or liver disease in AATD. To identify the most common rare variants associated with AATD, we conducted a systematic literature review with the aim of assessing AATD variation patterns across the world.
METHODS
A systematic literature search was performed to identify published studies reporting AATD/SERPINA1 variants. Study eligibility was assessed for the potential to contain relevant information, with quality assessment and data extraction performed on studies meeting all eligibility criteria. AATD variants were grouped by variant type and linked to the geographical region identified from the reporting article.
RESULTS
Of the 4945 articles identified by the search string, 864 contained useful information for this study. Most articles came from the United States, followed by the United Kingdom, Germany, Spain, and Italy. Collectively, the articles identified a total of 7631 rare variants and 216 types of rare variant across 80 counties. The F (c.739C > T; p.Arg247Cys) variant was identified 1,281 times and was the most reported known rare variant worldwide, followed by the I (c.187C > T; p.Arg63Cys) variant. Worldwide, there were 1492 Null/rare variants that were unidentified at the time of source article publication and 75 rare novel variants reported only once.
CONCLUSION
AATD goes far beyond the Z and S variants, suggesting there may be widespread underdiagnosis of patients with the condition. Each geographical region has its own distinctive variety of AATD variants and, therefore, comprehensive testing is needed to fully understand the true number and type of variants that exist. Comprehensive testing is also needed to ensure accurate diagnosis, optimize treatment strategies, and improve outcomes for patients with AATD.
Topics: Humans; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Germany; Italy; Lung; Spain
PubMed: 38388492
DOI: 10.1186/s13023-024-03069-1 -
Journal of Personalized Medicine May 2024The intestinal wound healing process is a complex event of three overlapping phases: exudative, proliferative, and remodeling. Although some mechanisms have been... (Review)
Review
BACKGROUND
The intestinal wound healing process is a complex event of three overlapping phases: exudative, proliferative, and remodeling. Although some mechanisms have been extensively described, the intestinal healing process is still not fully understood. There are some similarities but also some differences compared to other tissues. The aim of this systematic review was to summarize all studies with knockout (KO) experimental models in bowel anastomoses, underline any recent knowledge, and clarify further the cellular and molecular mechanisms of the intestinal healing process. A systematic review protocol was performed.
MATERIALS AND METHODS
Medline, EMBASE, and Scopus were comprehensively searched.
RESULTS
a total of eight studies were included. The silenced genes included interleukin-10, the four-and-one-half LIM domain-containing protein 2 (FHL2), cyclooxygenase-2 (COX-2), annexin A1 (ANXA-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and heparin-binding epidermal growth factor (HB-EGF) gene. Surgically, an end-to-end bowel anastomosis was performed in the majority of the studies. Increased inflammatory cell infiltration in the anastomotic site was found in IL-10-, annexin-A1-, and TAFI-deficient mice compared to controls. COX-1 deficiency showed decreased angiogenesis at the anastomotic site. Administration of prostaglandin E2 in COX-2-deficient mice partially improved anastomotic leak rates, while treatment of ANXA1 KO mice with Ac2-26 nanoparticles reduced colitis activity and increased weight recovery following surgery.
CONCLUSIONS
our findings provide new insights into improving intestinal wound healing by amplifying the aforementioned genes using appropriate gene therapies. Further research is required to clarify further the cellular and micromolecular mechanisms of intestinal healing.
PubMed: 38929776
DOI: 10.3390/jpm14060553 -
Molecular Genetics and Metabolism... Jun 2024Pompe disease is a rare genetic disorder characterized by a deficiency of acid α-glucosidase (GAA), leading to the accumulation of glycogen in various tissues,...
Pompe disease is a rare genetic disorder characterized by a deficiency of acid α-glucosidase (GAA), leading to the accumulation of glycogen in various tissues, especially in skeletal muscles. The disease manifests as a large spectrum of phenotypes from infantile-onset Pompe disease (IOPD) to late-onset Pompe disease (LOPD), depending on the age of symptoms onset. Quantifying GAA activity and glycogen content in skeletal muscle provides important information about the disease severity. However, the distribution of GAA and glycogen levels in skeletal muscles from healthy individuals and those impacted by Pompe disease remains poorly understood, and there is currently no universally accepted standard assay for GAA activity measurement. This systematic literature review aims to provide an overview of the available information on GAA activity and glycogen content levels in skeletal muscle biopsies from patients with Pompe disease. A structured review of PubMed and Google Scholar literature (with the latter used to check that no additional publications were identified) was conducted to identify peer-reviewed publications on glycogen storage disease type II [MeSH term] + GAA, protein human (supplementary concept), Pompe, muscle; and muscle, acid alpha-glucosidase. A limit of English language was applied. Results were grouped by methodologies used to quantify GAA activity and glycogen content in skeletal muscle. The search and selection strategy were devised and carried out in line with Preferred Reporting of Items in Systematic Reviews and Meta-Analysis guidelines and documented using a flowchart. Bibliographies of papers included in the analysis were reviewed and applicable publications not already identified in the search were included. Of the 158 articles retrieved, 24 (comprising >100 muscle biopsies from >100 patients) were included in the analysis, with four different assays. Analysis revealed that patients with IOPD exhibited markedly lower GAA activity in skeletal muscles than those with LOPD, regardless of the measurement method employed. Additionally, patients with IOPD had notably higher glycogen content levels in skeletal muscles than those with LOPD. In general, however, it was difficult to fully characterize GAA activity because of the different methods used. The findings underscore the challenges in the interpretation and comparison of the results across studies because of the substantial methodological variations. There is a need to establish standardized reference ranges of GAA activity and glycogen content in healthy individuals and in Pompe disease patients based on globally standardized methods to improve comparability and reliability in assessing this rare disease.
PubMed: 38698877
DOI: 10.1016/j.ymgmr.2024.101085 -
SAGE Open Medicine 2024Although tuberculosis is highly prevalent in low- and middle-income countries, millions of cases remain undetected using current diagnostic methods. To address this... (Review)
Review
BACKGROUND
Although tuberculosis is highly prevalent in low- and middle-income countries, millions of cases remain undetected using current diagnostic methods. To address this problem, researchers have proposed prediction rules.
OBJECTIVE
We analyzed existing prediction rules for the diagnosis of pulmonary tuberculosis and identified factors with a moderate to high strength of association with the disease.
METHODS
We conducted a comprehensive search of relevant databases (MEDLINE/PubMed, Cochrane Library, Science Direct, Global Health for Reports, and Google Scholar) up to 14 November 2022. Studies that developed diagnostic algorithms for pulmonary tuberculosis in adults from low and middle-income countries were included. Two reviewers performed study screening, data extraction, and quality assessment. The study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. We performed a narrative synthesis.
RESULTS
Of the 26 articles selected, only half included human immune deficiency virus-positive patients. In symptomatic human immune deficiency virus patients, radiographic findings and body mass index were strong predictors of pulmonary tuberculosis, with an odds ratio of >4. However, in human immune deficiency virus-negative individuals, the biomarkers showed a moderate association with the disease. In symptomatic human immune deficiency virus patients, a C-reactive protein level ⩾10 mg/L had a sensitivity and specificity of 93% and 40%, respectively, whereas a trial of antibiotics had a specificity of 86% and a sensitivity of 43%. In smear-negative patients, anti-tuberculosis treatment showed a sensitivity of 52% and a specificity of 63%.
CONCLUSIONS
The performance of predictors and diagnostic algorithms differs among patient subgroups, such as in human immune deficiency virus-positive patients, radiographic findings, and body mass index were strong predictors of pulmonary tuberculosis. However, in human immune deficiency virus-negative individuals, the biomarkers showed a moderate association with the disease. A few models have reached the World Health Organization's recommendation. Therefore, more work should be done to strengthen the predictive models for tuberculosis screening in the future, and they should be developed rigorously, considering the heterogeneity of the population in clinical work.
PubMed: 38764538
DOI: 10.1177/20503121241243238 -
BMC Cancer Jun 2024Poly (ADP- ribose) polymerase inhibitors (PARPi) has been increasingly adopted for metastatic castration-resistance prostate cancer (mCRPC) patients with homologous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Poly (ADP- ribose) polymerase inhibitors (PARPi) has been increasingly adopted for metastatic castration-resistance prostate cancer (mCRPC) patients with homologous recombination repair deficiency (HRD). However, it is unclear which PARPi is optimal in mCRPC patients with HRD in 2nd -line setting.
METHOD
We conducted a systematic review of trials regarding PARPi- based therapies on mCRPC in 2nd -line setting and performed a Bayesian network meta-analysis (NMA). Radiographic progression-free survival (rPFS) was assessed as primary outcome. PSA response and adverse events (AEs) were evaluated as secondary outcomes. Subgroup analyses were performed according to specific genetic mutation.
RESULTS
Four RCTs comprised of 1024 patients (763 harbored homologous recombination repair (HRR) mutations) were identified for quantitative analysis. Regarding rPFS, olaparib monotherapy, rucaparib and cediranib plus olaparib showed significant improvement compared with ARAT. Olaparib plus cediranib had the highest surface under cumulative ranking curve (SUCRA) scores (87.5%) for rPFS, followed by rucaparib, olaparib and olaparib plus abiraterone acetate prednisone. For patients with BRCA 1/2 mutations, olaparib associated with the highest probability (98.1%) of improved rPFS. For patients with BRCA-2 mutations, olaparib and olaparib plus cediranib had similar efficacy. However, neither olaparib nor rucaparib showed significant superior effectiveness to androgen receptor-axis-targeted therapy (ARAT) in patients with ATM mutations. For safety, olaparib showed significantly lower ≥ 3 AE rate compared with cediranib plus olaparib (RR: 0.72, 95% CI: 0.51, 0.97), while olaparib plus cediranib was associated with the highest risk of all-grade AE.
CONCLUSION
PARPi-based therapy showed considerable efficacy for mCRPC patients with HRD in 2nd -line setting. However, patients should be treated accordingly based on their genetic background as well as the efficacy and safety of the selected regimen.
TRIAL REGISTRATION
CRD42023454079.
Topics: Humans; Poly(ADP-ribose) Polymerase Inhibitors; Bayes Theorem; Prostatic Neoplasms, Castration-Resistant; Mutation; Male; Phthalazines; Network Meta-Analysis; Piperazines; BRCA2 Protein; Recombinational DNA Repair; Antineoplastic Combined Chemotherapy Protocols; Randomized Controlled Trials as Topic; Progression-Free Survival; Indoles; BRCA1 Protein; Treatment Outcome; Quinazolines
PubMed: 38851712
DOI: 10.1186/s12885-024-12388-2