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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 -
Journal of Clinical Immunology Jun 2024Magnesium transporter 1 (MAGT1) gene loss-of-function variants lead to X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-glycosylation...
Magnesium transporter 1 (MAGT1) gene loss-of-function variants lead to X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-glycosylation defect (XMEN), a condition with a variety of clinical and immunological effects. In addition, MAGT1 deficiency has been classified as a congenital disorder of glycosylation (CDG) due to its unique role in glycosylation of multiple substrates including NKG2D, necessary for viral protection. Due to the predisposition for EBV, this etiology has been linked with hemophagocytic lymphohistiocytosis (HLH), however only limited literature exists. Here we present a complex case with HLH and EBV-driven classic Hodgkin lymphoma (cHL) as the presenting manifestation of underlying immune defect. However, the patient's underlying immunodeficiency was not identified until his second recurrence of Hodgkin disease, recurrent episodes of Herpes Zoster, and after he had undergone autologous hematopoietic stem cell transplant (HSCT) for refractory Hodgkin lymphoma. This rare presentation of HLH and recurrent lymphomas without some of the classical immune deficiency manifestations of MAGT1 deficiency led us to review the literature for similar presentations and to report the evolving spectrum of disease in published literature. Our systematic review showcased that MAGT1 predisposes to multiple viruses (including EBV) and adds risk of viral-driven neoplasia. The roles of MAGT1 in the immune system and glycosylation were highlighted through the multiple organ dysfunction showcased by the previously validated Immune Deficiency and Dysregulation Activity (IDDA2.1) score and CDG-specific Nijmegen Pediatric CDG Rating Scale (NPCRS) score for the patient cohort in the systematic review.
Topics: Humans; Male; Cation Transport Proteins; Epstein-Barr Virus Infections; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Hodgkin Disease; Lymphohistiocytosis, Hemophagocytic; Recurrence
PubMed: 38896122
DOI: 10.1007/s10875-024-01749-y -
Annals of Hematology Apr 2024Iron resistance iron deficiency anaemia is a rare autosomal recessive disorder characterized by hypochromic microcytic anaemia, low transferrin saturation and... (Review)
Review
Iron resistance iron deficiency anaemia is a rare autosomal recessive disorder characterized by hypochromic microcytic anaemia, low transferrin saturation and inappropriately high hepcidin levels. The aetiology of this condition is rooted in genetic variations within the transmembrane serine protease 6 (TMPRSS6) genes, responsible for encoding matriptase-2, a pivotal negative regulator of hepcidin. We conducted a systematic search across four electronic databases, yielding 538 articles in total out of which 25 were finally included and were preceded further, aiming to prognosticate prevalent single nucleotide polymorphisms (SNPs) and detrimental genetic alterations. This review aims to elucidate the effects of various SNPs and pathogenic mutations on both haematological and biochemical parameters, as well as their potential interethnic correlation. Employing bioinformatics tools, we subjected over 100 SNPs to scrutiny, discerning their potential functional ramifications. We found rs1373272804, rs1430692214 and rs855791 variants to be most frequent and were having a significant impact on haematological and biochemical profile. We found that individuals of European ancestry were more prone to have these variants compared to other ethnic groups. In conclusion, this review not only sheds light on the association of TMPRSS6 polymorphism in iron resistance iron deficiency anaemia (IRIDA), but also highlights the critical need for further investigations involving larger sample size and more diverse ethnic groups around the globe. These future studies will be vital for gaining a stronger and more reliable understanding of how these genetic differences are linked to the development of IRIDA.
Topics: Humans; Anemia, Iron-Deficiency; Hepcidins; Mutation; Polymorphism, Single Nucleotide; Iron; Membrane Proteins; Serine Endopeptidases
PubMed: 38072851
DOI: 10.1007/s00277-023-05576-w -
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 -
Clinical & Translational Oncology :... Jul 2024Molecular classification of endometrial cancer (EC) has become a promising information to tailor preoperatively the surgical treatment. We aimed to evaluate the rate of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Molecular classification of endometrial cancer (EC) has become a promising information to tailor preoperatively the surgical treatment. We aimed to evaluate the rate of lymph node metastases (LNM) in patients with EC according to molecular profile.
METHODS
A systematic review and meta-analysis were performed according to PRISMA guidelines by searching in two major electronic databases (PubMed and Scopus), including original articles reporting lymph node metastases according to the molecular classification of EC as categorized in the ESGO-ESMO-ESP guidelines.
RESULTS
Fifteen studies enrolling 3056 patients were included. Pooled prevalence LNM when considering only patients undergoing lymph node assessment was 4% for POLE-mutated (95%CI: 0-12%), 22% for no specific molecular profile (95% CI: 9-39%), 23% for Mismatch repair-deficiency (95%CI: 10-40%) and 31% for p53-abnormal (95%CI: 24-39%).
CONCLUSIONS
The presence of LNM seems to be influenced by molecular classification. P53-abnormal group presents the highest rate of nodal involvement, and POLE-mutated the lowest.
Topics: Humans; Endometrial Neoplasms; Female; Lymphatic Metastasis; Tumor Suppressor Protein p53; Mutation; Poly-ADP-Ribose Binding Proteins; DNA Polymerase II; Lymph Nodes; Biomarkers, Tumor
PubMed: 38578538
DOI: 10.1007/s12094-024-03401-y