Nonsteroidal anti-inf lammatory drugs (NSAIDs) are widely prescribed for the treatment of inflammatory diseases, but their use is frequently related to hypersensitivity reactions. This review outlines our current knowledge of NSAID hypersensitivity (NHS) with regard to its pathogenic, molecular, and genetic mechanisms, as well as diagnosis and treatment. The presentation of NHS varies from a local (skin and/or airways) reaction to systemic reactions, including anaphylaxis. At the molecular level, NHS reactions can be classified as cross-reactive (mediated by cyclooxygenase inhibition) or selective (specific activation of immunoglobulin E antibodies or T cells). Genetic polymorphisms and epigenetic factors have been shown to be closely associated with NHS, and may be useful as predictive markers. To diagnose NHS, inhalation or oral challenge tests are applied, with the exclusion of any cross-reactive NSAIDs. For patients diagnosed with NHS, absolute avoidance of NSAIDs/aspirin is essential, and pharmacological treatment, including biologics, is often used to control their respiratory and cutaneous symptoms. Finally, desensitization is recommended only for selected patients with NHS. However, further research is required to develop new diagnostic methods and more effective treatments against NHS.
Anaphylaxis ; Anti-Inflammatory Agents, Non-Steroidal ; Antibodies ; Biological Products ; Diagnosis ; Drug Hypersensitivity* ; Epigenomics ; Genetic Predisposition to Disease ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Inhalation ; Polymorphism, Genetic ; Prostaglandin-Endoperoxide Synthases

Protein tyrosine phosphatase-22 (PTPN22) gene encodes lymphoid-specific tyrosine phosphatase (Lyp), an inhibitor of T cell activation. A polymorphism of the PTPN22 gene has been found to be associated with chronic urticaria (CU). We investigated the associations between PTPN22 gene polymorphisms and CU characteristics, including serum specific IgE antibodies response to toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA). CU patients (n=409) and normal healthy controls (n=388) were enrolled in the present study. Serum specific IgE to TSST-1 and SEA were measured by ImmunoCAP(R). Five PTPN22 single nucleotide polymorphisms, -1123G>C, 1858C>T, 13145A>G, 14943C>T, and 20628A>G, were genotyped. There were no significant differences in genotype or haplotype frequencies of these polymorphisms between the 2 groups. CU patients carrying the GG genotype at 20628A>G (P=0.035) or haplotype 3 [GGG] (P=0.047) had a significantly higher prevalence of serum specific IgE to TSST-1 compared to non-carriers. Similarly, CT/TT genotype at 14943C>T had a significantly higher prevalence of serum specific IgE to SEA (P=0.045). The findings suggest that the PTPN22 gene polymorphisms at 20628A>G and 14943C>T may enhance serum specific IgE responses to TSST-1 and SEA, which may contribute to CU pathogenesis.
Antibodies ; Enterotoxins ; Genotype ; Haplotypes ; Humans ; Immunoglobulin E* ; Polymorphism, Single Nucleotide ; Prevalence ; Shock, Septic ; Superantigens* ; Tyrosine ; Urticaria*

Introduction: The need for gama \u2013 globulin, especially gama - globulin - anti \u2013 HBs, is huge in Vietnam. A number of patients cannot to afford use them due to the high price as they are imported. Meanwhile, Vietnam has high quality input sources for producing gama \u2013 globulin. \r\n', u'Objectives: To study the production process of gama - Globulin from Human Plasma and Standard gama - Globulin with Rich of Anti \u2013 HBs. \r\n', u'Subjects and method: 168 samples of human plasma from voluntary blood donors, which had been screened with for transfusion transmittable infections (TTLs), were chosen as plasma with rich of anti - HBs. The plasma with anti - HBsAg was precipitated with ethanol 25%, pH 6,9 to gain gama - globulin with rich anti - HBs, which was dried by Dutch Ly - 3 - TTE machine. Activation of anti - HBs gama - globulin was identified by a standard method of the degree of antibody specific for anti - HBsAg kit of BIORAD, \r\n', u'Results: The purity of the gama - globulin achieved was 93%, which was almost equal with the results of some foreign researchers (7.8), the activation of anti - HBs was 1:128 dilution degree. The productivity of gama - globulin gaining from 1 litter plasma was 6.0 gram. This new issue was first demonstrated in Vietnam. \r\n', u'Conclusion: We can domestically produce anti-Bs gama - globulin with high degree of activeness (1:128) from human plasma by the precipitating method with ethanol, pH and low temperature. \r\n', u'
Human plasma ; gama - globulin - anti - HBs ; Precipitation of ethanol ; pH and low temperature

Objective: The purpose of this study was to identify factors associated with twin pregnancy following day 3 double embryo transfer (DET). Methods: This retrospective cohort study incorporated data from 16,972 day 3 DET cycles. The participants were women aged between 18 and 45 years who underwent in vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) at My Duc Assisted Reproduction Technique Unit (IVFMD), My Duc Hospital, located in Ho Chi Minh City, Vietnam. Results: Of the 16,972 day 3 DET cycles investigated, 8,812 (51.9%) resulted in pregnancy. Of these, 6,108 cycles led to clinical pregnancy, with 1,543 (25.3% of clinical pregnancies) being twin pregnancies. Factors associated with twin pregnancy included age under 35 years (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.32 to 1.71; p<0.001) and cycles involving the transfer of at least one grade I embryo. Relative to the transfer of two grade III embryos, the risk of twin pregnancy was significantly elevated following the transfer of two grade I embryos (OR, 1.40; 95% CI, 1.16 to 1.69; p<0.001) or a combination of one grade I and one grade II embryo (OR, 1.27; 95% CI, 1.05 to 1.55; p=0.001). Conclusion By analyzing a large number of IVF/ICSI cycles, we identified several predictors of twin pregnancy. These findings can assist medical professionals in tailoring treatment strategies for couples with infertility.

BACKGROUND/AIMS: Role of autophagy in neutrophil function and the association of autophagy and autophagy related (ATG) gene polymorphisms with asthma susceptibility were suggested. In this study, we investigated the genetic association of ATG5 and ATG7 polymorphisms with asthma risk, severity and neutrophilic airway inflammation. METHODS: We recruited 408 asthma patients and 201 healthy controls. Sputum neutrophil counts were determined by H&E staining. Serum interleukin 8 (IL-8) levels were measured by enzyme-linked immunosorbent assay (ELISA). Genetic polymorphisms of ATG5 (-769T>C, -335G>A, and 8830C>T) and ATG7 (-100A>G and 25108G>C) were genotyped. The functional activities of ATG5 -769T>C and -335G>A variants were investigated by luciferase reporter assays. RESULTS: No associations of ATG5 and ATG7 polymorphisms with asthma susceptibility and severity were found. ATG5 -769T>C and -335G>A were in complete linkage disequilibrium. In the asthma group, GA/AA genotypes at ATG5 -335G>A were associated with higher neutrophil counts in sputum (p < 0.05); CC/TT genotype at ATG5 8830C>T associated with lower FEV1% predicted value (p < 0.05). DNA fragments containing ATG5 -769T and -335G alleles had higher promoter activities compared to those with -769C and -335A in both human airway epithelial cells (A549, p < 0.01) and human mast cell (HMC-1, p < 0.001). GG and CC genotype at ATG7 -100A>G and 25108G>C were significantly associated with high serum levels of IL-8 (p < 0.05 for both variants). CONCLUSIONS: Genetic polymorphisms of ATG5 and ATG7 could contribute to neutrophilic airway inflammation in the pathogenesis of adult asthma.
Adolescent ; Adult ; Asthma/blood/*genetics/immunology/pathology ; Autophagy/*genetics ; Autophagy-Related Protein 5/*genetics ; Autophagy-Related Protein 7/*genetics ; Case-Control Studies ; Cell Line ; Female ; Gene Frequency ; Genes, Reporter ; Genetic Predisposition to Disease ; Haplotypes ; Heterozygote ; Homozygote ; Humans ; Interleukin-8/blood ; Male ; Middle Aged ; Neutrophil Infiltration/*genetics ; Neutrophils/immunology/metabolism/*pathology ; Phenotype ; *Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Risk Factors ; Severity of Illness Index ; Transfection ; Young Adult

PURPOSE: Toll-like receptor 3 (TLR3) recognizes to viral double-stranded RNA and is involved in antiviral defenses. A probable role of TLR3 gene variants in the pathogenesis of aspirin-intolerant asthma (AIA) has been suggested. AIA patients present more frequent asthma exacerbations in which respiratory viral infections could be an exacerbating factor. IgG subclass deficiency was commonly present with bronchial asthma. Based on previous findings, we investigated whether TLR3 variants could affect IgG3 subclass deficiency in AIA. METHODS: We enrolled 279 AIA patients, 403 aspirin-tolerant asthma (ATA) patients, and 315 normal healthy controls (NC) in this study. TLR3 polymorphism at the promoter region -299698G>T was genotyped. The serum levels of IgG subclasses were determined by the single radial immunodiffusion method. Expressions of IgG3 and TLR3 on Epstein-Barr virus transformed-B cells isolated from asthmatic patients were evaluated by flow cytometry to investigate B-cell functions. RESULTS: The TLR3 -299698 T allele was significantly associated with severity and IgG3 deficiency in the AIA group (P=0.044 and P=0.010, respectively), but not in the ATA group. IgG3 expression on B cells from asthmatics with IgG3 deficiency was significantly lower compared to those without (P=0.025). There was a positive correlation between IgG3 expression levels on B cells and serum IgG3 levels (r 2=0.434, P=0.002). CONCLUSION: These results suggest that the TLR3 -299698G>T polymorphism may be associated with IgG3 subclass deficiency and severity in AIA.
Alleles ; Asthma* ; B-Lymphocytes ; Flow Cytometry ; Herpesvirus 4, Human ; Humans ; Immunodiffusion ; Immunoglobulin G* ; Methods ; Polymorphism, Genetic ; Promoter Regions, Genetic ; RNA, Double-Stranded ; Toll-Like Receptor 3

PURPOSE: Neutrophils are considered key effector cells in the pathogenic mechanisms of airway inflammation in asthma. This study assessed the activation status of neutrophils in adult asthmatics, and the therapeutic potential of FTY720, a synthetic sphingosine-1-phosphate analog, on activated neutrophils using an in vitro stimulation model. METHODS: We isolated peripheral blood neutrophils (PBNs) from 59 asthmatic patients (including 20 aspirin-exacerbated respiratory disease [AERD] and 39 aspirin-tolerant asthma [ATA] groups). PBNs were stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or lipopolysaccharide (LPS) and their activation status was determined based on reactive oxygen species (ROS) production, cell surface expression of CD11b, interleukin (IL)-8 and matrix metallopeptidase (MMP)-9 release. PBNs were primed with FTY720 to evaluate its anti-inflammatory action. RESULTS: In vitro PBN stimulation with fMLP or LPS induced a significant increase in ROS/CD11b/IL-8/MMP-9 levels (P < 0.05 for all). In asthmatics, fMLP-induced ROS level was significantly correlated with values of forced expiratory volume in 1 second/forced vital capacity (r = −0.278; P = 0.036), maximal mid-expiratory flow (r = −0.309; P = 0.019) and PC20 methacholine (r = −0.302; P = 0.029). In addition, ROS levels were significantly higher in patients with AERD and in those with severe asthma than in those with ATA or non-severe asthma (P < 0.05 for all). FTY720 treatment could suppress ROS/CD11b levels, and LPS-induced IL-8 and MMP-9 levels (P < 0.05 for all). Responders to FTY720 treatment had significantly higher neutrophil counts in sputum (P = 0.004). CONCLUSIONS: Our findings suggest a useful in vitro PBN stimulation model for evaluating the neutrophil functional status and the therapeutic potentials of neutrophil-targeting candidates in asthmatics.
Adult ; Asthma ; Fingolimod Hydrochloride ; Forced Expiratory Volume ; Humans ; In Vitro Techniques ; Inflammation ; Interleukin-8 ; Interleukins ; Methacholine Chloride ; N-Formylmethionine Leucyl-Phenylalanine ; Neutrophil Activation ; Neutrophils ; Phenotype ; Reactive Oxygen Species ; Sputum ; Vital Capacity

Strongyloidiasis, a chronic helminth infection caused by the parasitic nematode Strongyloides stercoralis, has various clinical manifestations. Although rare, duodenal obstructions and venous thromboembolism are possible complications of strongyloidiasis.This paper presents the case of a 47-year-old Vietnamese male with a history of right lower limb edema, anorexia, nausea, vomiting, diarrhea, and abdominal discomfort lasting for four months. Venous Doppler ultrasound detected a thrombus in the right femoral vein, while an abdominal CT scan revealed a mass lesion suggestive of a lower bile duct tumor. Esophageogastroduodenoscopy showed a friable duodenal cap mucosa with multiple ulcers and edematous mucosa of the second part of the duodenum that caused a partial lumen obstruction. The final histological examination of the biopsy specimen revealed chronic duodenitis with larvae consistent with Strongyloides stercoralis. The patient was treated with Ivermectin for two weeks and anticoagulation therapy for three months. After treatment and a six-month follow-up, the patient's gastrointestinal symptoms and leg swelling resolved completely. This is the first documented case of a patient in Vietnam with strongyloidiasis who presented with venous thromboembolism and duodenal obstruction. (Korean J Gastroenterol 2023;81:270-275)

Toxocariasis, a zoonotic infection transmitted by Toxocara canis (from dogs) and Toxocara cati (from cats) larvae, poses rare but severe risks to humans. We present a case of hepatic visceral larva migrans (VLM) caused by Toxocara canis in a 21-year-old male with a history of close contact with a pet dog. Initial symptoms and imaging findings mimicked a pyogenic liver abscess. The initial laboratory investigations revealed neutrophilia and elevated levels of IgE. Despite broad-spectrum antibiotics, persistent fever prompted further investigation. Subsequent serological testing for Toxocara antibodies and histopathological analysis of liver tissue demonstrating eosinophil infiltrates and Charcot-Leyden crystals led to a confirmed diagnosis of a liver abscess caused by Toxocara canis. Serological testing for Toxocara antibodies and histopathological analysis of liver tissue confirmed a Toxocara canis-induced liver abscess. Albendazole treatment yielded significant clinical improvement. This case highlights the necessity of considering toxocariasis in liver abscess differentials, particularly in high-seroprevalence regions like Vietnam. Relying solely on serological tests may be insufficient, emphasizing the need for corroborative evidence, including invasive procedures like liver biopsy, for accurate hepatic toxocariasis diagnosis.

Purpose: Although some immune protection from close contact with individuals who have coronavirus disease 2019 (COVID-19) has been documented, there is limited data on the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals who were in lockdown with confirmed COVID-19 cases. This study investigated immunogenicity against SARS-CoV-2 in household members and people who lived near home-quarantined patients with COVID-19. Materials and Methods: This cross-sectional study was conducted during the community-based care that took place during lockdowns in District 10, Ho Chi Minh City, Vietnam from July to September 2021. SARS-CoV-2 antibody levels were determined in index cases of COVID-19, household contacts, and a no-contact group from the same area. Results: A total of 770 participants were included (355 index cases, 103 household contacts, and 312 no contacts). All index cases were unvaccinated, but >90% of individuals in the household and no-contact groups had received ≥1 vaccine dose. SARS-CoV-2 neutralizing antibodies (Nabs) were present in >77% of unvaccinated index cases versus 64%/65.4% in the householdo-contact groups (p=0.001). Antibody concentrations in unvaccinated index cases were significantly higher than those in household contacts and no contacts, with no difference between the latter groups. In all cases, antibody levels declined markedly ≥6 weeks after infection, and failed to persist beyond this time in the household and no-contact groups. Conclusion Community-based care may have helped to create community immunogenicity, but Nabs did not persist, highlighting a need for vaccination for all individuals before, or from 6 weeks after, infection with SARS-CoV-2.