RESUMO
OBJECTIVE: Coronavirus disease 2019 (COVID-19) has elevated mortality in severe and critical patients globally. This study examined the effect of glucocorticoids (GCS) on the time of virus clearance and absorption of lung lesions in severe and critical COVID-19 patients. PATIENTS AND METHODS: Severe and critical COVID-19 cases diagnosed in Wuhan Pulmonary Hospital from January 7 to February 10, 2020 were analyzed. The generalized linear model was utilized to assess the effects of GCS therapy on the times of nucleic acid test turning negative and improved pulmonary imaging, respectively. RESULTS: Of 66 patients, 51 (77.3%) and 15 (22.7%) were severe and critical cases, respectively, and aged 62 ± 11 years. A total of 58 patients (87.9%) tested negative, and 56 (84.8%) showed improved lung imaging. Age, thrombocytopenia, CD8 + T cell count, course of GCS therapy, and total dose were correlated with the time of nucleic acid test turning negative (p < 0.05), and sex was correlated with the time of initial pulmonary imaging improvement (p < 0.05). The time of nucleic acid test turning negative in individuals with GCS therapy course ≤ 10 days was shorter than that of the GCS therapy course > 10 days group (p=0.001). No statistical difference was found in the dose, course of GCS, and initial time of improved lung imaging. CONCLUSIONS: Increasing the dose of GCS and prolonging the course of treatment do not shorten the time of nucleic acid test turning negative or improved absorption of pulmonary lesions. Thus, the rational use of GCS is particularly important.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19/diagnóstico por imagem , Estado Terminal/terapia , Glucocorticoides/administração & dosagem , Índice de Gravidade de Doença , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIM: To assess the value of quantitative spleen and liver volume changes in predicting the survival of patients with primary sclerosing cholangitis (PSC). MATERIALS AND METHODS: This institutional review board-approved single-centre study included 89 PSC patients with baseline and follow-up liver imaging studies and laboratory data between 2000 and 2018. Change in spleen, total and lobar liver volumes, and lobar-to-total liver volume ratio was compared between patients with and without adverse outcome (liver transplantation, transplant waiting list, and death). Receiver operating characteristic (ROC) and Kaplan-Meier analysis were performed to identify the volumetric threshold for prediction of outcome and show how these thresholds predict survival, respectively. A p-value of <0.05 was considered statistically significant. RESULTS: The present cohort included 53 men (60%), with mean age of 42 years at baseline. The only volumetric parameters with significant differences in change between patients with and without adverse outcome were spleen volume (p<0.001) and left-to-total liver volume ratio (L/T; p=0.025). The probability of transplant-free survival at 36 months was 59.1% versus 11.9% for patients with spleen volume change <50 ml versus ≥50 ml, respectively (AUC=0.731); and 61.3% versus 13.8% for patients with L/T change <0.04 versus ≥0.04, respectively (AUC=0.638). The patients with changes below the cut-off in both spleen volume and L/T, had a higher probability of transplant-free survival at 36 months (76.8%), compared to those with change at or below the cut-offs in one or both of these two parameters (36.7%, 15%, respectively; p=0.001). CONCLUSION: Spleen volume change and L/T change might be useful biomarkers for prediction of transplant-free survival in patients with PSC.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Colangiopancreatografia por Ressonância Magnética , Colangite Esclerosante/diagnóstico por imagem , Hepatopatias/diagnóstico por imagem , Esplenopatias/diagnóstico por imagem , Adulto , Colangite Esclerosante/mortalidade , Feminino , Humanos , Hepatopatias/mortalidade , Masculino , Tamanho do Órgão , Valor Preditivo dos Testes , Esplenopatias/mortalidade , Taxa de SobrevidaRESUMO
BACKGROUND: Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID). It is characterized by heterogeneous clinical manifestations and defects in B cells and T cells. In the present study, we investigated helper T (TH) cell subsets and regulatory T (Treg) cells and their related cytokines and transcription factors in CVID patients with no definitive genetic diagnosis. METHODS: The study population comprised 13 CVID patients and 13 healthy controls. Mutation analysis was performed using whole exome sequencing in CVID patients to rule out monogenic PIDs. TH subsets and Treg were analyzed using flow cytometry. The expression of determinant cytokines (IFN-γ, IL-17, IL-22, and IL-10) and cell subset specific transcription factors was evaluated before and after stimulation. RESULTS: The main clinical presentations of these patients were infections only and lymphoproliferative phenotypes. No autoimmune or allergy phenotypes were recorded. The frequencies of CD4+ T cells, TH17, and Treg cells were significantly reduced in CVID patients; however, TH1, TH1-like TH17, and TH22 subsets were normal. After stimulation, expression of retinoic-acid-orphan-receptor-C (RORC), runtrelated transcription factor 1 (RUNX1), IL17, and IL10 was significantly lower in CVID patients than in the healthy controls. Moreover, the concentration of IL-17 and IL-10 in the cell culture supernatants of stimulated CD4+ T cells was lower in CVID patients than in healthy controls. CONCLUSIONS: Our findings demonstrate that the imbalance of TH17 and Tregs could be associated with infection and the lymphoproliferative phenotype in CVID patients without monogenic disorders.
Assuntos
Imunodeficiência de Variável Comum/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Circulação Sanguínea , Células Cultivadas , Criança , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Ativação Linfocitária , Masculino , Proteínas do Leite , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Adulto JovemRESUMO
Primary immunodeficiency disorders (PIDs) are caused by 1 or more defects of the immune system. Patients are more likely to experience recurrent and/or severe infections and tend to develop a wide range of complications. Respiratory diseases are the main and initial manifestation in most cases and the most common complication. Pulmonary complications cause significant morbidity and mortality in patients with PIDs. Early diagnosis and appropriate treatment can prevent or at least slow the development of respiratory complications. Since the spectrum of pulmonary complications in PIDs is broad, we divided pulmonary complications into upper respiratory complications (eg, sinusitis, otitis media, and laryngeal angioedema) and lower respiratory complications (eg, pneumonia, bronchitis, bronchiectasis, interstitial lung diseases, organizing pneumonia, pulmonary adenopathies and malignancies, hyperreactive airway diseases, pulmonary dysgenesis, and adverse reactions to treatment). This review covers the main respiratory manifestations in patients with PIDs.
Assuntos
Infecções Bacterianas/etiologia , Síndromes de Imunodeficiência/complicações , Doenças Respiratórias/etiologia , Angioedema/etiologia , Bronquiectasia/etiologia , Bronquite/etiologia , Pneumonia em Organização Criptogênica/etiologia , Humanos , Edema Laríngeo/etiologia , Doenças Pulmonares Intersticiais/etiologia , Neoplasias Pulmonares/etiologia , Otite Média/etiologia , Pneumonia/etiologia , Sinusite/etiologiaRESUMO
Common variable immunodeficiency (CVID) is a diagnostic category of primary immunodeficiency (PID) which may present with heterogeneous disorders including recurrent infections, autoimmunity, granulomatous diseases, lymphoid and other types of malignancies. Generally, the incidence of malignancy in CVID patients is around 1.5-20.7% and usually occurs during the 4th-6th decade of life. Non-Hodgkin lymphoma is the most frequent malignancy, followed by epithelial tumours of stomach, breast, bladder and cervix. The exact pathological mechanisms for cancer development in CVID are not fully determined; however, several mechanisms including impaired genetic stability, genetic predisposition, immune dysregulation, impaired clearance of oncogenic viruses and bacterial infections, and iatrogenic causes have been proposed to contribute to the high susceptibility of these patients to malignancies.
Assuntos
Imunodeficiência de Variável Comum/epidemiologia , Sistema Imunitário , Neoplasias/epidemiologia , Fatores Etários , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/fisiopatologia , Interação Gene-Ambiente , Predisposição Genética para Doença , Homeostase , Humanos , Incidência , Neoplasias/complicações , Neoplasias/fisiopatologiaRESUMO
Common variable immunodeficiency (CVID) is the most symptomatic primary antibody deficiency associated with recurrent infections and chronic inflammatory diseases as well as autoimmunity. CD4(+) CD25(+) FOXP3(+) regulatory T cells (Tregs) are critical T cell subsets for maintaining self-tolerance and regulation of immune response to antigens thus play a pivotal role in preventing autoimmunity. Thirty-seven CVID patients and 18 age-/sex-matched controls were enrolled. Peripheral blood mononuclear cells (PBMCs) were obtained from both groups, and the percentage of Tregs was calculated using flow cytometry method. The mRNA expression of Tregs' surface markers cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and glucocorticoid-induced tumour necrosis factor receptor (GITR), which are associated with Tregs' inhibitory function, was compared between patients and controls by quantitative real-time PCR TaqMan method. The results revealed that the frequency of Tregs was significantly lower in CVID patients than normal individuals (P < 0.001). In addition, CVID patients with autoimmunity were found to have markedly reduced proportion of Tregs compared to those cases without autoimmune diseases (P = 0.023). A significant difference was seen in factor forkhead box P3 (FOXP3) expression between CVID patients and controls (P < 0.001). The mRNAs of CTLA-4 and GITR genes were expressed at lower levels in CVID patients compared to control group (P = 0.005 and <0.001, respectively). Our findings showed reduced proportion of Tregs in CVID patients together with downregulation of FOXP3 protein and diminished expression of inhibitory Tregs' markers. It could be concluded that all of these changes may be responsible for cellular immune dysregulation observed in these patients especially those with autoimmune manifestation.