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1.
Nutrients ; 13(7)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202697

RESUMO

COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome [ARDS]/Extracorporeal membrane oxygenation [ECMO]), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 [1.01-30.26]; p = 0.048) and mortality (OR 5.21 [1.06-25.5], p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality.


Assuntos
COVID-19/sangue , Vitamina A/sangue , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , COVID-19/mortalidade , Cromatografia Líquida/métodos , Estado Terminal , Estudos Transversais , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Ferritinas/sangue , Hospitalização , Humanos , Inflamação/epidemiologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Síndrome do Desconforto Respiratório/epidemiologia , SARS-CoV-2 , Índice de Gravidade de Doença
2.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208396

RESUMO

Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer death worldwide. Recently, targeting molecules whose functions are associated with tumorigenesis has become a game changing adjunct to standard anti-cancer therapy. As evidenced by the results of preclinical and clinical investigations, whole-body irradiations (WBI) with X-rays at less than 0.1-0.2 Gy per fraction can induce remissions of various neoplasms without inciting adverse side effects of conventional chemo- and radiotherapy. In the present study, a murine model of human NSCLC was employed to evaluate for the first time the anti-neoplastic efficacy of WBI combined with inactivation of CTLA-4, PD-1, and/or HSP90. The results indicate that WBI alone and in conjunction with the inhibition of the function of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) and the programmed death-1 (PD-1) receptor immune checkpoints (ICs) and/or heat shock protein 90 (HSP90) markedly reduced tumorigenesis in mice implanted by three different routes with the syngeneic Lewis lung cancer cells and suppressed clonogenic potential of Lewis lung carcinoma (LLC1) cells in vitro. These results were associated with the relevant changes in the profile of pro- and anti-neoplastic immune cells recruited to the growing tumors and the circulating anti- and pro-inflammatory cytokines. In contrast, inhibition of the tested molecular targets used either separately or in combination with each other did not exert notable anti-neoplastic effects. Moreover, no significant synergistic effects were detected when the inhibitors were applied concurrently with WBI. The obtained results supplemented with further mechanistic explanations provided by future investigations will help design the effective strategies of treatment of lung and other cancers based on inactivation of the immune checkpoint and/or heat shock molecules combined with low-dose radiotherapy.


Assuntos
Proteínas de Choque Térmico/metabolismo , Proteínas de Checkpoint Imunológico/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Transplante de Neoplasias , Dosagem Radioterapêutica , Irradiação Corporal Total , Animais , Células Clonais , Pulmão/patologia , Contagem de Linfócitos , Linfócitos do Interstício Tumoral , Macrófagos/patologia , Camundongos Endogâmicos C57BL , Ensaio Tumoral de Célula-Tronco
3.
BMC Infect Dis ; 21(1): 666, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238240

RESUMO

BACKGROUND: This study was performed to investigate clinical features of patients with severe SARS-CoV-2 pneumonia and identify risk factors for converting to severe cases in those who had mild to moderate diseases at the start of the pandemic in China. METHODS: In this retrospective, multicenter cohort study, patients with mild to moderate SARS-CoV-2 pneumonia were included. Demographic data, symptoms, laboratory values, and clinical outcomes were collected. Data were compared between non-severe and severe patients. RESULTS: 58 patients were included in the final analysis. Compared with non-severe cases, severe patients with SARS-CoV-2 pneumonia had a longer: time to clinical recovery (12·9 ± 4·4 vs 8·3 ± 4·7; P = 0·0011), duration of viral shedding (15·7 ± 6·7 vs 11·8 ± 5·0; P = 0·0183), and hospital stay (20·7 ± 1·2 vs 14·4 ± 4·3; P = 0·0211). Multivariate logistic regression indicated that lymphocyte count was significantly associated with the rate of converting to severe cases (odds ratio 1·28, 95%CI 1·06-1·54, per 0·1 ×  109/L reduced; P = 0·007), while using of low-to-moderate doses of systematic corticosteroids was associated with reduced likelihood of converting to a severe case (odds ratio 0·14, 95%CI 0·02-0·80; P = 0·0275). CONCLUSIONS: The low peripheral blood lymphocyte count was an independent risk factor for SARS-CoV-2 pneumonia patients converting to severe cases. However, this study was carried out right after the start of the pandemic with small sample size. Further prospective studies are warranted to confirm these findings. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000029839 . Registered 15 February 2020 - Retrospectively registered.


Assuntos
COVID-19/diagnóstico , COVID-19/fisiopatologia , Corticosteroides/administração & dosagem , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/virologia , China/epidemiologia , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/patogenicidade , Tamanho da Amostra , Eliminação de Partículas Virais
4.
BMC Infect Dis ; 21(1): 631, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210280

RESUMO

BACKGROUND: COVID-19 continuously threated public health heavily. Present study aimed to investigate the lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients. METHODS: Lymphocyte subsets was classified using flow cytometry with peripheral blood collected from 106 patients. RESULTS: Multivariate logistic regression showed that chest tightness, lymphocyte count, and γ-glutamyl transpeptidase were the independent predictors for severe COVID-19. The T cell, CD4+ T cell and B cell counts in severe patients were significantly lower than that in mild patients (p = 0.004, 0.003 and 0.046, respectively). Only the T cell count was gradually decreased with the increase of infiltrated quadrants of lesions in computed tomography (CT) (p = 0.043). The T cell, CD4+ T cell, and CD8+ T cell counts were gradually decreased with the increase of infiltrated area of the maximum lesion in CT (p = 0.002, 0.003, 0.028; respectively). For severe patients, the counts of T cell, CD4+ T cell, CD8+ T cell gradually decreased with the increased delayed hospitalization (p = 0.001, 0.03, and <  0.001, respectively). The proportions of T cell, CD8+ T cell gradually decreased with the increased delayed hospitalization (both p <  0.001), but the proportions of NK cell, B cell gradually increased with the increased delayed hospitalization (p = 0.007, and 0.002, respectively). For mild patients, only the NK cell count was gradually decreased with the increased delayed hospitalization (p = 0.012). CONCLUSION: T lymphocyte and its subset negatively correlated with disease severity, CT manifestation and delayed hospitalization. The counts of lymphocyte subset were changed more profound than their proportions.


Assuntos
COVID-19/diagnóstico por imagem , COVID-19/patologia , Subpopulações de Linfócitos , SARS-CoV-2 , Adulto , Linfócitos B , Testes Diagnósticos de Rotina , Citometria de Fluxo , Hospitalização , Humanos , Células Matadoras Naturais , Modelos Logísticos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
5.
Anticancer Res ; 41(7): 3625-3634, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230159

RESUMO

BACKGROUND/AIM: Stage III breast cancer comprises a broad spectrum of disease, including the extent of supraclavicular/internal mammary lymph node metastasis. In this study, we evaluated the usefulness of the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of patients with stage III breast cancer. PATIENTS AND METHODS: Seventy-five patients with stage III breast cancer who underwent surgery were included. We compared their clinicopathological factors according to the presence or not of supraclavicular/internal mammary lymph node metastasis, and pretreatment ALC or NLR. RESULTS: Patients with metastasis of the studied lymph nodes had a poorer prognosis in comparison to those without metastasis. In patients without these types of lymph node metastasis, both the ALC and NLR were predictive factors for relapse-free and overall survival. Among these patients, those with a low ALC or high NLR had recurrence-free and overall survival comparable to those of patients with supraclavicular/internal mammary lymph node metastasis. CONCLUSION: Pretreatment ALC and NLR were prognostic factors for patients with stage III breast cancer.


Assuntos
Neoplasias da Mama/patologia , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Contagem de Linfócitos/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico
6.
J Int Med Res ; 49(7): 3000605211030124, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34250826

RESUMO

BACKGROUND: Anemia can negatively affect the outcome of many diseases, including infections and inflammatory conditions. AIM: To compare the prognostic value of hemoglobin level and the neutrophil/lymphocyte ratio (NLR) for prediction of coronavirus disease 2019 (COVID-19) severity. METHODS: In this retrospective cohort study, clinical data from patients with laboratory-confirmed COVID-19 were collected from hospital records from 10 April 2020 to 30 July 2020. RESULTS: The proportions of patients with mild, moderate, and severe COVID-19 differed significantly in association with hemoglobin levels, neutrophil counts, lymphocyte counts, NLR, and total leukocyte counts. Patients with severe COVID-19 had significantly lower hemoglobin levels than those with moderate or mild COVID-19. There were statistically significant negative associations between hemoglobin and D-dimer, age, and creatinine. The optimal hemoglobin cut-off value for prediction of disease severity was 11.6 g/dL. Using this cut-off value, hemoglobin had higher negative predictive value and sensitivity than NLR (92.4% and 51.3%, respectively). The specificity of hemoglobin as a prognostic marker was 79.3%. CONCLUSION: Both NLR and hemoglobin level are of prognostic value for predicting severity of COVID-19. However, hemoglobin level displayed higher sensitivity than NLR. Hemoglobin level should be assessed upon admission in all patients and closely monitored throughout the disease course.


Assuntos
COVID-19 , Neutrófilos , Humanos , Contagem de Linfócitos , Linfócitos , Prognóstico , Curva ROC , Estudos Retrospectivos , SARS-CoV-2
7.
Medicine (Baltimore) ; 100(28): e26503, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260527

RESUMO

ABSTRACT: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading on a global scale and poses a great threat to human health. However, efficient indicators for disease severity have not been fully investigated. Here, we aim to investigate whether dynamic changes of lymphocyte counts can predict the deterioration of patients with COVID-19.We collected data from 2923 patients with laboratory-confirmed COVID-19. Patients were then screened, and we focused on 145 severe cases and 60 critical cases (29 recovered cases, 31 deaths). The length of hospitalization was divided into five time points, namely admission, 25%, 50%, 75% and discharge or death, according to the principle of interquartile distance. A series of laboratory findings and clinical data were collected and analyzed during hospitalization. The results showed that there were differences in levels of leukocytes, neutrophils and lymphocytes at almost every time point in the severe cases and 60 critical cases (29 recovered cases, 31 deaths). Further analysis showed that 70.2% of the COVID-19 cases had low circulating lymphocyte count, of which 64.1% were severe cases and 85.0% were critical cases (75.9% recovered cases and 93.5% died). Moreover, the lymphocyte count in dead cases was significantly lower than that of critical cases who recovered, at almost every time point in the critical groups. We also divided critical patients into group A (<1.1 × 109/L) and group B (>1.1 × 109/L) according to number of lymphocytes. Through survival analysis, we found that there was no significant difference in survival between group A and group B at admission (P = .3065). However, the survival rate according to lymphocyte levels in group A was significantly lower than that of group B at 25% hospital stay (on average day 6.5), 50% and 75% time points (P < .001).Lymphocyte counts that remain lower after the first week following symptom onset are highly predictive of in-hospital death of adults with COVID-19. This predictor may help clinicians identify patients with a poor prognosis and may be useful for guiding clinical decision-making at an early stage.


Assuntos
COVID-19/sangue , COVID-19/mortalidade , Contagem de Linfócitos/estatística & dados numéricos , Linfócitos/metabolismo , SARS-CoV-2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/virologia , Feminino , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
8.
J Coll Physicians Surg Pak ; 30(7): 821-824, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34271783

RESUMO

OBJECTIVE: To determine the predictive significance of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in early-onset neonatal sepsis (EONS). STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: The Neonatal Intensive Care Unit (NICU), Affiliated Hospital of Yanbian University, Jilin, China, from January 2018 to January 2020. METHODOLOGY: Of the total 124 children, 74 children with EONS were enrolled in group A and 50 children without infection-related diseases were enrolled in group B (control). The EONS risk factors were evaluated by logistic regression. Besides, the PLR and NLR diagnostic performances in EONS were evaluated by plotting the receiving operating characteristic (ROC) curves. RESULTS: In the univariate analysis, the differences for platelet count, lymphocyte number, neutrophil number, NLR, and PLR, between group A and group B were of statistical significance (p = 0.02, 0.021, <0.001, <0.001, and <0.001 respectively). As suggested by logistic regression, PLR and NLR were identified as the factors to independently predict the risk of EONS (p = 0.012, and 0.003, respectively). In addition, the value of area under the ROC curve (AUC) of NLR in predicting EONS was 0.788 (95% CI: 0.708-0.868; p <0.001), which was greater than that of PLR. At the NLR value of ≥3.169, the sensitivity of predicting EONS was 77%, and the specificity was 78%. CONCLUSION: Peripheral blood NLR and PLR have high predictive value for EONS. The predictive value of NLR as a biomarker for EONS evaluation was greater than that of PLR. Key Words: Neonatal sepsis, Logistic models, ROC curve, Blood cell count.


Assuntos
Sepse Neonatal , Neutrófilos , Biomarcadores , Plaquetas , Criança , China , Humanos , Recém-Nascido , Contagem de Linfócitos , Linfócitos , Prognóstico , Curva ROC , Estudos Retrospectivos
9.
Artigo em Inglês | MEDLINE | ID: mdl-34261812

RESUMO

OBJECTIVE: To evaluate the clinical consequences of extended interval dosing (EID) of ocrelizumab in relapsing-remitting multiple sclerosis (RRMS) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In our retrospective, multicenter cohort study, we compared patients with RRMS on EID (defined as ≥4-week delay of dose interval) with a control group on standard interval dosing (SID) at the same period (January to December 2020). RESULTS: Three hundred eighteen patients with RRMS were longitudinally evaluated in 5 German centers. One hundred sixteen patients received ocrelizumab on EID (median delay [interquartile range 8.68 [5.09-13.07] weeks). Three months after the last ocrelizumab infusion, 182 (90.1%) patients following SID and 105 (90.5%) EID patients remained relapse free (p = 0.903). Three-month confirmed progression of disability was observed in 18 SID patients (8.9%) and 11 EID patients (9.5%, p = 0.433). MRI progression was documented in 9 SID patients (4.5%) and 8 EID patients (6.9%) at 3-month follow-up (p = 0.232). Multivariate logistic regression showed no association between treatment regimen and no evidence of disease activity status at follow-up (OR: 1.266 [95% CI: 0.695-2.305]; p = 0.441). Clinical stability was accompanied by persistent peripheral CD19+ B-cell depletion in both groups (SID vs EID: 82.6% vs 83.3%, p = 0.463). Disease activity in our cohort was not associated with CD19+ B-cell repopulation. CONCLUSION: Our data support EID of ocrelizumab as potential risk mitigation strategy in times of the COVID-19 pandemic. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RRMS, an EID of at least 4 weeks does not diminish effectiveness of ocrelizumab.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/complicações , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Antígenos CD19 , Linfócitos B/imunologia , Avaliação da Deficiência , Feminino , Humanos , Contagem de Linfócitos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Resultado do Tratamento
10.
J Int Soc Sports Nutr ; 18(1): 57, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271953

RESUMO

BACKGROUND: This paper aimed to verify how a supplementation of rower's diet with Astragalus Membranaceus Root (AMR) modulated their immune system response to maximal physical exertion. METHODS: The double-blind study included 18 members of the Polish Rowing Team assigned to the supplemented group (n = 10), and the placebo group (n = 8). The participants performed a 2000 m test on a rowing ergometer at the beginning and at the end of the six-week of intensive training camp during which the supplemented group received 500 mg of AMR. Blood samples were obtained prior to, 1 min after completing, and 24 h after the exertion test. The levels of interleukin 2 (IL2), interleukin 4 (IL4), interleukin 10 (IL10), interferon ɤ (IFN-É£), and lactic acid were determined. Subpopulations of T regulatory lymphocytes [CD4+/CD25+/CD127-] (Treg), cytotoxic lymphocytes [CD8+/TCRαß+] (CTL), natural killer cells [CD3-/CD16+/CD56+] (NK), and TCRδγ-positive cells (Tδγ) were determined with flow cytometry. RESULTS: After the camp, the initial NK and Treg levels sustained at the baseline, while Tδγ counts increased relative to the levels in the placebo group. In the supplemented subgroup, a decrease in IL2 level in reaction to maximal exertion clearly deepened while the change in IL-2/IL-10 level induced by the recovery after this exertion clearly increased, relative to the changes in the placebo group. CONCLUSIONS: AMR restored the immunological balance in strenuously trained athlets through a stabilization of NK and Treg cells with a positive trend in Tδγ towards Th1 response during restitution by cytokine IL2 modulation.


Assuntos
Medicamentos de Ervas Chinesas/química , Exercício Físico/fisiologia , Tolerância Imunológica/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Esportes Aquáticos/fisiologia , Método Duplo-Cego , Humanos , Interleucina-4 , Interleucinas/sangue , Células Matadoras Naturais , Contagem de Linfócitos , Masculino , Receptores de Antígenos de Linfócitos T gama-delta , Linfócitos T Reguladores , Adulto Jovem
11.
Front Public Health ; 9: 664108, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211953

RESUMO

COVID-19 may appear with a widely heterogeneous clinical expression. Thus, predictive markers of the outcome/progression are of paramount relevance. The neutrophil/lymphocyte ratio (NLR) has been suggested as a good predictive marker of disease severity and mortality. Accordingly, we found that NLR significantly increased in parallel with the WHO severity stage in COVID-19 patients during the Ist wave (March-May 2020; n = 49), due to the significant reduction of lymphocyte and the significant increase of neutrophil in severe COVID-19 patients. While, we did not observe significant differences of NLR between the WHO severity stage among COVID-19 patients of the IInd wave (September 2020-April 2021; n = 242). In these patients, the number of lymphocytes and neutrophils did not change significantly between patients of different severity subgroups. This difference likely depends on the steroids therapy that the patients of the IInd wave performed before hospitalization while most patients of the Ist wave were hospitalized soon after diagnosis. This is also confirmed by serum interleukin (IL)-6 and myeloperoxidase (MPO) that gradually increased with the disease stage in patients of the Ist wave, while such biomarkers (whose production is inhibited by steroids) did not show differences among patients of the IInd wave in different stages. Thus, the NLR could be tested at diagnosis in naïve patients before starting therapies.


Assuntos
COVID-19 , Neutrófilos , Humanos , Contagem de Linfócitos , Linfócitos , Prognóstico , Estudos Retrospectivos , SARS-CoV-2
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 781-786, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105472

RESUMO

OBJECTIVE: To explore the influence of controlling nutritional status (CONUT) score on the prognosis of newly diagnosed patients with multiple myeloma (MM). METHODS: The clinical data 119 patients with MM who were diagnosed according to the international myeloma diagnostic criteria in Lanzhou University Second Hospital from April 2010 to October 2018 were collected and retrospectively analyzed. The relationship between clinical indexes, including age, sex, MM type, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), absolute monocyte count (AMC), hemoglobin (Hb), platelet (PLT), ß2-microglobulin (ß2-MG), lactate dehydrogenase (LDH), albumin (ALB), globulin (GLO), cholesterol (CHO), serum creatinine (Scr), etc, and CONUT score was discussed to explore the prognostic value of these indicators. SPSS 25.0 software was used for statistical analysis. Progression-free survival(PFS) and overall survival (OS) between different subgroups were calculated by Kaplan-Meier curves and difference between survival curves was detected by Log-rank tests. Receiver operating characteristic (ROC) curve was used to estimate the most discriminative cutoff value of CONUT score for predicting OS. Mann-Whitney U test was used for non-parametric samples, and chi-square test for categorical variables. Univariate and multivariate analysis were performed by using COX proportional hazards model to identify factors associated with OS. RESULTS: Compared with high-scoring group, low-scoring group had a better OS ï¼»median OS was 43.3 months and 127.67 months, respectively, 95% confidence interval (CI): 57.065-78.345, P=0.038ï¼½. At the same time, the low-scoring group also had higher level of ALC, ANC, AMC, Hb, PLT, ALB, and CHO but lower of GLO. Multivariate survival analysis showed that age (HR=1.027, 95%CI: 1.000-1.054, P=0.048), AMC (HR=11.284, 95%CI: 22.968-42.897, P<0.001), CONUT score (HR=1.198, 95%CI: 1.036-1.385, P=0.015), M protein (non-IgG/IgG type) type (HR=0.503, 95%CI: 0.259-0.977, P=0.043) were independent factors affecting the prognosis of MM patients. CONCLUSION: The CONUT score as an immune-nutrition score is a convenient and easy-to-obtain index to effectively predict the prognosis of MM patients.


Assuntos
Mieloma Múltiplo , Humanos , Contagem de Linfócitos , Mieloma Múltiplo/diagnóstico , Estado Nutricional , Prognóstico , Estudos Retrospectivos
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 963-968, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105501

RESUMO

OBJECTIVE: To investigate the changes in function of CD8+ T cell subsets, and explore its significance in pathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH). METHODS: Flow cytometry was used to detect the expressions of PD-1, TIM-3, and LAG-3, which were the markers of exhausted CD8+ T cell, as well as the secretion levels of interferon γ (IFN-γ) and expression of ΔCD107a after the stimulation; the numbers of effector-memory CD8+ T cells, regulatory T cells and double negative T cells were also detected. RESULTS: The expressions of inhibitory receptors (PD-1, TIM3 and LAG-3) on CD8+ T cells of sHLH patients were 40.73±22.64, 15.97±14.45 and 0.73 (0-37.41), respectively, which were significantly higher than those of the control group (P<0.001). In contrast, the expression of ΔCD107a (4.49±2.71 vs 6.07±2.14, P=0.035) and secretion level of IFN-γ (37.30±24.46 vs 55.17±22.23, P=0.034) were significantly lower. The number of effector-memory CD8+ T cells in sHLH patients was also lower as compared with that in control group (14.35±10.37 vs 22.92±11.12, P=0.016). But there was no significant difference in the number of regulatory T cell and double negative T cell. In addition, the expressions of PD-1, TIM3 and LAG-3 in active stage of sHLH were 38.09±21.87, 14.35±13.70 and 0.82 (0-13.22), respectively, which were significant higher than those in remission stage [24.27±17.23 (P=0.03), 8.64±5.60 (P=0.014) and 0.13 (0-3.69)]. CONCLUSION: The exhausted CD8+ T lymphocytes may play a critical role in the development of sHLH.


Assuntos
Linfo-Histiocitose Hemofagocítica , Linfócitos T CD8-Positivos , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Interferon gama , Contagem de Linfócitos
14.
Comput Math Methods Med ; 2021: 9926249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122620

RESUMO

Objectives: This study is aimed at exploring the relationship of the viral load of coronavirus disease 2019 (COVID-19) with lymphocyte count, neutrophil count, and C-reactive protein (CRP) and investigating the dynamic change of patients' viral load during the conversion from mild COVID-19 to severe COVID-19, so as to clarify the correlation between the viral load and progression of COVID-19. Methods: This paper included 38 COVID-19 patients admitted to the First Hospital of Jiaxing from January 28, 2020, to March 6, 2020, and they were clinically classified according to the Guidelines on the Novel Coronavirus-Infected Pneumonia Diagnosis and Treatment. According to the instructions of the Nucleic Acid Detection Kit for the 2019 novel coronavirus (SARS-CoV-2), respiratory tract specimens (throat swabs) were collected from patients for nucleic acid testing. Patients' lymphocyte count and neutrophil count were determined by blood routine examination, and CRP was measured by biochemical test. Results: The results of our study suggested that the cycle threshold (Ct) value of Nucleocapsid protein (N) gene examined by nucleic acid test was markedly positively correlated with lymphocyte count (p = 0.0445, R 2 = 0.1203), but negatively correlated with neutrophil count (p = 0.0446, R 2 = 0.1167) and CRP (p = 0.0393, R 2 = 0.1261), which indicated that patients with a higher viral load tended to have lower lymphocyte count but higher neutrophil count and CRP. Additionally, we detected the dynamic change of Ct value in patients who developed into a severe case, finding that viral load of 3 patients increased before disease progression, whereas this phenomenon was not found in 2 patients with underlying diseases. Conclusion: The results of this study demonstrated that viral load of SARS-CoV-2 is significantly negatively correlated with lymphocyte count, but markedly positively correlated with neutrophil count and CRP. The rise of viral load is very likely to be the key factor leading to the overloading of the body's immune response and resulting in the disease progression into severe disease.


Assuntos
COVID-19/virologia , SARS-CoV-2 , Carga Viral , Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/imunologia , China/epidemiologia , Biologia Computacional , Proteínas do Nucleocapsídeo de Coronavírus/genética , Progressão da Doença , Genes Virais , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Neutrófilos , Pandemias , Fosfoproteínas/genética , Estudos Retrospectivos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação
15.
Int J Mol Sci ; 22(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071045

RESUMO

The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.


Assuntos
Antígeno B7-H1/biossíntese , Linfócitos T CD8-Positivos/imunologia , Carcinoma de Célula de Merkel/mortalidade , Indolamina-Pirrol 2,3,-Dioxigenase/biossíntese , Linfócitos do Interstício Tumoral/imunologia , Proteínas de Neoplasias/biossíntese , Neoplasias Cutâneas/mortalidade , Subpopulações de Linfócitos T/imunologia , Imunidade Adaptativa , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Linfócitos T CD8-Positivos/química , Carcinoma de Célula de Merkel/química , Carcinoma de Célula de Merkel/imunologia , Carcinoma de Célula de Merkel/virologia , Feminino , Fatores de Transcrição Forkhead/análise , Neoplasias de Cabeça e Pescoço/química , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Poliomavírus das Células de Merkel/isolamento & purificação , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Segunda Neoplasia Primária/química , Segunda Neoplasia Primária/imunologia , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/virologia , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Fatores Sexuais , Neoplasias Cutâneas/química , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/virologia , Úlcera Cutânea/etiologia , Infecções Tumorais por Vírus
16.
Anticancer Res ; 41(6): 3109-3119, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34083304

RESUMO

BACKGROUND/AIM: We investigated the usefulness of dynamic changes in absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) during eribulin therapy as predictive markers for survival benefit including post-progression survival (PPS). PATIENTS AND METHODS: We retrospectively investigated 94 advanced breast cancer (ABC) patients who underwent eribulin therapy between July 2011 and June 2020. RESULTS: The multivariate analysis showed that high baseline ALC and low NLR were independent predictive markers for overall survival (OS) (p=0.007 and p=0.011, respectively) and PPS (p=0.005 and p=0.007, respectively). Dynamic changes in ALC were also associated with OS and PPS (p=0.015, and p=0.026, respectively) and were an independent predictive marker for PPS (p=0.021). CONCLUSION: Baseline ALC and NLR and dynamic changes in ALC during eribulin therapy were significantly associated with survival benefit including PPS for patients with ABC.


Assuntos
Furanos/uso terapêutico , Cetonas/uso terapêutico , Contagem de Linfócitos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Humanos , Pessoa de Meia-Idade , Análise de Sobrevida
17.
Front Immunol ; 12: 568789, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149679

RESUMO

Dysregulation of immune response was observed in COVID-19 patients. Thymosin alpha 1 (Tα1) is used in the management of COVID-19, because it is known to restore the homeostasis of the immune system during infections and cancers. We aim to observe the longitudinal changes in T lymphocyte subsets and to evaluate the efficacy of Tα1 for COVID-19. A retrospective study was conducted in 275 COVID-19 patients admitted to Shanghai public health clinical center. The clinical and laboratory characteristics between patients with different T lymphocyte phenotypes and those who were and were not treated with Tα1 were compared. Among the 275 patients, 137 (49.8%) were males, and the median age was 51 years [interquartile range (IQR): 37-64]. A total of 126 patients received Tα1 therapy and 149 patients did not. There were 158 (57.5%) patients with normal baseline CD4 counts (median:631/µL, IQR: 501~762) and 117 patients (42.5%) with decreased baseline CD4 counts (median:271/µL, IQR: 201~335). In those with decreased baseline CD4 counts, more patients were older (p<0.001), presented as critically ill (p=0.032) and had hypertension (p=0.008) compared with those with normal CD4 counts. There was no statistical difference in the duration of virus shedding in the upper respiratory tract between the two groups (p=0.214). In both the normal (14 vs 11, p=0.028) and the decreased baseline CD4 counts group (15 vs 11, p=0.008), duration of virus clearance in the patients with Tα1 therapy was significantly longer than that in those without Tα1 therapy. There was no significant difference in the increase of CD4+ (286 vs 326, p=0.851) and CD8+ T cell (154 vs 170, p=0.842) counts in the recovery period between the two groups with or without Tα1 therapy. Multivariate linear regression analysis showed that severity of illness (p<0.001) and Tα1 therapy (p=0.001) were associated with virus clearance. In conclusion, reduction of CD4+ T and CD8+ T cell counts were observed in COVID-19 patients. Tα1 may have no benefit on restoring CD4+ and CD8+ T cell counts or on the virus clearance. The use of Tα1 for COVID-19 need to be more fully investigated.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , COVID-19/tratamento farmacológico , Timalfasina/uso terapêutico , Adjuvantes Imunológicos/farmacologia , Adulto , COVID-19/imunologia , China , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2
18.
Emerg Microbes Infect ; 10(1): 1156-1168, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34060982

RESUMO

ABSTRACTThe risk of secondary infection with SARS-CoV-2 and influenza A virus is becoming a practical problem that must be addressed as the flu season merges with the COVID-19 pandemic. As SARS-CoV-2 and influenza A virus have been found in patients, understanding the in vivo characteristics of the secondary infection between these two viruses is a high priority. Here, hACE2 transgenic mice were challenged with the H1N1 virus at a nonlethal dose during the convalescent stage on 7 and 14 days post SARS-CoV-2 infection, and importantly, subsequent H1N1 infection showed enhanced viral shedding and virus tissue distribution. Histopathological observation revealed an extensive pathological change in the lungs related to H1N1 infection in mice recovered from SARS-CoV-2 infection, with severe inflammation infiltration and bronchiole disruption. Moreover, upon H1N1 exposure on 7 and 14 dpi of SARS-CoV-2 infection, the lymphocyte population activated at a lower level with T cell suppressed in both PBMC and lung. These findings will be valuable for evaluating antiviral therapeutics and vaccines as well as guiding public health work.


Assuntos
Lesão Pulmonar Aguda/patologia , Enzima de Conversão de Angiotensina 2/genética , COVID-19/patologia , Infecções por Orthomyxoviridae/patologia , Lesão Pulmonar Aguda/virologia , Animais , COVID-19/terapia , Coinfecção/patologia , Coinfecção/virologia , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Pulmão/patologia , Contagem de Linfócitos , Linfócitos/imunologia , Camundongos , Camundongos Transgênicos , Infecções por Orthomyxoviridae/terapia , SARS-CoV-2/isolamento & purificação , Carga Viral , Replicação Viral/fisiologia , Eliminação de Partículas Virais/fisiologia
19.
Viruses ; 13(6)2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071557

RESUMO

Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.


Assuntos
COVID-19/imunologia , COVID-19/fisiopatologia , Cardiomiopatias/imunologia , Doença da Artéria Coronariana/imunologia , Tromboembolia Venosa/imunologia , COVID-19/complicações , COVID-19/genética , Cardiomiopatias/complicações , Cardiomiopatias/genética , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Citocinas/genética , Conjuntos de Dados como Assunto , Humanos , Hospedeiro Imunocomprometido/genética , Inflamassomos/genética , Contagem de Linfócitos , Gravidade do Paciente , RNA-Seq , Tromboembolia Venosa/complicações
20.
Am J Clin Pathol ; 156(2): 185-197, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34151348

RESUMO

OBJECTIVES: We compared complete blood count (CBC) with differential and markers of inflammation and coagulation in patients with and without coronavirus disease 2019 (COVID-19) presenting to emergency departments in Seattle, WA. METHODS: We reviewed laboratory values for 1 week following each COVID-19 test for adult patients who received a standard severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) test before April 13, 2020. Results were compared by COVID-19 status and clinical course. RESULTS: In total 1,027 patients met inclusion criteria. Patients with COVID-19 (n = 155) had lower leukocytes (P < .0001), lymphocytes (P < .0001), platelets (P < .0001), and higher hemoglobin (P = .0140) than those without, but absolute differences were small. Serum albumin was lower in patients with COVID-19 (P < .0001) and serum albumin, neutrophil to lymphocyte ratio (NLR), and red cell distribution width (RDW) were each associated with disease severity. NLR did not differ between patients with COVID-19 and those without (P = .8012). CONCLUSIONS: Patients with COVID-19 had modestly lower leukocyte, lymphocyte, and platelet counts and higher hemoglobin values than patients without COVID-19. The NLR, serum albumin, and RDW varied with disease severity, regardless of COVID-19 status.


Assuntos
Contagem de Células Sanguíneas , Coagulação Sanguínea , COVID-19/sangue , Inflamação/sangue , Linfócitos/citologia , Adulto , Biomarcadores/sangue , Contagem de Células Sanguíneas/métodos , COVID-19/diagnóstico , Serviço Hospitalar de Emergência , Humanos , Contagem de Leucócitos/métodos , Contagem de Linfócitos/métodos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Contagem de Plaquetas/métodos , SARS-CoV-2/patogenicidade
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