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1.
Int J Legal Med ; 134(6): 2205-2208, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32613447

RESUMO

"Severe acute respiratory syndrome" (SARS) due to coronavirus (SARS-CoV-2) infection is a well-known cause of death. Sometimes, demise can occur unexpectedly in apparently previous healthy individual after a brief period of trivial flu-like symptoms. In these doubtful cases, the forensic pathologist could be requested to define the cause of death occurred outside the hospital. In this report, the authors describe two autopsied cases of SARS-CoV-2-related deaths which occurred suddenly at home and were not preceded by hospitalization, highlighting associated histopathologic patterns and correlating them to pathophysiology of viral infection.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Pulmão/patologia , Pneumonia Viral/patologia , Córtex Suprarrenal/patologia , Idoso , Células Epiteliais Alveolares/patologia , Autopsia , Agregação Celular , Eosinófilos/patologia , Feminino , Humanos , Hiperplasia , Corpos de Inclusão Intranuclear/patologia , Megacariócitos/patologia , Microscopia , Pessoa de Meia-Idade , Multimorbidade , Pandemias , Embolia Pulmonar/patologia , Esplenomegalia/patologia
2.
J Cancer Res Ther ; 16(3): 581-586, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719271

RESUMO

Introduction: Eosinophils are multifunctional granulocytes, which play a pivotal role in health and disease. Tumor Associated Tissue Eosinophilia (TATE) has long been evaluated in the diagnosis and progression of oral squamous cell carcinomas (OSCCs). However, their association with Tumor Associated Blood Eosinophilia (TABE) in OSCCs is still far fetched. We, therefore, attempted to evaluate their individual roles and to achieve a ratio between TATE and TABE in order to signify its usage in objectifying the diagnosis. Materials and Methods: TATE was evaluated using H and E stain per 10 high power fields in 33 previously diagnosed cases of OSCC which were retrieved from department archives. TABE values were achieved from complete blood hemogram reports of patients. TATE/TABE ratio was calculated. All the parameters were clinicopathologically correlated and statistically evaluated using SPSS. Results: TATE represented higher values in well-differentiated squamous cell carcinoma (WDSCC) and poorly differentiated squamous cell carcinoma (PDSCC) and was least in moderately differentiated squamous cell carcinoma (MDSCC), whereas TABE linearly increased from WDSCC to PDSCC. TNM Stage II cases revealed the highest TATE and lowest TABE. TATE/TABE ratio was the highest in WDSCC. Conclusion: Due to the dual nature of eosinophils in early and late carcinogenesis events, evaluation of only TATE might not be conclusive in determining tumor grade. Hence, in a first of its kind attempt, the TATE/TABE ratio may be suitable to achieve a criterion for the determination of tumor grade and may also help to unfold the underlying biologic events.


Assuntos
Eosinofilia/patologia , Eosinófilos/patologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Eosinofilia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/sangue , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Coloração e Rotulagem/métodos
3.
J Cancer Res Ther ; 16(3): 494-499, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719256

RESUMO

Introduction: Conventional oral squamous cell carcinoma (OSCC) is relatively easy to diagnose on histopathology, as it comprises dysplastic epithelial cells with variable degrees of squamous differentiation. Different grading systems have been employed in grading OSCC based on its dysplastic features and host response. Some unusual features such as clear cell change, epithelial-mesenchymal transition (EMT), stromal hyalinization, stromal desmoplasia, perineural invasion, vascular invasion, tissue eosinophilia, giant cells, and tertiary lymphoid follicle formation are evident in OSCC histologically but have not yet been accounted in any grading systems of OSCC except perineural and vascular invasion. Aim: The aim of the present study was to identify these uncommon features and to correlate them with different grades of OSCC.Materials and Methods:This study was conducted on 100 histopathologically confirmed OSCC cases retrieved from the archives of our department. They were graded on the basis of Broder's grading system and were reviewed for the features mentioned above. Data collected were subjected to statistical analysis. Results: Clear cell change, EMT, foreign body giant cells, and tumor giant cells were observed in 13%, 20%, 1%, and 3% of cases, respectively. We found stromal desmoplasia in 15% and stromal hyalinization in 9% of cases. Tissue eosinophilia, tertiary lymphoid follicle formation, and perineural invasion were observed in 12%, 3%, and 2% of cases, respectively. Vascular invasion was not evident in any of the cases examined. Conclusion: The incidence of the unusual features was 7.8% in our study.


Assuntos
Carcinoma de Células Escamosas/patologia , Eosinófilos/patologia , Transição Epitelial-Mesenquimal , Neoplasias Bucais/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
4.
J Allergy Clin Immunol ; 146(2): 315-324.e7, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32531372

RESUMO

BACKGROUND: More than 300 million people carry a diagnosis of asthma, with data to suggest that they are at a higher risk for infection or adverse outcomes from severe acute respiratory syndrome coronavirus 2. Asthma is remarkably heterogeneous, and it is currently unclear how patient-intrinsic factors may relate to coronavirus disease 2019. OBJECTIVE: We sought to identify and characterize subsets of patients with asthma at increased risk for severe acute respiratory syndrome coronavirus 2 infection. METHODS: Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to angiotensin-converting enzyme-2 (ACE2) expression within bronchial epithelium. ACE-2-correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets. RESULTS: Stratifying by type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the severe acute respiratory syndrome coronavirus 2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with type 1 and 2 IFN signatures, normally induced by viral infections. T-cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe coronavirus disease 2019, including male sex, history of hypertension, low peripheral blood, and elevated bronchoalveolar lavage lymphocytes. CONCLUSIONS: ACE2 expression is linked to upregulation of viral response genes in a subset of type 2-low patients with asthma with characteristics resembling known risk factors for severe coronavirus disease 2019. Therapies targeting the IFN family and T-cell-activating factors may therefore be of benefit in a subset of patients.


Assuntos
Asma/epidemiologia , Asma/genética , Infecções por Coronavirus/epidemiologia , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/epidemiologia , Receptores Virais/genética , Adolescente , Adulto , Asma/classificação , Asma/imunologia , Betacoronavirus/genética , Betacoronavirus/imunologia , Biomarcadores/metabolismo , Brônquios/imunologia , Brônquios/patologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Estudos de Coortes , Infecções por Coronavirus/virologia , Eosinófilos/imunologia , Eosinófilos/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Interferon gama/genética , Interferon gama/imunologia , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/virologia , Mapeamento de Interação de Proteínas , Receptores Virais/imunologia , Fatores de Risco , Índice de Gravidade de Doença , Linfócitos T/classificação , Linfócitos T/imunologia , Linfócitos T/patologia , Transcriptoma , Estados Unidos/epidemiologia
5.
Microbes Infect ; 22(9): 403-404, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32599077

Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Síndrome Respiratória Aguda Grave/prevenção & controle , Vacinas Virais/administração & dosagem , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Eosinófilos/patologia , Eosinófilos/virologia , Humanos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/patologia , Monócitos/virologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/imunologia , Vírus Sinciciais Respiratórios/patogenicidade , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Vacinas Virais/efeitos adversos
6.
Clin Chim Acta ; 508: 122-129, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32417210

RESUMO

BACKGROUND: The underlying changes of peripheral blood inflammatory cells (PBICs) in COVID-19 patients are little known. Moreover, the risk factors for the underlying changes of PBICs and their predicting role in severe COVID-19 patients remain uncertain. MATERIAL AND METHODS: This retrospective study including two cohorts: the main cohort enrolling 45 patients of severe type serving as study group, and the secondary cohort enrolling 12 patients of no-severe type serving as control group. The PBICs analysis was based on blood routine and lymphocyte subsets. The inflammatory cell levels were compared among patients according to clinical classifications, disease-associated phases, as well as one-month outcomes. RESULTS: Compared with patients of non-severe type, the patients of severe type suffered from significantly decreased counts of lymphocytes, eosinophils, basophils, but increased counts of neutrophils. These PBICs alterations got improved in recovery phase, but persisted or got worse in aggravated phase. Compared with patients in discharged group, the patients in un-discharged/died group suffered from decreased counts of total T lymphocytes, CD4 + T lymphocytes, CD8 + T lymphocytes, as well as NK cells at 2 weeks after treatment. Clinical classification-critically severe was the independently risk factor for lymphopenia (OR = 7.701, 95%CI:1.265-46.893, P = 0.027), eosinopenia (OR = 5.595, 95%CI:1.008-31.054, P = 0.049), and worse one-month outcome (OR = 8.984; 95%CI:1.021-79.061, P = 0.048). CONCLUSION: Lymphopenia and eosinopenia may serve as predictors of disease severity and disease progression in COVID-19 patients, and enhancing the cellular immunity may contribute to COVID-19 treatment. Thus, PBICs might become a sentinel of COVID-19, and it deserves attention during COVID-19 treatment.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Eosinófilos/patologia , Subpopulações de Linfócitos/patologia , Linfopenia/diagnóstico , Pneumonia Viral/diagnóstico , Idoso , Biomarcadores/sangue , Contagem de Células , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Progressão da Doença , Eosinófilos/virologia , Feminino , Humanos , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Subpopulações de Linfócitos/virologia , Linfopenia/sangue , Linfopenia/fisiopatologia , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Monócitos/virologia , Neutrófilos/patologia , Neutrófilos/virologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida
7.
Ann Allergy Asthma Immunol ; 125(2): 182-189, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32371242

RESUMO

BACKGROUND: Blood eosinophil counts correlate with exacerbations, but there is a lack of consensus on a clinically relevant definition of eosinophil count elevation. OBJECTIVE: To analyze health care resource use among patients with elevated blood eosinophil counts defined at 150 cells/µL or greater and 300 cells/µL or greater. METHODS: Data on patients who received a diagnosis of asthma between 2007 and 2016 were extracted from EMRClaims + database. Patients were defined as having elevated eosinophil counts if any test result during 3 months before follow-up found blood eosinophil count of 150 cells/µL or more or 300 cells/µL or more. Hospitalizations, emergency department visits, outpatient visits, and associated costs were compared. With logistic regression, likelihood of hospitalization was assessed in the presence of eosinophil elevation. RESULTS: Among 3687 patients who met the study criteria, 1152 received a test within 3 months before the follow-up period, of whom 644 (56%) had elevated eosinophil counts of 150 cells/µL or greater and 322 (29%) had eosinophil counts of 300 cells/µL or greater. Overall, the mean (SD) number of hospitalizations for patients with elevated eosinophil counts vs the comparator was significantly greater (0.29 [0.92] vs 0.17 [0.57], P < .001 at ≥150 cells/µL and 0.30 [0.95] vs 0.18 [0.61] at ≥300 cells/µL, P = .001). The total mean cost was significantly greater for patients with elevated eosinophil counts (at ≥150 cells/µL: $10,262 vs $7149, P < .001 and at ≥300 cells/µL: $9966 vs $7468, P = .003). CONCLUSION: Patients with asthma incurred greater health care resource use when their blood eosinophil counts were elevated at 150 cells/µL or greater and 300 cells/µL or greater as measured within 3 months of follow-up.


Assuntos
Asma/epidemiologia , Eosinófilos/patologia , Hospitalização/estatística & dados numéricos , Contagem de Leucócitos/normas , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/diagnóstico , Feminino , Seguimentos , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
8.
Ann Allergy Asthma Immunol ; 125(2): 177-181, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32371244

RESUMO

BACKGROUND: Asthma is characterized by chronic airway inflammation, and inhaled corticosteroids (ICSs) have been recommended as first-line treatment. However, response to ICS treatment is various, and the prediction of response to ICSs is still difficult, especially in individuals with newly diagnosed asthma. OBJECTIVE: To assess the clinical factors and biomarkers associated with response to ICSs in newly diagnosed asthma. METHODS: A total of 150 ICS-naive patients with newly diagnosed asthma in the allergy clinic of a single tertiary hospital in Korea from January 2014 to January 2019 were included in this study. All patients initially received moderate-dose ICSs and were treated for more than 1 year. We compared the clinical characteristics and parameters between patients with and without acute exacerbation (AE) during the study period. RESULTS: In this study, 99 patients had no AE (stable asthma group), and 51 patients presented with more than 1 AE (unstable asthma group). The mean (SD) blood eosinophil count (635.7 [780.3] × 103/µL vs 373.4 [266.8] × 103/µL, P = .003) and sputum eosinophil count (15.2% [23.9%] vs 8.3% [15.4%], P = .051) were higher and the sputum neutrophil count (42.9% [35.1%] vs 61.3% [35.1%], P = .057) was lower in the stable asthma group than in the unstable asthma group. CONCLUSION: High blood and sputum eosinophil counts can predict a good response to ICS treatment in terms of prevention of AE in individuals with newly diagnosed asthma. The sputum neutrophil count may be an effective predictor of response to ICSs, even though additional studies must be conducted.


Assuntos
Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , Eosinófilos/patologia , Neutrófilos/patologia , Escarro/imunologia , Administração por Inalação , Idoso , Progressão da Doença , Feminino , Humanos , Coreia (Geográfico) , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico
9.
Ann Allergy Asthma Immunol ; 125(3): 304-310.e1, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32387168

RESUMO

BACKGROUND: Predicting postoperative olfactory decline in patients with chronic rhinosinusitis (CRS) remains a considerable challenge. OBJECTIVE: To evaluate patterns of postoperative olfactory function in patients with CRS and explore potential predictors of postoperative olfactory decline. METHODS: A total of 76 patients with CRS electing endoscopic sinus surgery (ESS) were enrolled in this prospective study. Olfaction was assessed with Sniffin' Sticks preoperatively and 3 months postoperatively. Preoperative peripheral venous blood and superior turbinate at surgery were collected for eosinophil quantification. Olfactory cleft was evaluated by computed tomography and endoscopy. Postoperative olfactory decline was defined by a decrease in threshold-discrimination-identification (TDI) score more than 0 point. Multivariable logistic regression analysis was conducted to identify potential predictors associated with postoperative olfactory decline in TDI score. RESULTS: A total of 30.26% of patients with CRS (23/76) presented with olfactory decline 3 months post-ESS. Patients with CRS with olfactory decline showed significantly higher preoperative tissue eosinophils (P < .001), blood eosinophil count (P = .002), blood eosinophil percentage (P = .009), and preoperative TDI scores (P = .017) than patients with CRS without olfactory decline. After adjusting for patient demographics and comorbidities, the preoperative tissue eosinophilia was significantly associated with patients with CRS with postoperative olfactory decline (odds ratio = 1.103; P = .038). An absolute count of 23.5 eosinophils per high-power field in superior turbinate was the best predictor of olfactory decline with the highest area under the receiver operating characteristic curve of 0.901. CONCLUSION: Superior turbinate eosinophilia is highly associated with olfactory decline in patients with CRS 3 months after ESS.


Assuntos
Eosinofilia/etiologia , Transtornos do Olfato/etiologia , Complicações Cognitivas Pós-Operatórias/etiologia , Rinite/etiologia , Sinusite/complicações , Conchas Nasais/patologia , Doença Crônica , Endoscopia/métodos , Eosinofilia/patologia , Eosinófilos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/patologia , Transtornos do Olfato/patologia , Complicações Cognitivas Pós-Operatórias/patologia , Período Pré-Operatório , Rinite/patologia , Sinusite/patologia , Sinusite/cirurgia , Olfato/fisiologia
10.
Scand J Clin Lab Invest ; 80(6): 441-447, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32449374

RESUMO

The Coronavirus Disease (COVID-19) pandemic first broke out in December 2019 in Wuhan, China, and has now spread worldwide. Laboratory findings have been only partially described in some observational studies. To date, more comprehensive systematic reviews of laboratory findings on COVID-19 are missing. We performed a systematic review with a meta-analysis to assess laboratory findings in patients with COVID-19. Observational studies from three databases were selected. We calculated pooled proportions and 95% confidence interval (95% CI) using the random-effects model meta-analysis. A total of 1106 articles were identified from PubMed, Web of Science, CNKI (China), and other sources. After screening, 28 and 7 studies were selected for a systematic review and a meta-analysis, respectively. Of the 4,663 patients included, the most prevalent laboratory finding was increased C-reactive protein (CRP; 73.6%, 95% CI 65.0-81.3%), followed by decreased albumin (62.9%, 95% CI 28.3-91.2%), increased erythrocyte sedimentation rate (61.2%, 95% CI 41.3-81.0%), decreased eosinophils (58.4%, 95% CI 46.5-69.8%), increased interleukin-6 (53.1%, 95% CI 36.0-70.0%), lymphopenia (47.9%, 95% CI 41.6-54.9%), and increased lactate dehydrogenase (LDH; 46.2%, 95% CI 37.9-54.7%). A meta-analysis of seven studies with 1905 patients showed that increased CRP (OR 3.0, 95% CI: 2.1-4.4), lymphopenia (OR 4.5, 95% CI: 3.3-6.0), and increased LDH (OR 6.7, 95% CI: 2.4-18.9) were significantly associated with severity. These results demonstrated that more attention is warranted when interpreting laboratory findings in patients with COVID-19. Patients with elevated CRP levels, lymphopenia, or elevated LDH require proper management and, if necessary, transfer to the intensive care unit.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Linfopenia/diagnóstico , Linfopenia/epidemiologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Adulto , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Eosinófilos/patologia , Eosinófilos/virologia , Feminino , Humanos , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Linfopenia/sangue , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Pneumonia Viral/sangue , Pneumonia Viral/virologia , Albumina Sérica/metabolismo , Índice de Gravidade de Doença
11.
Ann Allergy Asthma Immunol ; 125(2): 171-176, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32334141

RESUMO

BACKGROUND: Blood eosinophil count (BEC) measurements are a noninvasive, relatively reliable surrogate marker for eosinophilic airway inflammation. Single measurements of peripheral BEC greater than or equal to 150 cells/µL predict the response to anti-eosinophil therapies for patients with characteristics of severe eosinophilic asthma. OBJECTIVE: To describe how BECs shift over time for patients with severe, uncontrolled asthma receiving placebo in 2 large, randomized, placebo-controlled clinical trials of benralizumab (SIROCCO and CALIMA). METHODS: Our analysis included all adult patients who were randomized to placebo in the SIROCCO and CALIMA phase III benralizumab studies. Patients were categorized into baseline BEC groups of less than 150 cells/µL, greater than or equal to 150 cells/µL but less than 300 cells/µL, and greater than or equal to 300 cells/µL. The timing of the initial shift from baseline to a different group was evaluated at weeks 4, 8, 24, and 40 and at the end of treatment. Baseline characteristics, including oral corticosteroid use, were described based on the presence or absence of a BEC group shift. RESULTS: Of the 734 evaluable patients, 65% (n = 474) shifted BEC groups during the study, and most patients (86% [n = 410]) shifted by week 24. Patients who started in the less than 150 cells/µL group tended to shift groups earlier, with 59% shifting by week 4 compared with 38% to 55% for other groups in the same time frame. Patients who shifted BEC groups vs those who did not tend to have lower BECs, more oral corticosteroid use, and less incidence of nasal polyps or past polypectomy. CONCLUSION: A single BEC measurement, particularly when low, may be inadequate to help establish a phenotype of severe eosinophilic asthma. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers NCT01928771 (SIROCCO trial) and NCT01914757 (CALIMA trial).


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/diagnóstico , Eosinófilos/patologia , Administração Oral , Adolescente , Adulto , Idoso , Asma/tratamento farmacológico , Criança , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Contagem de Leucócitos/métodos , Masculino , Pessoa de Meia-Idade , Fenótipo , Efeito Placebo , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
12.
Thorax ; 75(7): 600-605, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32303624

RESUMO

Eosinophils are key effector cells in allergic diseases. Here we investigated Mcl-1 (an anti-apoptotic protein) in experimental allergic airway inflammation using transgenic overexpressing human Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Overexpression of Mcl-1 exacerbated allergic airway inflammation, with increased bronchoalveolar lavage fluid cellularity, eosinophil numbers and total protein, and an increase in airway mucus production. Eosinophil apoptosis was suppressed by Mcl-1 overexpression, with this resistance to apoptosis attenuated by cyclin-dependent kinase inhibition which also rescued Mcl-1-exacerbated allergic airway inflammation. We propose that targeting Mcl-1 may be beneficial in treatment of allergic airway disease.


Assuntos
Asma/genética , Eosinófilos/patologia , Regulação da Expressão Gênica , Hipersensibilidade/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , RNA/genética , Animais , Apoptose , Asma/metabolismo , Asma/patologia , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Eosinófilos/metabolismo , Feminino , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia , Contagem de Leucócitos , Camundongos , Camundongos Transgênicos , Proteína de Sequência 1 de Leucemia de Células Mieloides/biossíntese
13.
Am J Surg Pathol ; 44(8): 1137-1142, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32271192

RESUMO

Intestinal inertia is a severe form of gut dysmotility that may require surgical resection. Loss of myenteric ganglion cells has been proposed as a possible etiology. Preclinical models have also suggested that virus infection-associated ganglionitis may be an alternative pathogenic factor. We determined to the extent intestinal inertia is associated with the lack of myenteric ganglion cells or ganglionitis using resection specimens from 27 intestinal inertia and 28 colon cancer patients. A hot spot approach with 5 HPFs was used for quantifying inflammatory cells. CD3, CD8, and CD20 immunohistochemistry was used to quantify T and B lymphocytes, along with subtyping the T-lymphocyte population by CD8. None of the intestinal inertia nor control cases showed the absence of myenteric ganglion cells. A total of 15 (55.6%) of the intestinal inertia cases showed inflammatory cell infiltration in the myenteric ganglion cells, compared with only 1 of 28 (3.6%) control cases (P<0.0001 by Fisher exact test). The inertia cases with inflammatory infiltrates were all associated predominantly with lymphocytes, including 3 cases (11.1%) with concurrent eosinophil infiltration, and 1 case (3.7%) with concurrent neutrophil infiltration. Furthermore, all 15 inertia cases with myenteric lymphocytic ganglionitis were associated with T lymphocytes (100%), including 1 case with a subset of concurrent B lymphocytes. The average CD3 count was 3.8 cells/HPF. CD8 immunohistochemical stain showed positive staining in 12 of the 15 cases (80%) with CD8-positive cells ranging from 1 to 8/HPF. In contrast, the only control case with lymphocytic ganglionitis showed mixed B and T lymphocytes and eosinophils. The high prevalence of T-lymphocyte infiltration in the myenteric ganglion in intestinal inertia cases suggests a possible pathogenic role.


Assuntos
Linfócitos T CD8-Positivos/patologia , Constipação Intestinal/patologia , Defecação , Gânglios Autônomos/patologia , Motilidade Gastrointestinal , Intestinos/inervação , Plexo Mientérico/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Linfócitos B/patologia , Linfócitos T CD8-Positivos/imunologia , Doença Crônica , Constipação Intestinal/imunologia , Constipação Intestinal/fisiopatologia , Constipação Intestinal/cirurgia , Eosinófilos/imunologia , Eosinófilos/patologia , Feminino , Gânglios Autônomos/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Plexo Mientérico/imunologia , Infiltração de Neutrófilos , Estudos Retrospectivos
15.
Trop Doct ; 50(3): 277-279, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32178592

RESUMO

Eosinophilic ascites, owing to serosal involvement, is a very rare manifestation of eosinophilic gastroenteritis in children, especially when it occurs with muscular involvement in the absence of mucosal disease, which may be confirmed by endoscopic ultrasonography. An 11-year-old girl, presenting with massive eosinophilic ascites and colicky abdominal pain with peripheral eosinophilia, raised IgE levels and positive skin prick test, had such investigation which confirmed the presence of muscle layer thickening of both stomach and small bowel. She responded well to steroids and montelukast.


Assuntos
Ascite/diagnóstico , Enterite/diagnóstico , Eosinofilia/diagnóstico , Gastrite/diagnóstico , Músculos Abdominais/diagnóstico por imagem , Músculos Abdominais/patologia , Ascite/tratamento farmacológico , Ascite/patologia , Criança , Endossonografia , Enterite/tratamento farmacológico , Enterite/patologia , Eosinofilia/tratamento farmacológico , Eosinofilia/patologia , Eosinófilos/patologia , Feminino , Gastrite/tratamento farmacológico , Gastrite/patologia , Humanos , Esteroides/uso terapêutico , Resultado do Tratamento
17.
Am J Surg ; 219(4): 592-597, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32209240

RESUMO

BACKGROUND: The aim of this study was to determine whether acute histologic inflammatory activity at the rectal margin predicts postoperative complications in children with ulcerative colitis following ileal pouch-anal anastomoses (IPAA). METHODS: Patients who underwent IPAA following previous total abdominal colectomy for ulcerative colitis between 2006 and 2014 were included. Data collected included demographics, operative and postoperative data, histologic grading of the rectal margin at time of IPAA, and stooling outcomes at one, six and 12 months following ileostomy closure. RESULTS: Twenty-seven patients were included. Acute inflammation scores ranged between 2 and 13. Unadjusted and adjusted models showed no statistically significant relationship between inflammation and presence of any postoperative complications, number of daily stools, nighttime stooling, soiling, or stool-altering medication usage. CONCLUSION: Acute histologic inflammatory activity at the rectal margin is not associated with increased rates of postoperative complications following IPAA creation in children, nor with poorer continence outcomes following ileostomy closure.


Assuntos
Colite Ulcerativa/patologia , Colite Ulcerativa/cirurgia , Mucosa Intestinal/patologia , Reto/patologia , Adolescente , Estudos de Coortes , Bolsas Cólicas , Eosinófilos/patologia , Incontinência Fecal/etiologia , Feminino , Humanos , Fístula Intestinal/etiologia , Mucosa Intestinal/cirurgia , Obstrução Intestinal/etiologia , Leucócitos Mononucleares/patologia , Masculino , Neutrófilos/patologia , Complicações Pós-Operatórias , Pouchite/etiologia , Proctocolectomia Restauradora , Reto/cirurgia , Estudos Retrospectivos
20.
Am J Respir Cell Mol Biol ; 63(1): 25-35, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32101465

RESUMO

Diisocyanates are well-recognized causes of asthma. However, sensitized workers frequently lack diisocyanate-specific IgE, which complicates diagnosis and suggests the disease involves IgE-independent mechanisms. We used a mouse model of methylene diphenyl diisocyanate (MDI) asthma to identify biological pathways that may contribute to asthma pathogenesis. MDI sensitization and respiratory tract exposure were performed in Balb/c, transgenic B-cell (e.g., IgE)-deficient mice and a genetic background (C57BL/6)-matched strain. Eosinophils in airway fluid were quantitated by flow cytometry. Lung tissue gene expression was assessed using whole-genome mRNA microarrays. Informatic software was used to identify biological pathways affected by respiratory tract exposure and potential targets for disease intervention. Airway eosinophilia and changes (>1.5-fold; P value < 0.05) in expression of 192 genes occurred in all three mouse strains tested, with enrichment in chemokines and a pattern associated with alternatively activated monocytes/macrophages. CLCA1 (calcium-activated chloride channel regulator 1) was the most upregulated gene transcript (>100-fold) in all exposed mouse lungs versus controls, followed closely by SLC26A4, another transcript involved in Cl- conductance. Crofelemer, a U.S. Food and Drug Administration-approved Cl- channel inhibitor, reduced MDI exposure induction of airway eosinophilia, mucus, CLCA1, and other asthma-associated gene transcripts. Expression changes in a core set of genes occurs independent of IgE in a mouse model of chemical-induced airway eosinophilia. In addition to chemokines and alternatively activated monocytes/macrophages, the data suggest a crucial role for Cl- channels in diisocyanate asthma pathology and as a possible target for intervention.


Assuntos
Asma/metabolismo , Asma/patologia , Canais de Cloreto/metabolismo , Eosinofilia/metabolismo , Eosinófilos/metabolismo , Expressão Gênica/fisiologia , Pulmão/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Eosinofilia/induzido quimicamente , Eosinófilos/patologia , Expressão Gênica/efeitos dos fármacos , Imunoglobulina E/metabolismo , Isocianatos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Monócitos/efeitos dos fármacos , Monócitos/metabolismo
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