RESUMO
Dental care workers are frequently exposed to various types of volatile organic and inorganic compounds. In addition to biological materials, these compounds include silica, heavy metals, and acrylic plastics. Such exposures may cause respiratory symptoms, but the nonspecific nature of these symptoms often means that the etiology is difficult to discern. The disease severity depends on the particle size and type of the inhaled compounds, as well as the duration and intensity of exposure, which varies markedly among dental workers. Here, we present two unique cases with the same occupational exposure. Both patients showed radiological changes in the lungs that were suspicious for lung cancer. The first patient did not undergo a biopsy due to cardiac comorbidities and risk of bleeding, and the diagnosis was based on thoracic computer tomography (CT) which confirmed multiple, bilateral, solid, smooth, partly calcified lung nodules, normal positron emission tomography (PET)-CT and the relevant occupational exposure. In the second case, a CT-guided biopsy and thoracoscopic resection was done with histopathological findings consistent with granuloma. The multi-disciplinary team decision of both cases was consistent with occupational exposure related lunge disease. This is the first case study report whereby same occupational exposure related health condition is compared with two different approaches. Respiratory clinicians should be aware of this potential diagnosis, especially for asymptomatic patients with relevant exposures. Careful attention to the occupational history may help to prevent unnecessary, invasive diagnostic procedures or surgeries.
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Chronic inflammation such as asthma may lead to higher risks of malignancy, which may be inhibited by anti-inflammatory medicine such as inhaled corticosteroids (ICS). The aim of this study was to evaluate if patients with asthma-Chronic Obstructive Pulmonary Disease (COPD) overlap have a higher risk of malignancy than patients with COPD without asthma, and, secondarily, if inhaled corticosteroids modify such a risk in a nationwide multi-center retrospective cohort study of Danish COPD-outpatients with or without asthma. Patients with asthma-COPD overlap were propensity score matched (PSM) 1:2 to patients with COPD without asthma. The endpoint was cancer diagnosis within 2 years. Patients were stratified depending on prior malignancy within 5 years. ICS was explored as a possible risk modifier. We included 50,897 outpatients with COPD; 88% without prior malignancy and 20% with asthma. In the PSM cohorts, 26,003 patients without prior malignancy and 3331 patients with prior malignancy were analyzed. There was no association between asthma-COPD overlap and cancer with hazard ratio (HR) = 0.92, CI = 0.78-1.08, p = 0.31 (no prior malignancy) and HR = 1.04, CI = 0.85-1.26, and p = 0.74 (prior malignancy) as compared to patients with COPD without asthma. ICS did not seem to modify the risk of cancer. In conclusion, in our study, asthma-COPD overlap was not associated with an increased risk of cancer events.
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Aspergillomas are found in pre-existing cavities in pulmonary parenchyma. To the best of our knowledge, aspergilloma has not previously been reported in COVID-19-associated pulmonary architecture distortion combined with barotrauma from invasive mechanical ventilation therapy. We present a case of a 67-year-old woman, who suffered from severe COVID-19 in the summer of 2020 with no suspicion of infection with Aspergillus in the acute phase. Ten months after discharge from her COVID-related admission, she developed bilateral aspergillomas diagnosed by image diagnostics, bronchoscopy, and blood samples, and she now receives antifungal therapy. We would like to raise awareness on aspergilloma in post-COVID-19 patients, since it is an expected long-term complication to COVID-19 patients with pulmonary architectural distortion.
Assuntos
COVID-19 , Pneumonia , Aspergilose Pulmonar , Idoso , Broncoscopia , COVID-19/complicações , Feminino , Humanos , Pulmão/diagnóstico por imagem , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/diagnósticoRESUMO
We describe characteristics and risk factors regarding pregnancy outcome in women with a preconception body mass index (BMI) >50 kg/m² compared with women with BMI ≤50 kg/m² in a retrospective population cohort study in singleton pregnancies from the Danish Medical Birth Registry. Results were analyzed as relative risks by a two-proportion z-test. Women with preconception BMI >50 kg/m² smoked, developed gestational diabetes and pre-eclampsia, and needed induction of labor more frequently than mothers with BMI ≤50 kg/m². Examination of the case records showed that many attempted vaginal delivery without epidural analgesia, 21% needed an emergency cesarean section (compared with 12% among women with BMI ≤50 kg/m²), and 25% underwent general anesthesia in this context. Many neonates were macrosomic and 34% needed neonatal intensive care and early feeding compared with 6% of neonates from women with BMI ≤50 kg/m². Women with an extremely high preconception BMI develop more pregnancy complications and their neonates appear affected by this as well.
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Diabetes Gestacional/diagnóstico , Obesidade/complicações , Pré-Eclâmpsia/diagnóstico , Resultado da Gravidez/epidemiologia , Fumar/efeitos adversos , Adulto , Índice de Massa Corporal , Cesárea , Estudos de Coortes , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/etiologia , Feminino , Humanos , Incidência , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/etiologia , Gravidez , Sistema de Registros , Fatores de RiscoRESUMO
BACKGROUND: The majority of patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced inoperable disease. While treatment with conventional chemotherapy has improved during the last decade the 5 years survival is still modest. Novel drugs, which selectively target aberrant elements in neoplastic cells and their microenvironment have recently been and are continuously developed including drugs inhibiting the angiogenic system. Angiogenic factor vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) seem to play key roles in tumour-induced angiogenesis. Previous studies have been inconclusive on the topic of a role for VEGF and its receptor as prognostic factors in NSCLC. METHODS: Paraffin-embedded histological material from 102 patients operated for NSCLC was included and a representative block with lung cancer tissue was selected from each patient for immunohistochemical studies. The sections were incubated with primary monoclonal antibodies to VEGF-A and VEGFR2. The expression of the immunohistochemical staining was assessed semi-quantitatively by estimating the percentage and the intensity of tumour cells stained on whole tumour slides. Kaplan-Meier survival curves were generated to evaluate the significance of immunohistochemical VEGF-A and VEGFR2 expression for the prognosis. RESULTS: VEGF-A and VEGFR2 expression was observed in the majority of NSCLC patients. VEGF-A expression showed a correlation to histological type with increased expression in adenocarcinomas as compared to squamous cell carcinomas. There was no statistically significant correlation between VEGF-A and VEGFR2 expression and age, gender or stage at diagnosis. Finally there was no relation between expression of VEGF-A and VEGFR2, nor an effect of high expression of both VEGF-A and VEGFR2 on survival. CONCLUSION: In conclusion VEGF-A and VEGFR2 are expressed in NSCLC, but the immunohistochemical expression of VEGF-A and VEGFR2 has no prognostic impact in NSCLC. We show that the histological subgroups of NSCLC express VEGF-A differently, with adenocarcinomas having the highest amount. Whether these markers might be useful as clinically reliable predictive markers remains to be solved.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Prognóstico , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
MEK kinase 1 (MEKK1) is a potent JNK-activating kinase, a regulator of T helper cell differentiation, cytokine production and proliferation in vitro. Using mice deficient for MEKK1 activity (Mekk1(DeltaKD)) exclusively in their hematopoietic system, we show that MEKK1 has a negative regulatory role in the generation of a virus-specific immune response. Mekk1(DeltaKD) mice challenged with vesicular stomatitis virus (VSV) showed a fourfold increase in splenic CD8(+) T cell numbers. In contrast, the number of splenic T cells in infected WT mice was only marginally increased. The CD8(+) T cell expansion in Mekk1(DeltaKD) mice following VSV infection is virus-specific and the frequency of virus-specific T cells is significantly higher (more than threefold) in Mekk1(DeltaKD) as compared to WT animals. Moreover, the hyper-expansion of T cells seen in Mekk1(DeltaKD) mice after VSV infection is a result of increased proliferation, since a significantly higher percentage of virus-specific Mekk1(DeltaKD) CD8(+) T cells incorporated BrdU as compared to virus-specific WT CD8(+) T cells. In contrast, similar levels of apoptosis were detected in Mekk1(DeltaKD) and WT T cells following VSV infection. These results strongly suggest that MEKK1 plays a negative regulatory role in the expansion of virus-specific CD8(+) T cells in vivo.
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Linfócitos T CD8-Positivos/enzimologia , Linfócitos T CD8-Positivos/imunologia , MAP Quinase Quinase Quinase 1/metabolismo , Infecções por Rhabdoviridae/enzimologia , Infecções por Rhabdoviridae/imunologia , Vírus da Estomatite Vesicular Indiana/imunologia , Animais , Células Apresentadoras de Antígenos/enzimologia , Células Apresentadoras de Antígenos/imunologia , Linfócitos T CD8-Positivos/citologia , Linhagem Celular , Proliferação de Células , Quimera , Técnicas de Cultura Embrionária , Feminino , Amplificação de Genes/genética , Imunidade Inata/imunologia , Fígado/enzimologia , Fígado/imunologia , MAP Quinase Quinase Quinase 1/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Infecções por Rhabdoviridae/patologia , Infecções por Rhabdoviridae/virologiaRESUMO
Mitogen-activated protein kinase/extracellular signal to regulated kinase (MEK) kinase 1 (MEKK1) is a c-Jun N-terminal kinase (JNK) activating kinase known to be implicated in proinflammatory responses and cell motility. Using mice deficient for MEKK1 kinase activity (Mekk1(DeltaKD)) we show a role for MEKK1 in definitive mouse erythropoiesis. Although Mekk1(DeltaKD) mice are alive and fertile on a 129 x C57/BL6 background, the frequency of Mekk1(DeltaKD) embryos that develop past embryonic day (E) 14.5 is dramatically reduced when backcrossed into the C57/BL6 background. At E13.5, Mekk1(DeltaKD) embryos have normal morphology but are anemic due to failure of definitive erythropoiesis. When Mekk1(DeltaKD) fetal liver cells were transferred to lethally irradiated wild-type hosts, mature red blood cells were generated from the mutant cells, suggesting that MEKK1 functions in a non-cell-autonomous manner. Based on immunohistochemical and hemoglobin chain transcription analysis, we propose that the failure of definitive erythropoiesis is due to a deficiency in enucleation activity caused by insufficient macrophage-mediated nuclear DNA destruction.