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1.
Front Immunol ; 11: 1312, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582222

RESUMO

Respiratory, circulatory, and renal failure are among the gravest features of COVID-19 and are associated with a very high mortality rate. A common denominator of all affected organs is the expression of angiotensin-converting enzyme 2 (ACE2), a protease responsible for the conversion of Angiotensin 1-8 (Ang II) to Angiotensin 1-7 (Ang 1-7). Ang 1-7 acts on these tissues and in other target organs via Mas receptor (MasR), where it exerts beneficial effects, including vasodilation and suppression of inflammation and fibrosis, along an attenuation of cardiac and vascular remodeling. Unfortunately, ACE2 also serves as the binding receptor of SARS viral spike glycoprotein, enabling its attachment to host cells, with subsequent viral internalization and replication. Although numerous reports have linked the devastating organ injuries to viral homing and attachment to organ-specific cells widely expressing ACE2, little attention has been given to ACE-2 expressed by the immune system. Herein we outline potential adverse effects of SARS-CoV2 on macrophages and dendritic cells, key cells of the immune system expressing ACE2. Specifically, we propose a new hypothesis that, while macrophages play an important role in antiviral defense mechanisms, in the case of SARS-CoV, they may also serve as a Trojan horse, enabling viral anchoring specifically within the pulmonary parenchyma. It is tempting to assume that diverse expression of ACE2 in macrophages among individuals might govern the severity of SARS-CoV-2 infection. Moreover, reallocation of viral-containing macrophages migrating out of the lung to other tissues is theoretically plausible in the context of viral spread with the involvement of other organs.


Assuntos
Betacoronavirus/metabolismo , Células Dendríticas/metabolismo , Pulmão/patologia , Macrófagos Alveolares/metabolismo , Peptidil Dipeptidase A/metabolismo , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , Humanos , Pulmão/virologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/virologia , Pandemias , Tecido Parenquimatoso/patologia , Tecido Parenquimatoso/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Receptores Virais/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo
2.
Nature ; 578(7796): 610-614, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32076265

RESUMO

The sympathetic nervous system innervates peripheral organs to regulate their function and maintain homeostasis, whereas target cells also produce neurotrophic factors to promote sympathetic innervation1,2. The molecular basis of this bi-directional communication remains to be fully determined. Here we use thermogenic adipose tissue from mice as a model system to show that T cells, specifically γδ T cells, have a crucial role in promoting sympathetic innervation, at least in part by driving the expression of TGFß1 in parenchymal cells via the IL-17 receptor C (IL-17RC). Ablation of IL-17RC specifically in adipose tissue reduces expression of TGFß1 in adipocytes, impairs local sympathetic innervation and causes obesity and other metabolic phenotypes that are consistent with defective thermogenesis; innervation can be fully rescued by restoring TGFß1 expression. Ablating γδ Τ cells and the IL-17RC signalling pathway also impairs sympathetic innervation in other tissues such as salivary glands. These findings demonstrate coordination between T cells and parenchymal cells to regulate sympathetic innervation.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/inervação , Tecido Adiposo/metabolismo , Interleucina-17/metabolismo , Sistema Nervoso Simpático/fisiologia , Linfócitos T/metabolismo , Termogênese , Tecido Adiposo Marrom/metabolismo , Animais , Interleucina-17/deficiência , Interleucina-17/genética , Masculino , Camundongos , Camundongos Knockout , Especificidade de Órgãos , Tecido Parenquimatoso/citologia , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
3.
Eur Radiol ; 30(1): 195-205, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31392481

RESUMO

OBJECTIVES: This study aims to measure the reproducibility of radiomic features in pancreatic parenchyma and ductal adenocarcinomas (PDAC) in patients who underwent consecutive contrast-enhanced computed tomography (CECT) scans. METHODS: In this IRB-approved and HIPAA-compliant retrospective study, 37 pairs of scans from 37 unique patients who underwent CECTs within a 2-week interval were included in the analysis of the reproducibility of features derived from pancreatic parenchyma, and a subset of 18 pairs of scans were further analyzed for the reproducibility of features derived from PDAC. In each patient, pancreatic parenchyma and pancreatic tumor (when present) were manually segmented by two radiologists independently. A total of 266 radiomic features were extracted from the pancreatic parenchyma and tumor region and also the volume and diameter of the tumor. The concordance correlation coefficient (CCC) was calculated to assess feature reproducibility for each patient in three scenarios: (1) different radiologists, same CECT; (2) same radiologist, different CECTs; and (3) different radiologists, different CECTs. RESULTS: Among pancreatic parenchyma-derived features, using a threshold of CCC > 0.90, 58/266 (21.8%) and 48/266 (18.1%) features met the threshold for scenario 1, 14/266 (5.3%) and 15/266 (5.6%) for scenario 2, and 14/266 (5.3%) and 10/266 (3.8%) for scenario 3. Among pancreatic tumor-derived features, 11/268 (4.1%) and 17/268 (6.3%) features met the threshold for scenario 1, 1/268 (0.4%) and 5/268 (1.9%) features met the threshold for scenario 2, and no features for scenario 3 met the threshold, respectively. CONCLUSIONS: Variations between CECT scans affected radiomic feature reproducibility to a greater extent than variation in segmentation. A smaller number of pancreatic tumor-derived radiomic features were reproducible compared with pancreatic parenchyma-derived radiomic features under the same conditions. KEY POINTS: • For pancreatic-derived radiomic features from contrast-enhanced CT (CECT), fewer than 25% are reproducible (with a threshold of CCC < 0.9) in a clinical heterogeneous dataset. • Variations between CECT scans affected the number of reproducible radiomic features to a greater extent than variations in radiologist segmentation. • A smaller number of pancreatic tumor-derived radiomic features were reproducible compared with pancreatic parenchyma-derived radiomic features under the same conditions.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Algoritmos , Meios de Contraste/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tecido Parenquimatoso/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos
4.
Int J Mol Sci ; 21(1)2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878253

RESUMO

The xylem is a complex system that includes a network of dead conduits ensuring long-distance water transport in plants. Under ongoing climate changes, xylem embolism is a major and recurrent cause of drought-induced tree mortality. Non-structural carbohydrates (NSC) play key roles in plant responses to drought and frost stress, and several studies putatively suggest their involvement in the regulation of xylem water transport. However, a clear picture on the roles of NSCs in plant hydraulics has not been drawn to date. We summarize the current knowledge on the involvement of NSCs during embolism formation and subsequent hydraulic recovery. Under drought, sugars are generally accumulated in xylem parenchyma and in xylem sap. At drought-relief, xylem functionality is putatively restored in an osmotically driven process involving wood parenchyma, xylem sap and phloem compartments. By analyzing the published data on stem hydraulics and NSC contents under drought/frost stress and subsequent stress relief, we found that embolism build-up positively correlated to stem NSC depletion, and that the magnitude of post-stress hydraulic recovery positively correlated to consumption of soluble sugars. These findings suggest a close relationship between hydraulics and carbohydrate dynamics. We call for more experiments on hydraulic and NSC dynamics in controlled and field conditions.


Assuntos
Amido/metabolismo , Xilema/metabolismo , Carboidratos/fisiologia , Secas , Tecido Parenquimatoso/metabolismo , Árvores/metabolismo , Árvores/fisiologia
5.
Respir Res ; 20(1): 284, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842871

RESUMO

BACKGROUND: Recent advances in the functional analyses of endogenous non-coding RNA (ncRNA) molecules, including long non-coding RNAs (LncRNAs), have provided a new perspective on the crucial roles of RNA in gene regulation. Consequently, LncRNA deregulation is a key factor in various diseases, including pulmonary disorders like Cystic Fibrosis (CF). CF is the most common life limiting recessive disease in the U.S., and is due to mutations in the CFTR gene. CF mutations, of which the most common is F508del-CFTR, prevents correct folding, trafficking and function of the mutant CFTR protein and is further manifested by the hyper-expression of pro-inflammatory cytokines and chemokines into the airway lumen leading to bronchiectasis and culminating in lung destruction. METHODS: Here we report a distinct LncRNA signature and corresponding mRNAs that distinguishes CF lung (airway and parenchyma) tissues from matched non-CF controls (n = 4 each group), generated by microarray specific for LncRNAs which includes corresponding mRNA expressions. In silico analyses of the cellular processes that are impacted by these LncRNAs was performed using Gene Ontology (GO). A selected subset of LncRNAs were validated by quantitative real-time PCR. RESULTS: We have identified 636 LncRNAs differentially expressed in CF airway epithelium and 1974 in CF lung parenchyma compared to matched non-CF controls (fold change ≥2, p < 0.05), majority of which (> 50%) are intergenic. Interestingly, 15 of these differentially expressed LncRNAs and 9 coding mRNAs are common to airway and parenchyma tissues. GO analyses indicates that signaling pathways and cell membrane functions are significantly affected by the alteration in LncRNA expressions in CF lung tissues. Seven of the differentially expressed LncRNAs, exhibit similar expression trends in CFBE41o- compared to control cells. CONCLUSION: Understanding the mechanisms by which these LncRNAs regulate CF disease phenotype will help develop novel therapeutic targets for CF and related pulmonary diseases, such as COPD and Asthma.


Assuntos
Fibrose Cística/genética , Células Epiteliais/metabolismo , Perfilação da Expressão Gênica , Pulmão/metabolismo , Tecido Parenquimatoso/metabolismo , RNA Longo não Codificante/genética , Transcriptoma , Adolescente , Adulto , Estudos de Casos e Controles , Linhagem Celular , Fibrose Cística/diagnóstico , Fibrose Cística/metabolismo , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Adulto Jovem
6.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(11): 852-857, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31694096

RESUMO

Objective: To analyze the clinical,imaging and pathological features of Pleuroparenehymal fibroelastosis (PPFE). Methods: The clinieal data of a patient diagnosed as PPFE admitted in department of Respiratory and Critical Care Medicine,Beijing Hospital in April 2017 were reported and the related literatures were reviewed.With "pleuroparenehymal fibroelastosis" as the search terms, and the search time before October 1st 2017 for Wanfangdata, China National Knowledge Infrastructure(CNKI), and PubMed. Results: The patient was a 46-year-old male presented with cough, shortness of breath after exercise.A CT scan of the chest revealed bilateral, irregular pleural thickening with upper lobe predominance.After 3 years of antituberculosis treatment,the disease progressed. A diagnosis of pleuroparenehymal fibroelastosis (PPFE) was confirmed by CT guided lung biopsy. A total of 132 cases were reported (including 1 case in Chinese). 88 of them were confirmed by pathology with detailed data.Clinical data of 89 reported cases with PPFE including 48 males and 41 females aged 13 to 85 years were enrolled and analyzed in the study.The common symptoms were dyspnea(62%, 55 cases),cough(58%, 52 cases),recurrent respiratory tract infection(17%, 15 cases).The main CT features are reported:pleural thickening(87%,77 cases), recurrent pneumothorax(52%,46 cases), traction bronchiectasis(30%, 27 cases),subpleural comsolidation(20%, 18 cases). All patients were proven PPFE by biopsy.34 cases received corticosteroid, 5 cases received lung transplant operation.40 cases died during the follow-up from 4 month to 84 month. Conclusions: Pleuroparenehymal fibroelastosis is a rare disease.The imaging findings were dominated by both upper lobes. Lung biopsy might be necessary. PPFE is often misdiagnosed as pulmonary tuberculosis/obsolete pulmonary tuberculosis,asbestosis,connective tissues disease and Drug-induced pneumonitis.There was no consensus on the treatment.


Assuntos
Pulmão/diagnóstico por imagem , Tecido Parenquimatoso/patologia , Pleura/patologia , Doenças Pleurais/patologia , Fibrose Pulmonar/patologia , Biópsia , China , Tosse/etiologia , Dispneia/etiologia , Feminino , Humanos , Pulmão/patologia , Pulmão/cirurgia , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Tecido Parenquimatoso/diagnóstico por imagem , Pleura/diagnóstico por imagem , Doenças Pleurais/diagnóstico por imagem , Doenças Pleurais/cirurgia , Fibrose Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Ann Surg Oncol ; 26(13): 4576-4586, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31605335

RESUMO

BACKGROUND: Parenchymal-sparing hepatectomy (PSH) is regarded as the standard of care for colorectal liver metastases (CRLMs) in open surgery. However, the surgical and oncological benefits of laparoscopic PSH compared with laparoscopic major hepatectomy (MH) have not been fully documented. METHODS: A total of 269 patients who underwent initial laparoscopic liver resections with curative intent for CRLMs between 2004 and 2017 were enrolled. Preoperative patient characteristics and tumor burden were adjusted with propensity score matching, and laparoscopic PSH was compared with laparoscopic MH after matching. RESULTS: PSH was performed in 148 patients, while MH was performed in 121 patients. After propensity score matching, 82 PSH and 82 MH patients showed similar preoperative characteristics. PSH was associated with lower rates of major postoperative complications compared with MH (6.1 vs. 15.9%; p = 0.046). Recurrence-free survival (RFS) and liver-specific RFS rates were comparable between both groups (p = 0.595 and 0.683). Repeat hepatectomy for liver recurrence was more frequently performed in the PSH group (63.9 vs. 36.4%; p = 0.022), and the PSH group also showed a trend toward a higher overall survival (OS) rate (5-year OS 79.4 vs. 64.3%; p = 0.067). Multivariate analyses revealed that initial MH was one of the risk factors to preclude repeat hepatectomy after liver recurrence (hazard ratio 2.39, p = 0.047). CONCLUSIONS: Laparoscopic PSH provided surgical and oncological benefits for CRLMs, with less complications, similar recurrence rates, and increased salvageability through repeat hepatectomy, compared with laparoscopic MH. PSH should be the standard approach, even in laparoscopic procedures.


Assuntos
Neoplasias Colorretais/mortalidade , Hepatectomia/mortalidade , Laparoscopia/mortalidade , Neoplasias Hepáticas/mortalidade , Tratamentos com Preservação do Órgão/métodos , Tecido Parenquimatoso/cirurgia , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida
8.
Fluids Barriers CNS ; 16(1): 32, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31564250

RESUMO

BACKGROUND: Influx and clearance of substances in the brain parenchyma occur by a combination of diffusion and convection, but the relative importance of these mechanisms is unclear. Accurate modeling of tracer distributions in the brain relies on parameters that are partially unknown and with literature values varying by several orders of magnitude. In this work, we rigorously quantified the variability of tracer distribution in the brain resulting from uncertainty in diffusion and convection model parameters. METHODS: Using the convection-diffusion-reaction equation, we simulated tracer distribution in the brain parenchyma after intrathecal injection. Several models were tested to assess the uncertainty both in type of diffusion and velocity fields and also the importance of their magnitude. Our results were compared with experimental MRI results of tracer enhancement. RESULTS: In models of pure diffusion, the expected amount of tracer in the gray matter reached peak value after 15 h, while the white matter did not reach peak within 24 h with high likelihood. Models of the glymphatic system were similar qualitatively to the models of pure diffusion with respect to expected time to peak but displayed less variability. However, the expected time to peak was reduced to 11 h when an additional directionality was prescribed for the glymphatic circulation. In a model including drainage directly from the brain parenchyma, time to peak occured after 6-8 h for the gray matter. CONCLUSION: Even when uncertainties are taken into account, we find that diffusion alone is not sufficient to explain transport of tracer deep into the white matter as seen in experimental data. A glymphatic velocity field may increase transport if a large-scale directional structure is included in the glymphatic circulation.


Assuntos
Encéfalo/metabolismo , Convecção , Difusão , Sistema Glinfático/metabolismo , Modelos Neurológicos , Tecido Parenquimatoso/metabolismo , Animais , Transporte Biológico , Líquido Cefalorraquidiano/metabolismo , Líquido Extracelular/metabolismo , Substância Cinzenta/metabolismo , Humanos , Substância Branca/metabolismo
9.
Nat Rev Cancer ; 19(11): 605, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31548603
11.
Am J Trop Med Hyg ; 101(4): 812-820, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31452498

RESUMO

Calcified neurocysticercosis (NCC), previously thought to be a dead end, is an important risk factor for seizure recurrences. We studied the pattern of seizure recurrences and associated radiological findings in children with calcified NCC. In this ambispective cohort study, we enrolled children (age 1-15 years) with calcified NCC attending the pediatric NCC clinic between January 2017 and December 2017. Retrospective data were collected from the hospital records, and all enrolled children were prospectively followed up till June 2018. The study group divided into two groups: 1) children first presenting with calcified granuloma and 2) children presented with ring-enhancing lesion (REL) and transformed into the calcified lesion during follow-up imaging. During the study period (January 2017-December 2017), 520 children with NCC were screened and 128 with calcified NCC were enrolled. The mean age was 10.8 ± 3.2 years, and 63% were boys. Among 128 children, 40 (31%) had calcified granuloma and 88 (69%) had REL transformed to calcified granuloma. Sixty-one (49%) children had seizure recurrence: 22 (58%) within calcified granuloma group and 39 (45%) within REL transformed to calcified granuloma group (P = 0.18). Seizure recurrence was associated with the presence of perilesional edema (PE) in 35 (57.4%) children on computed tomography scan. The median interval between two seizure recurrences was 30 (17-56) months, and the median antiepileptic drug-free interval was 17 (12-22) months. The total duration of continued seizures was 42 (26-58) months, slightly longer in children with REL transformed to calcified granuloma group (42, 95% CI: 18-66 months) in comparison to calcified granuloma group (35, 95% CI: 10-60 months, P = 0.32). To conclude, children with calcified NCC have seizure recurrences over a prolonged period. Seizure recurrences are intermittent and may be interspersed with a prolonged period of quiescence in between. The presence of PE and contrast enhancement around the lesion during seizure recurrence suggests lesion reactivation.


Assuntos
Anticonvulsivantes/administração & dosagem , Edema/diagnóstico por imagem , Granuloma/diagnóstico por imagem , Neurocisticercose/diagnóstico por imagem , Convulsões/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Edema/tratamento farmacológico , Feminino , Seguimentos , Granuloma/tratamento farmacológico , Humanos , Índia , Masculino , Neurocisticercose/tratamento farmacológico , Tecido Parenquimatoso/diagnóstico por imagem , Estudos Prospectivos , Radiografia , Recidiva , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Tomografia Computadorizada por Raios X
12.
Vet Radiol Ultrasound ; 60(6): 734-744, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31418983

RESUMO

The aim of this retrospective, cross-sectional, study was to evaluate clinical findings and outcomes for different ultrasonographic patterns of hepatic emphysema in dogs and cats. Dogs and cats with an ultrasonographic diagnosis of hepatic emphysema and a known outcome, from January 2010 to January 2018, were enrolled. The following data were recorded from medical and ultrasonographic records: ultrasonographic patterns of hepatic emphysema (parenchymal, portal venous, biliary), clinical signs, laboratory findings, and outcomes (favorable, poor). A total of 33 dogs and four cats met the inclusion criteria. Among these, 23 cases were classified as hepatic portal venous gas, 10 as parenchymal emphysema, and four as biliary emphysema. Clinical diagnosis categories were as follows: infection/sepsis (9), gastro-intestinal disease (9), iatrogenic (9), trauma (5), and liver neoplasia (5). An increase in serum liver enzymes was significantly associated with parenchymal emphysema (P = .03). Other clinical and laboratory findings were not associated with the type of hepatic emphysema. Hepatic portal venous gas was mostly transient in patients with ultrasonographic follow-up. The overall mortality was 40.5%. A significant difference was found between mortality by portal venous gas (21.7%) and mortality by parenchymal emphysema (90%) (P = .003). In conclusion, the ultrasonographic differentiation of hepatic emphysema between hepatic portal venous gas and parenchymal emphysema may be important for the prognosis of hepatic emphysema. The presence of parenchymal emphysema may be a poor prognostic indicator, while hepatic portal venous gas may be more benign. However, ultrasound findings should be carefully evaluated in the context of clinical findings.


Assuntos
Doenças do Gato/diagnóstico por imagem , Doenças do Cão/diagnóstico por imagem , Enfisema/veterinária , Gases , Hepatopatias/veterinária , Tecido Parenquimatoso/diagnóstico por imagem , Veia Porta/diagnóstico por imagem , Animais , Gatos , Estudos Transversais , Cães , Enfisema/diagnóstico por imagem , Feminino , Hepatopatias/diagnóstico por imagem , Masculino , Prognóstico , Estudos Retrospectivos , Ultrassonografia/veterinária
13.
Nature ; 572(7771): 603-608, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31462798

RESUMO

Direct investigation of the early cellular changes induced by metastatic cells within the surrounding tissue remains a challenge. Here we present a system in which metastatic cancer cells release a cell-penetrating fluorescent protein, which is taken up by neighbouring cells and enables spatial identification of the local metastatic cellular environment. Using this system, tissue cells with low representation in the metastatic niche can be identified and characterized within the bulk tissue. To highlight its potential, we applied this strategy to study the cellular environment of metastatic breast cancer cells in the lung. We report the presence of cancer-associated parenchymal cells, which exhibit stem-cell-like features, expression of lung progenitor markers, multi-lineage differentiation potential and self-renewal activity. In ex vivo assays, lung epithelial cells acquire a cancer-associated parenchymal-cell-like phenotype when co-cultured with cancer cells and support their growth. These results highlight the potential of this method as a platform for new discoveries.


Assuntos
Linhagem da Célula , Rastreamento de Células/métodos , Metástase Neoplásica/patologia , Células-Tronco Neoplásicas/patologia , Tecido Parenquimatoso/patologia , Coloração e Rotulagem/métodos , Nicho de Células-Tronco , Microambiente Tumoral , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Diferenciação Celular , Técnicas de Cocultura , Células Epiteliais/patologia , Feminino , Humanos , Proteínas Luminescentes/análise , Proteínas Luminescentes/química , Proteínas Luminescentes/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Metástase Neoplásica/imunologia , Neutrófilos/patologia , Organoides/patologia , Nicho de Células-Tronco/imunologia , Microambiente Tumoral/imunologia
15.
BMC Med Imaging ; 19(1): 64, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399078

RESUMO

BACKGROUND: Our aim was to compare CT images from native, nephrographic and excretory phases using image quality criteria as well as the detection of positive pathological findings in CT Urography, to explore if the radiation burden to the younger group of patients or patients with negative outcomes can be reduced. METHODS: This is a retrospective study of 40 patients who underwent a CT Urography examination on a 192-slice dual source scanner. Image quality was assessed for four specific renal image criteria from the European guidelines, together with pathological assessment in three categories: renal, other abdominal, and incidental findings without clinical significance. Each phase was assessed individually by three radiologists with varying experience using a graded scale. Certainty scores were derived based on the graded assessments. Statistical analysis was performed using visual grading regression (VGR). The limit for significance was set at p = 0.05. RESULTS: For visual reproduction of the renal parenchyma and renal arteries, the image quality was judged better for the nephrogram phase (p < 0.001), whereas renal pelvis/calyces and proximal ureters were better reproduced in the excretory phase compared to the native phase (p < 0.001). Similarly, significantly higher certainty scores were obtained in the nephrogram phase for renal parenchyma and renal arteries, but in the excretory phase for renal pelvis/calyxes and proximal ureters. Assessment of pathology in the three categories showed no statistically significant differences between the three phases. Certainty scores for assessment of pathology, however, showed a significantly higher certainty for renal pathology when comparing the native phase to nephrogram and excretory phase and a significantly higher score for nephrographic phase but only for incidental findings. CONCLUSION: Visualisation of renal anatomy was as expected with each post-contrast phase showing favourable scores compared to the native phase. No statistically significant differences in the assessment of pathology were found between the three phases. The low-dose CT (LDCT) seems to be sufficient in differentiating between normal and pathological examinations. To reduce the radiation burden in certain patient groups, the LDCT could be considered a suitable alternative as a first line imaging method. However, radiologists should be aware of its limitations.


Assuntos
Rim/diagnóstico por imagem , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Artéria Renal/diagnóstico por imagem , Urografia/instrumentação , Adulto , Idoso , Meios de Contraste , Feminino , Humanos , Rim/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Tecido Parenquimatoso/diagnóstico por imagem , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/instrumentação , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/instrumentação
16.
PLoS Negl Trop Dis ; 13(8): e0007469, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31465452

RESUMO

As a result of migrations and globalization, people may face a possible increase in the incidence of central nervous system rickettsial infections (CNS R). These diseases, caused by Rickettsia species and transmitted to humans by arthropod bites, are putatively lethal. However, the diagnosis of CNS R is challenging and often delayed due to their nonspecific clinical presentation and the strict intracellular nature of rickettsiae. Furthermore, transfer of rickettsiae to the brain parenchyma is not yet understood. The aim of this review is to analyze and summarize the features and correlated findings of CNS R in order to focus attention on these intriguing but frequently neglected illnesses. We also incorporated data on CNS infections caused by Rickettsia-related microorganisms.


Assuntos
Sistema Nervoso Central/microbiologia , Infecções por Rickettsia/microbiologia , Rickettsia/patogenicidade , Febre Botonosa/microbiologia , Encéfalo , Humanos , Tecido Parenquimatoso/microbiologia , Rickettsia/classificação , Infecções por Rickettsia/epidemiologia , Infecções por Rickettsia/terapia , Infecções por Rickettsia/transmissão , Febre Maculosa das Montanhas Rochosas/microbiologia , Tifo por Ácaros/microbiologia , Rickettsiose do Grupo da Febre Maculosa/microbiologia , Tifo Endêmico Transmitido por Pulgas/microbiologia
17.
Med Oncol ; 36(9): 74, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332543

RESUMO

Hereditary renal cell carcinoma syndromes (HRCCS) are characterized by the presence of pathogenic germline variants that predispose patients to renal cell carcinomas as well as additional extra-renal manifestations. The importance of identifying HRCCS patients cannot be overemphasized, as patients and their families can begin surveillance for syndrome-associated manifestations once identified. The present study is a retrospective clinical and morphologic review of 60 hereditary renal tumors from 30 HRCCS patients treated at our institution with either Von Hippel-Lindau disease (VHL), Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex (TSC), hereditary leiomyomatosis and renal cell cancer syndrome, or succinate dehydrogenase (SDH) deficiency syndrome. Hereditary renal cell carcinoma syndromes kidney tumors often demonstrate specific morphologic features, characteristic background changes in renal parenchyma, and extra-renal manifestations, which, when recognized by the pathologist, can trigger genetic testing referral for specific familial cancer syndromes. Our study demonstrates the majority of tumors were consistent with the anticipated clinicopathologic profile of renal tumors found within HRCCS patients, although we found some unique characteristics within this cohort including a case of clear cell papillary renal cell carcinoma within a VHL patient, and a unique renal tumor with tubulopapillary features present in a patient with a germline SDHD mutation. Additionally, although the literature reports the presence of epithelioid angiomyolipoma (AML) as a common occurrence in TSC patients, our cohort of 3 patients with AMLs demonstrated only classic features. The findings we describe facilitate pathologist-based recognition of HRCCS and can prompt genetic evaluation for relevant patients.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Síndromes Neoplásicas Hereditárias/patologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Criança , Feminino , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/patologia , Doenças Genéticas Inatas/terapia , Humanos , Rim/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/terapia , Tecido Parenquimatoso/patologia , Estudos Retrospectivos , Succinato Desidrogenase/deficiência , Succinato Desidrogenase/genética , Centros de Atenção Terciária , Adulto Jovem
18.
Pathol Int ; 69(9): 536-540, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273873

RESUMO

Upper-lobe predominance of elastofibrosis is agreed upon for the diagnosis of clinical pleuroparenchymal fibroelastosis (PPFE). We herein describe a patient with dermatomyositis-related interstitial pneumonia with a histology of lower-lobe predominant PPFE. A 71-year-old woman who had been diagnosed with dermatomyositis-related interstitial pneumonia died of respiratory failure. The computed tomography patterns of the lower lobes showed reticular and ground-glass opacities with traction bronchiectasis. An autopsy revealed that the bilateral lower lobes were sclerotic with decreased air volume. A microscopic examination of the lower lobes showed pleural fibrosis and subpleural elastofibrosis without the structural destruction, indicative of histological PPFE. PPFE histology was also evident in the upper lobes but relatively modest compared to that of the lower lobes. In addition, because the computed tomography images of the patient were suggestive of non-PPFE-type fibrosis, lower-lobe dominant PPFE might be overlooked in daily practice.


Assuntos
Dermatomiosite/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pleurais/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Corticosteroides/uso terapêutico , Idoso , Autopsia , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Dermatomiosite/patologia , Evolução Fatal , Feminino , Humanos , Imunossupressores/uso terapêutico , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/patologia , Tecido Parenquimatoso/diagnóstico por imagem , Tecido Parenquimatoso/patologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Pleura/diagnóstico por imagem , Pleura/patologia , Doenças Pleurais/complicações , Doenças Pleurais/tratamento farmacológico , Doenças Pleurais/patologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Tadalafila/uso terapêutico , Tomografia Computadorizada por Raios X
20.
Pathol Int ; 69(9): 547-555, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31290582

RESUMO

Pleuroparenchymal fibroelastosis (PPFE) is characterized by upper lobe-predominant subpleural fibroelastosis. Despite its characteristic uneven distribution, detailed whole-lung pathological features of PPFE have rarely been studied. We investigated PPFE in the explanted lungs from a 19-year-old male patient with a history of chemotherapy. Grossly, the explanted lungs showed upper lobe-predominant shrinkage with subpleural and central consolidation. Histologically, fibroelastosis was prominent in the perilobular areas and along the bronchovascular bundles. The other areas of the lung showed diffuse, non-specific interstitial pneumonia (NSIP)-like change with a characteristic increase of septal elastic fibers. In the digital image analysis, the ratio of elastic fibers to whole fibrosis (EF score) was lower in the subpleural areas than in the NSIP-like lesions, but the EF scores of the latter showed no significant difference between upper and middle/lower lobes. In the present case, the diffusely distributed elastic fiber-rich NSIP-like change, probably caused by the earlier chemotherapy, may have been conducive to the development of PPFE. This suggests that some unknown vulnerability of the upper lobe may exist, various primary lesions converging to the upper lobe predominance of PPFE.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Tecido Elástico/diagnóstico por imagem , Tecido Elástico/patologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/patologia , Masculino , Tecido Parenquimatoso/diagnóstico por imagem , Tecido Parenquimatoso/patologia , Pleura/diagnóstico por imagem , Pleura/patologia , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Tomografia Computadorizada por Raios X , Adulto Jovem
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