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1,002 result(s) for "systemic lesions"
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Pathological aspects of disseminated protothecosis-like infection in a dog
Anatomopathological descriptions of infections caused by saprophytic algae in dogs are rare. This study reported the anatomopathological and microbiological findings suggestive of disseminated protothecosis in a dog residing in the state of Espírito Santo, Brazil. During necropsy, macroscopic alterations were observed in peripheral lymph nodes, heart, kidneys, pancreas, and lungs. Microbiological, cytological, and histopathological examinations were performed. Cytology and histopathology revealed piogranulomatous inflammation associated with sporangia and endospores, while microbiological culture suggested the growth of Prototheca spp.. These anatomopathological and microbiological findings were crucial for diagnosing and documenting the first case of disseminated Prototheca spp. compatible infection in a dog in the state of Espírito Santo, Brazil. RESUMO: Descrições anatomopatológicas de infecções causadas por algas saprófitas em cães são raras. Este estudo relata os achados anatomopatológicos e microbiológicos sugestivos de prototecose disseminada em um cão residente no estado do Espírito Santo, Brasil. Durante a necropsia foram observadas alterações macroscópicas em linfonodos periféricos, coração, rins, pâncreas e pulmões. Foram realizados exames microbiológicos, citológicos e histopatológicos. A citologia e a histopatologia revelaram inflamação piogranulomatosa associada a esporângios e endósporos, enquanto a cultura microbiológica sugeriu o crescimento de Prototheca spp. Esses achados anatomopatológicos e microbiológicos foram cruciais para diagnosticar e documentar o primeiro caso de infecção disseminada compatível com Prototheca spp.. estado do Espírito Santo, Brasil.
Modelling of systemic lesion of organism for development of multitarget cellular and cytokine therapy
In recent decades many human pathologies have taken a chronic course. Modern biology and medicine have come to conceptually new therapeutic approaches. The technologies, comprising stem cells and signaling molecules, are the most promising in this respect. They have a potential of restoring systemic lesions, which are the basis of chronicity. To develop these approaches, an adequate and realizable model is required. Here we present an attempt of elaborating such a murine model using CCl4 as an agent, causing systemic lesions.
Cell-free nucleic acid patterns in disease prediction and monitoring—hype or hope?
Interest in the use of cell-free nucleic acids (CFNAs) as clinical non-invasive biomarker panels for prediction and prevention of multiple diseases has greatly increased over the last decade. Indeed, circulating CFNAs are attributable to many physiological and pathological processes such as imbalanced stress conditions, physical activities, extensive apoptosis of different origin, systemic hypoxic-ischemic events and tumour progression, amongst others. This article highlights the involvement of circulating CFNAs in local and systemic processes dealing with the question, whether specific patterns of CFNAs in blood, their detection, quantity and quality (such as their methylation status) might be instrumental to predict a disease development/progression and could be further utilised for accompanying diagnostics, targeted prevention, creation of individualised therapy algorithms, therapy monitoring and prognosis. Presented considerations conform with principles of 3P medicine and serve for improving individual outcomes and cost efficacy of medical services provided to the population.
Radiopacities
A radiopacity is the white area on a conventional radiograph. This chapter overviews the causes of radiopacities of the jaws. It presents the flowcharts, which generally flow from the most important clinical and radiological findings, addressing systemic lesions and malignancies first. Multiple radiopacities, particularly if they are distributed throughout the jaws, suggest a systemic cause, whereas a single radiopacity suggests a local cause. Before considering the two most frequent causes of radiopacities in the jaws, namely dense bone islands (also known as idiopathic osteosclerosis) and sclerosing osteitis, the chapter considers four lesions. These are the adenomatoid odontogenic tumor, calcifying epithelial odontogenic tumor, calcifying odontogenic cyst, and dentinogenic ghost cell tumor. All four present radiologically as containing radiopacities. The first two frequently enclose an unerupted tooth. Although all are very rare, particularly the last three, nevertheless each has provoked the development of considerable bodies of literature, to which the discussion testifies.
Infantile Periocular Hemangioma
Infantile periocular hemangiomas (IPH) are common benign vascular tumors that present early in childhood. They typically show a rapid nonlinear growth pattern a few weeks after birth during a proliferative phase, then continue with an involution phase and may result in serious ocular or systemic complications. Theses tumors may present in a range of small isolated lesions to multiple, diffuse involvements. Understanding the nature of the disease, the natural course, complications, indications for intervention, and treatment modalities would be helpful for ophthalmologists, who will likely be consulted for periocular cases. In this review, we present recent opinions about the pathogenesis, diagnosis, and treatment options for patients with IPH.
Anaphylaxis as a Clinical Manifestation of Clonal Mast Cell Disorders
Clonal mast cell disorders comprise a heterogeneous group of disorders characterized by the presence of gain of function KIT mutations and a constitutively altered activation-associated mast cell immunophenotype frequently associated with clinical manifestations related to the release of mast cells mediators. These disorders do not always fulfil the World Health Organization (WHO)-proposed criteria for mastocytosis, particularly when low-sensitive diagnostic approaches are performed. Anaphylaxis is a frequent presentation of clonal mast cell disorders, particularly in mastocytosis patients without typical skin lesions. The presence of cardiovascular symptoms, e.g., hypotension, occurring after a hymenoptera sting or spontaneously in the absence of cutaneous manifestations such as urticaria is characteristic and differs from the presentation of anaphylaxis in the general population without mastocytosis.
Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus
Plasmacytoid DCs (pDC) produce large amounts of type I IFN (IFN-I), cytokines convincingly linked to systemic lupus erythematosus (SLE) pathogenesis. BIIB059 is a humanized mAb that binds blood DC antigen 2 (BDCA2), a pDC-specific receptor that inhibits the production of IFN-I and other inflammatory mediators when ligated. A first-in-human study was conducted to assess safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) effects of single BIIB059 doses in healthy volunteers (HV) and patients with SLE with active cutaneous disease as well as proof of biological activity and preliminary clinical response in the SLE cohort. A randomized, double-blind, placebo-controlled clinical trial was conducted in HV (n = 54) and patients with SLE (n = 12). All subjects were monitored for adverse events. Serum BIIB059 concentrations, BDCA2 levels on pDCs, and IFN-responsive biomarkers in whole blood and skin biopsies were measured. Skin disease activity was determined using the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A). Single doses of BIIB059 were associated with favorable safety and PK profiles. BIIB059 administration led to BDCA2 internalization on pDCs, which correlated with circulating BIIB059 levels. BIIB059 administration in patients with SLE decreased expression of IFN response genes in blood, normalized MxA expression, reduced immune infiltrates in skin lesions, and decreased CLASI-A score. Single doses of BIIB059 were associated with favorable safety and PK/PD profiles and robust target engagement and biological activity, supporting further development of BIIB059 in SLE. The data suggest that targeting pDCs may be beneficial for patients with SLE, especially those with cutaneous manifestations. ClinicalTrials.gov NCT02106897. Biogen Inc.
Glutathione peroxidase 4–regulated neutrophil ferroptosis induces systemic autoimmunity
The linkage between neutrophil death and the development of autoimmunity has not been thoroughly explored. Here, we show that neutrophils from either lupus-prone mice or patients with systemic lupus erythematosus (SLE) undergo ferroptosis. Mechanistically, autoantibodies and interferon-α present in the serum induce neutrophil ferroptosis through enhanced binding of the transcriptional repressor CREMα to the glutathione peroxidase 4 ( Gpx4 , the key ferroptosis regulator) promoter, which leads to suppressed expression of Gpx4 and subsequent elevation of lipid-reactive oxygen species. Moreover, the findings that mice with neutrophil-specific Gpx4 haploinsufficiency recapitulate key clinical features of human SLE, including autoantibodies, neutropenia, skin lesions and proteinuria, and that the treatment with a specific ferroptosis inhibitor significantly ameliorates disease severity in lupus-prone mice reveal the role of neutrophil ferroptosis in lupus pathogenesis. Together, our data demonstrate that neutrophil ferroptosis is an important driver of neutropenia in SLE and heavily contributes to disease manifestations. Zhang and colleagues identify a role for cell death by glutathione peroxidase 4 (GPX4)-regulated ferroptosis in neutrophils from patients with systemic lupus erythematosus, which is triggered by type I interferons and autoreactive antibodies and contributes to lupus pathogenesis. Inhibiting accumulation of oxidative mediators by GPX4 suppresses ferroptosis.
Automated AI-based image analysis for quantification and prediction of interstitial lung disease in systemic sclerosis patients
Background Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapidly evolving interstitial lung disease (ILD), driving its mortality. Specific imaging-based biomarkers associated with the evolution of lung disease are needed to help predict and quantify ILD. Methods We evaluated the potential of an automated ILD quantification system (icolung ® ) from chest CT scans, to help in quantification and prediction of ILD progression in SSc-ILD. We used a retrospective cohort of 75 SSc-ILD patients to evaluate the potential of the AI-based quantification tool and to correlate image-based quantification with pulmonary function tests and their evolution over time. Results We evaluated a group of 75 patients suffering from SSc-ILD, either limited or diffuse, of whom 30 presented progressive pulmonary fibrosis (PPF). The patients presenting PPF exhibited more extensive lesions (in % of total lung volume (TLV)) based on image analysis than those without PPF: 3.93 (0.36–8.12)* vs. 0.59 (0.09–3.53) respectively, whereas pulmonary functional test showed a reduction in Force Vital Capacity (FVC)(pred%) in patients with PPF compared to the others : 77 ± 20% vs. 87 ± 19% ( p  < 0.05). Modifications of FVC and diffusing capacity of the lungs for carbon monoxide (DLCO) over time were correlated with longitudinal radiological ILD modifications ( r =-0.40, p  < 0.01; r =-0.40, p  < 0.01 respectively). Conclusion AI-based automatic quantification of lesions from chest-CT images in SSc-ILD is correlated with physiological parameters and can help in disease evaluation. Further clinical multicentric validation is necessary in order to confirm its potential in the prediction of patient’s outcome and in treatment management.