Predicting lymphoma in Sjogren's syndrome and the pathogenetic role of parotid microenvironment through precise parotid swelling recording

Objective Parotid swelling (PSW) is a major predictor of non-Hodgkin's lymphoma (NHL) in primary SS (pSS). However, since detailed information on the time of onset and duration of PSW is scarce, this was investigated to verify whether it may lead to further improved prediction. NHL localization was concomitantly studied to evaluate the role of the parotid gland microenvironment in pSS-related lymphomagenesis. Methods A multicentre study was conducted among patients with pSS who developed B cell NHL during follow-up and matched controls that did not develop NHL. The study focused on the history of salivary gland and lachrymal gland swelling, evaluated in detail at different times and for different durations, and on the localization of NHL at onset. Results PSW was significantly more frequent among the cases: at the time of first referred pSS symptoms before diagnosis, at diagnosis and from pSS diagnosis to NHL. The duration of PSW was evaluated starting from pSS diagnosis, and the NHL risk increased from PSW of 2-12 months to >12 months. NHL was prevalently localized in the parotid glands of the cases. Conclusion A more precise clinical recording of PSW can improve lymphoma prediction in pSS. PSW as a very early symptom is a predictor, and a longer duration of PSW is associated with a higher risk of NHL. Since lymphoma usually localizes in the parotid glands, and not in the other salivary or lachrymal glands, the parotid microenvironment appears to be involved in the whole history of pSS and related lymphomagenesis

The farnesoid X receptor: a potential target for expanding the therapeutic arsenal against kidney disease

Introduction: Farnesoid X receptor (FXR) is a nuclear bile acid (BA) receptor widely distributed among tissues, a major sensor of BA levels, primary suppressor of hepatic BA synthesis and secondary regulator of lipid metabolism and inflammation. Chronic kidney disease is a common, multifactorial condition with metabolic and inflammatory causes and implications. An array of natural and synthetic FXR agonists has been developed, but not yet studied clinically in kidney disease. Areas covered: Following a summary of FXR’s physiological functions in the kidney, we discuss its effects in renal disease with emphasis on chronic and acute kidney disease, chemotherapy-induced nephrotoxicity, and renal neoplasia. Most information is derived from animal models; no relevant clinical study has been conducted to date. Expert opinion: Most available preclinical data indicates a promising outlook for clinical research in this direction. We believe FXR agonism to be an auspicious approach to treating renal disease, considering that multifactorial diseases call for ideally wide-reaching therapies. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group

Exosomes in lung cancer diagnosis and treatment. From the translating research into future clinical practice

Lung cancer is one of the main causes of cancer-related death worldwide. Despite advances in lung cancer pathophysiology, diagnosis and prognosis, a better understanding of the disease is strongly needed in order to establish novel diagnostic and therapeutic approaches that should improve treatment outcomes. Exosomes are a type of cell-secreted extracellular vesicles, which transfer a wide variety of biomolecules, such as proteins, mRNAs, microRNAs, and lipids, are implicated in intercellular communication and modulate tumor-host interactions. The potential value of exosomes and their contents in lung cancer diagnosis, prognosis and prediction of treatment outcome is supported by ample literature. Growing attention has been drawn specifically to the critical role of exosomal miRNAs in lung cancer pathogenesis and their potential clinical utility, especially due to their ability to modulate gene expression post-transcriptionally. Owing to their universal presence in the blood and other bodily fluids, exosomes are considered candidate biomarkers. Furthermore, their ability to deliver biomolecules and drugs to recipient cells renders them possible drug delivery vehicles in lung cancer. Here we review the pathological functions of exosomes in cancer and discuss their possible clinical utility as biomarkers and therapeutic agents in the management of lung cancer. © 201

Exosomes in sarcomas: Tiny messengers with broad implications in diagnosis, surveillance, prognosis and treatment

Exosomes are cell-secreted extracellular vesicles, which contain an array of biomolecules, such as proteins, mRNAs, microRNAs, and lipids, take part in intercellular communication and mediate tumor-host interactions. They are increasingly considered as a source of biomarkers for liquid biopsies as well as potential drug vectors. Sarcomas are rare malignant mesenchymal tumours and due to their relative rarity exosomes have not been investigated in as extensively as in epithelial malignancies. Nonetheless, valuable information has been gathered over the last years on the roles of exosomes in sarcomas. In the present review we summarize all relevant data obtained so far from cell lines, animal models and patients with emphasis on their potential clinical utility. © 2019 Elsevier B.V

Exosomes in Nephropathies: A Rich Source of Novel Biomarkers

The biomarkers commonly utilized in diagnostic evaluations of kidney disease suffer from low sensitivity, especially in the early stages of renal damage. On the other hand, obtaining a renal biopsy to augment clinical decision making can lead to potentially serious complications. In order to overcome the shortcomings of currently available diagnostic tools, recent studies suggest that exosomes, cell-secreted extracellular vesicles containing a large array of active molecules to facilitate cell-to-cell communication, may represent a rich source of novel disease biomarkers. Because of their endocytic origin, exosomes carry markers typical for their parent cells, which could permit the localization of biochemical cellular alterations in specific kidney compartments. Different types of exosomes can be isolated from noninvasively obtained biofluids; however, in the context of kidney disease, evidence has emerged on the role of urinary exosomes in the diagnostic and predictive modeling of renal pathology. The current review summarizes the potential application of exosomes in the detection of acute and chronic inflammatory, metabolic, degenerative, and genetic renal diseases. © 2020 Christos Masaoutis et al

Salivary gland cancer in the era of immunotherapy: can we exploit tumor microenvironment?

Introduction: Salivary gland cancers (SGCs) consist of a rare family of neoplasms with varying histology and biological behavior. Therapeutic regimens have been relatively unchanged for decades. The recent successes of immunotherapy have raised hopes for the development of more effective strategies in SGC, thus emphasizing the role of tumor microenvironment (TME) in the design for more effective therapies. Areas covered: This review presents an overview of the current knowledge on the pathobiology of SGC TME and discusses the potential of immunotherapeutic targeting. Expert opinion: Most data on the role of TME in SGC carcinogenesis are derived from preclinical studies. Signaling cascades of immunotherapeutic interest, PD-1/PD-L1 and PD-1/PD-L2, are active in many SGCs and might be associated with biological behavior and prognosis. Immunotherapeutic attempts are very limited, but recent findings in other tumors on the role of exosomes and PD-L2 signaling suggest that TME of SGCs warrants further research, emphasizing larger cohorts, histology-based stratification, and standardized evaluation of immunomodulatory molecules, to explore the potential of targeting tumor stroma and its signaling cascades. Furthermore, combination of immunotherapies or immunotherapies with the antineoplastic agents targeting AR, HER2, and tyrosine kinases, recently introduced in SGC treatment, constitutes a promising approach for the future. © 2020 Informa UK Limited, trading as Taylor & Francis Group

Differential immunohistochemical expression of hTERT in lung cancer patients with and without idiopathic pulmonary fibrosis

Background: Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase enzyme, which adds nucleotides to telomeres and counteracts their length shortening. The development of a telomere maintenance mechanism represents a hallmark of cancer. On the other hand, idiopathic pulmonary fibrosis (IPF) is associated with mutations in telomerase genes and shorter telomeres. IPF is frequently complicated with lung cancer. Aim: To investigate the expression of hTERT in lung cancer with co-existing IPF and to compare with lung cancer without fibrosis. Methods: Diagnostic lung cancerous biopsies were retrieved from 18 patients with lung cancer and concomitant IPF, as well as 18 age and gender matched controls with lung cancer without pulmonary fibrosis. The expression of hTERT was studied with immunohistochemistry. ImajeJ software was used to quantitate subcellular stain intensity. Immunohistochemical investigation of two senescence-associated markers, p16 and p21, was also performed in all 36 cases. Results: Both groups highly expressed hTERT, without significant difference (100% vs 95%, p = 0.521). Evaluation of p16 and p21 immunostaining revealed negative to minimal immunoreactivity in both groups. hTERT localization exhibited higher median nuclear intensity in the group of lung cancer with IPF (0.62 vs 0.45, p = 0.016), while cytoplasmic intensity did not differ significantly (0.17 vs 0.15, p = 0.463). Higher median nuclear intensity was also correlated with small cell lung cancer subtype in the whole study sample (0.69 vs 0.45, p = 0.09). Conclusion: hTERT is highly expressed in lung cancer with concomitant IPF, but with differential localization compared to lung cancer without IPF, implying differences in pathogenicity and requiring further investigation. © 2022 Sociedade Portuguesa de Pneumologi

The role of fundus autofluorescence imaging in the study of the course of posterior uveitis disorders

Background. To evaluate the correlation of fundus autofluorescence (FAF) with indocyanine green angiography (ICGA) in patients with various posterior uveitis disorders. Methods. Interventional case series including 23 eyes of 15 patients with diagnosis of a specific type of retinochoroiditis, such as acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous-like choroiditis, multifocal choroiditis (MFC), Harada disease, and syphilitic retinochoroiditis. Also, some cases with undefined retinochoroiditis were included. FAF and ICGA were performed and correlated at baseline and during follow-up after treatment. Results. In ICGA, early hypofluorescence was found to be the hallmark of acute choroidal inflammation, resolving in later stages and remaining in the late phase in areas with retinal pigment epithelium (RPE) damage. Poorly defined hyperautofluorescent areas correlated with acute choroidal lesions. Hypoautofluorescent delineation suggested the initiation of RPE healing processes, correlating well with the late phase of ICGA and delineating the RPE damage. Early hyperautofluorescence with late hypofluorescence in ICGA indicated the presence of primary RPE involvement. Conclusion. FAF contributes to the interpretation of RPE disease and may be a useful tool for the follow-up of progressive inflammatory disorders. Comparative evaluation of FAF and ICGA allows a characterization of the sequence of inflammatory events and the level of tissue affected. Copyright © 2015 Panagiotis Malamos et al

Pulmonary nocardiosis associated with Cushing's disease: A case report

Nocardia spp. is a genus of Gram-positive bacteria which can cause cutaneous, pleuropulmonary, or disseminated disease. The latter two forms are encountered in immunocompromised patients, with prolonged usage of corticosteroids being a well-recognized risk factor. However, endogenous Cushing’s syndrome is less frequently associated with nocardiosis. We report on a 40-year-old woman who presented for further workup of abnormal findings in the chest computed tomography (three lung nodules, one of which being cavitary). She underwent trans-thoracic fine-needle lung aspiration of the cavitary nodule, which led to the diagnosis of lung nocardiosis. Moreover, the identification of cushingoid features from the history and clinical examination initiated further investigation with hormonal laboratory assessment and bilateral inferior petrosal sinus sampling which established the diagnosis of pituitary adrenocorticotropic hormone (ACTH) hypersecretion (Cushing’s disease). We conclude that pulmonary nocardiosis can be an opportunistic infection as well as a presenting manifestation of Cushing’s disease. ©Copyright: the Author(s), 2019