ABSTRACT
Background
Ex vivo confocal microscopy is a real-time technique that provides high-resolution images of fresh, non-fixed tissues, with an optical resolution comparable to conventional ...pathology. The objective of this study was to investigate the feasibility of using ex vivo confocal microscopy in fusion mode (FuCM) and the haematoxylin and eosin (H&E)-like digital staining that results for the analysis of basic patterns of lesion in nephropathology.
Methods
Forty-eight renal samples were scanned in a fourth-generation ex vivo confocal microscopy device. Samples were subjected to confocal microscopy imaging and were then processed using conventional pathology techniques. Concordance between the techniques was evaluated by means of the percentage of agreement and the κ index.
Results
Agreement between conventional microscopy and H&E-like digital staining was strong (κ = 0.88) in the evaluation of acute tubular damage and was substantial (κ = 0.79) in the evaluation of interstitial fibrosis, interstitial inflammation, arterial and arteriolar lesions. H&E-like digital staining also allows rapid identification of extracapillary proliferation (κ = 0.88), necrosis and segmental sclerosis (κ = .88) in the glomerular compartment, but the results reported here are limited because of the small number of cases with these glomerular findings.
Conclusions
FuCM proved to be as effective as conventional techniques in evaluating the presence of acute tubular necrosis and interstitial fibrosis changes, but in fresh tissue. The ease of acquisition of ex vivo confocal microscopy images suggests that FuCM may be useful for rapid evaluation of kidney biopsies and to restructure the clinical workflow in renal histopathology.
Lay Summary
This study contributes to the refinement of renal biopsy analysis, showing that ex vivo confocal microscopy can become the first step in a hierarchical study and in the segmentation of kidney biopsy studies in renal medicine. Confocal images correlated very well with the corresponding conventional histological sections. This study opens new methods for the global improvement of renal biopsy analysis, thereby favouring the evaluation of new therapies.
Graphical Abstract
Graphical Abstract
•Treatment of dermatitis skin lesions based on a lipid system that mimics epidermal lamellar bodies.•TEWL, IgE levels and epidermal thickness were reduced after 10 days of topical ...treatment.•Improvement of dermatitis by reinforcing the barrier function and reducing the skin inflammation.
Atopic dermatitis is a common skin disease characterized by a Th2 cell-dominant inflammatory infiltrate, elevated serum IgE levels and impaired epidermal barrier function. It is associated to abnormal epidermal lamellar body secretion, producing alteration in lipid composition and extracellular lamellar membrane organization.
The oxazolone-induced atopic dermatitis in hairless mice was used to evaluate in vivo the effect of the application of a lipid system that mimics the morphology, structure and composition of epidermal lamellar bodies.
The skin barrier function was evaluated measuring TEWL and skin hydration in vivo. Inflammation was assessed by analysis of serum IgE levels and histological analysis. The microstructure of the intercellular lipid region was also evaluated before and after treatment.
The skin condition was improved after 10 days of treatment indicated by decreased TEWL, decreased serum IgE levels, reduced epidermal thickness and reduced lymphocyte-dominated infiltrate. However, the treatment did no improve skin hydration.
The treatment with this lipid system seems to improve the skin condition by reinforcing the barrier function and reducing the skin inflammation. Therefore, the present study provides evidence that this lipid system combining appropriate lipid composition and morphology could be of interest for the development of future treatments for atopic dermatitis.
To define the clinical and pathologic characteristics of primary cutaneous small/medium CD4(+) T-cell lymphoma (PCSM-TCL) and identify parameters of prognostic significance.
We have investigated 24 ...patients with primary cutaneous lymphomas composed of small/medium mature T-cells with a betaF1, CD3, CD4(+) and/or noncytotoxic, CD8(-) and CD30(-) phenotype. The proliferation index and CD8(+) infiltrating cells were quantified with an automated image analysis system.
Sixteen patients presenting with solitary or localized plaques or small nodules (< 3 cm) had an indolent course. Only three patients experienced repeated cutaneous relapses, and none of them died as a result of the disease after 1 to 168 months (median, 17 months) of follow-up. The tumors had a low proliferation (median Ki-67, 9% +/- 5%) and an intense infiltrate of reactive CD8(+) (median, 20% +/- 11.7%). Five patients presenting with rapidly evolving large tumors or nodules (>/= 5 cm) had an aggressive disease and died with extracutaneous dissemination 18 to 36 months after diagnosis (median, 23 months). These tumors had a significantly higher proliferation (median Ki-67, 22% +/- 11.3%; P < .05) and lower number of infiltrating CD8(+) (median, 1% +/- 3%; P < .05) than the previous group. A third group of three patients had a peculiar clinical presentation with multifocal relapsing lesions without extracutaneous dissemination after a long period of follow-up ranging from 41 to 92 months. Histologically, these cases had an intense infiltrate of eosinophils.
PCSM-TCL is a heterogeneous group of tumors with differentiated clinical and pathological characteristics with impact in the outcome of the patients.
Activated BRAF mutations affecting the mitogen-activated protein kinases (MAPK) pathway are present in 50% of metastatic melanomas. Targeted therapies have been developed to block such mutations (1, ...2). There is a risk of other components of the MAPK signalling pathway, such as MEK, being reactivated after the use of BRAF inhibitors (3-5). Given the evidence of drug resistance and side-effects of BRAF inhibitors, combined treatments with BRAF and MEK inhibitors are being tested in clinical trials for metastatic melanoma. Trametinib is one of these MEK inhibitors. Skin toxicities from BRAF inhibitors, such as photosensitivity, palmoplantar keratoderma (PPK) and keratosis pilaris (KP), have been reported (4, 6-11). Also, non-melanoma skin cancers (NMSC) are considered one of the most significant sideeffects (3, 11). We report here the profile of skin toxicities from vemurafenib, dabrafenib alone, or dabrafenib and trametinib combined treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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