Epithelial Atrophy Research Articles

Antibiotic Susceptibility Profile of Bacteria Causing Aerobic Vaginitis in Women in Iraq.

Aerobic vaginitis (AV) is a vaginal infectious condition characterized by abnormal vaginal discharge, high inflammatory response, signs of epithelial atrophy, an increase in aerobic bacteria of intestinal origin and a decrease in the normal flora, especially Lactobacillus spp.. It is one of the most common reproductive tract infections among women. This study aimed to analyze the antimicrobial susceptibility levels of the dominant bacterial species found in the vaginae of women infected with AV. A total of 89 high vaginal swabs (HVS) were collected from women aged (18-50) years old attending some hospitals and private gynaecology clinics in Baghdad City. All obtained swabs were cultured on different culture media, and the primary diagnosis was performed according to standard laboratory diagnosis protocols. To confirm the diagnosis and to determine the antibiotic susceptibility profile of bacterial isolates, VITEK 2 Compact Automated System GP and GN colourimetric identification cards and AST GN and AST GP cards were used according to Manufacturer Company constructions (BioMérieux / France). Out of 89swabs, ninety-five pathogenic strains were obtained, including 62 isolates (65.2%), Grampositive and 33 isolates (34.7%), Gram-negative bacteria. Staphylococcus spp. (46.3%) The most represented active strain was Escherichia coli (15.7%). All Gram-positive bacterial strains displayed the highest resistance rates (100%) toward penicillins and cephalosporins, while the highest sensitivity rates were toward daptomycin, followed by vancomycin and gentamicin (P=0.001). Gram-negative bacteria displayed the highest resistance rates toward penicillins, beta-lactam combination, monobactam and cephalosporins, while the highest sensitivity rates were toward amikacin followed by imipenem meropenem and gentamicin (P=0.001). It is worth mentioning that Gram-positive bacteria showed 100% sensitivity toward tigecycline. Thirty-eight (40 %) of all obtained bacterial strains were extensively drug-resistant XDR, 57 (60%) were multidrug resistance MDR and no pan-drug resistance PDR was reported. Gram-positive bacteria include 21% XDR and 44.2% MDR strains, while Gram-negative bacteria include 18.9% XDR and 15.7% MDR strains.

Gastrodin attenuates renal injury and collagen deposition via suppression of the TGF-β1/Smad2/3 signaling pathway based on network pharmacology analysis.

Background: Gastrodin has been widely used clinically in China as an antihypertensive drug. However, its effect on hypertensive renal injury is yet to be elucidated. The current study aimed to investigate the effects of gastrodin on hypertensive renal injury and its underlying mechanisms by network pharmacology analysis and validation in vivo and in vitro. Methods: A total of 10 spontaneously hypertensive rats (SHRs) were randomly categorized into the following two groups: SHR and SHR + Gastrodin groups. Wistar Kyoto (WKY) rats were used as the control group (n = 5). The SHR + Gastrodin group was intragastrically administered gastrodin (3.5mg/kg/day), and the rats in both WKY and SHR groups were intragastrically administered an equal amount of double-distilled water for 10 weeks. Hematoxylin-eosin, Masson's trichrome, and Sirius red staining were used to detect the pathological changes and collagen content in the renal tissues. Network pharmacology analysis was performed to explore its potential targets and related pathways. In vitro, the CCK-8 assay was used to determine the cell viability. Immunohistochemistry and western-blotting analyses were employed to assess the protein expression associated with renal fibrosis and transforming growth factor-β1 (TGF-β1) pathway-related proteins in the renal tissues or in TGF-β1-stimulated rat kidney fibroblast cell lines (NRK-49F). Results: Gastrodin treatment attenuates renal injury and pathological alterations in SHRs, including glomerular sclerosis and atrophy, epithelial cell atrophy, and tubular dilation. Gastrodin also reduced the accumulation of collagen in the renal tissues of SHRs, which were confirmed by downregulation of α-SMA, collagen I, collagen III protein expression. Network pharmacology analysis identified TGFB1 and SMAD2 as two of lead candidate targets of gastrodin on against hypertensive renal injury. Consistently, gastrodin treatment downregulated the increase of the protein expression of TGF-β1, and ratios of both p-Smad2/Smad2 and p-Samd3/Smad3 in renal tissues of SHRs. In vitro, gastrodin (25-100μM) treatment significantly reversed the upregulation of α-SMA, fibronectin, collagen I, as well as p-Smad2 and p-Smad3 protein expressions without affecting the cell viability of TGF-β1 stimulated NRK-49F cells. Conclusion: Gastrodin treatment significantly attenuates hypertensive renal injury and renal fibrosis and suppresses TGF-β1/Smad2/3 signaling in vivo and in vitro.

Lactate-induced mtDNA Accumulation Activates cGAS-STING Signaling and the Inflammatory Response in Sjögren's Syndrome.

Acinar epithelial cell atrophy in secretory glands is a hallmark of primary Sjögren's syndrome (pSS), the cause of which is far from elucidated. We examined the role of acinar atrophy by focusing on the metabolism of glandular epithelial cells and mitochondria in the pSS environment. After confirming the presence of a high-lactate environment in the labial glands of human pSS patients, we used the A253 cell line and NOD/Ltj mice as models to investigate the metabolic changes in salivary gland epithelial cells in a high-lactate environment in vitro and in vivo. We found that epithelial cells produced high levels of IL-6, IL-8, IFN-α, IFN-β and TNF-α and exhibited significant NF-κB and type I IFN-related pathway activation. The results confirmed that lactate damaged mitochondrial DNA (mtDNA) and led to its leakage, which subsequently activated the cGAS-STING pathway. Inflammatory cytokine production and pathway activation were inhibited in vivo and in vitro by the lactate scavenger sodium dichloroacetate (DCA). Our study provides new insights into the etiology and treatment of pSS from the perspective of cell metabolism.

Sjögren's Syndrome Treatments in the Microbiome Era.

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by inflammatory cell infiltration of the salivary and lacrimal glands, resulting in acinar epithelial cell atrophy, cell death, and loss of exocrine function. At least half of SS patients develop extraglandular inflammatory disease and have a wide range of systemic clinical manifestations that can affect any organ system, including connective tissues. As many as 3.1 million people in the U.S. suffer from SS, a disease that causes severe impairment. Women are nine times more likely than men to be affected by this condition. Unfortunately, there is currently no effective treatment for SS, and the available options only provide partial relief. Treatment involves using replacement therapies such as artificial saliva and eye lubricants, or immunosuppressive agents that have limited efficacy. The medical community recognizes that there is a significant need for more effective treatments for SS. Increasing evidence demonstrates the links between the dysfunction of the human microbial community and the onset and development of many human diseases, signifying the potential use of microorganisms as an alternative strategy to conquer these issues. The role of the microbiome in controlling immune function of the human host in the context of autoimmune diseases like SS is now becoming better understood and may help to enable new drug development strategies. Natural probiotics and synthetic biology applications hold promise for novel treatment approaches to solve the encryption of many complex and multifactorial immune disorders, like SS.

Oral Immune-Related Adverse Events Associated with PD-1 Inhibitor Treatment: A Case Series

Introduction: Immune Checkpoint Inhibitor (ICI) drugs have led to a revolution in the treatment of different forms of cancer, shifting the target of action from cancer cells to the patient’s immune system, enhancing their responses against the tumor itself. On the other hand, this mechanism can lead to responses against oneself, with the appearance of immune-related adverse events. The aim of the present study was to examine the immune-related adverse events (irAEs) affecting the mucous membranes of the oral cavity and the possible correlation between these and skin toxicities, which are reported in the literature as the most common adverse events. Materials and methods: Thirteen patients treated with anti-Programmed Death (PD-1) drugs (pembrolizumab, nivolumab, and cemiplimab) were selected. The data collected include the general history of the patient and the type of anticancer treatment. The sample was then analyzed by recording the alterations found on the mucous membranes of the oral cavity and on the skin. Finally, the average time that elapsed between the start of immunotherapy and the onset of lesions was analyzed. Results: Patients often had multiple lesions at the same time. Hyperkeratosis was found in three patients, candidiasis (pseudomembranous and median rhomboid glossitis) in two patients, epithelial atrophy in four patients, and ulcerative areas in two patients. One patient reported xerostomia with dysphagia. The anatomical areas most involved were the dorsal tongue and palate. Skin irAEs included skin rash erythema (n = 7) with diffuse redness, the presence of small bubbles with a crusty outcome, and dryness of the skin in the affected areas. Discussion: In the literature, there are few studies that analyze how irAEs affect the mucous membranes of the oral cavity in patients treated with ICI drugs. The most frequently described lesions are lichenoid reactions and xerostomia. Moreover, the development of mucositis, generally of low grade, has been reported. The present study has confirmed the data from the literature and, in addition, reports two cases of candidiasis, an adverse event that has never been shown in the literature. Conclusions: irAEs have the potential to affect any organ. The only way to avoid the occurrence of serious events that is currently available is early interception, which is only possible through the knowledge of these manifestations. It is therefore considered necessary to deepen our knowledge of oral irAEs and their correlation with dermatological toxicities, allowing for a multidisciplinary classification of the patient and a timely diagnosis of any adverse event and avoiding progression to more advanced stages, which could lead to the temporary or permanent suspension of anticancer drugs.

Evaluation of poly(N-isopropylacrylamide)/tetraphenylethylene/amphotericin B-based visualized antimicrobial nanofiber wound dressing for whole skin wound healing in rats

The aim of this work is to develop a novel nanofiber wound dressing with multiple functional properties that combines suitable mechanical properties, slow and controlled drug release, antifungal activity, and visual drug monitoring to accelerate wound healing while reducing systemic circulation of the drug, achieving reduced dose and side effects, and achieving patient satisfaction and compliance. In this paper, visualized nanofiber films were prepared using electrostatic spinning technology. This nanofiber wound dressing has soft tissue-like mechanical and antifungal properties and is biocompatible. In particular, the poly(N-isopropylacrylamide) (PNIPAAm)/tetraphenylethylene (TPE)/amphotericin B (AMB) nanofiber films showed good performance in terms of antifungal activity and cytocompatibility compared with medical gauze, and significantly accelerated the wound healing process in a mouse total wound defect model with PCL+PVP+TPE+AMB+PNIPAAm. The wound healing rate of nanofibrous membrane group was 100% at 14 days. In addition, histological analysis, collagen deposition and immunohistochemistry showed, for example, fewer inflammatory cells, more fibroblasts around the damaged area, increased wound epithelial atrophy, reduced granulation tissue, connective tissue reconstruction, epithelial tissue formation, and abundant small angiogenesis in the dermis near the epidermis; a higher level of collagen deposition fraction of 49.97%; and a simultaneous reduction in HIF-1α production and upregulated the expression of CD31. In conclusion, this antifungal nanofiber film showed promising applications throughout the skin wound healing process.

Formulation of in-Vivo Experimental Model of Oral Submucous Fibrosis in Wistar Rat

Background: Oral submucous fibrosis is a chronic, fibrotic and crippling disease that affects the oral mucosa. It leads to progressive fibrosis that mainly involves the buccal mucosa but other parts of the oral cavity such as the tongue and palate can also be affected. There is a general consensus that areca nut and its constituents are mainly responsible for the pathogenesis of the disease. On histological examination of a biopsy taken from the human oral mucosa, OSMF presents with atrophic epithelium and juxta-epithelial deposition of a vast amount of collagen. Material and Methods:12 healthy male Wistar rats (age 5-6 weeks) were divided into two groups: group A (control) and group B (experimental) after ethical approval. Bleomycin is an anti-cancer drug that is used to create various animal models of fibrosis. In this study, bleomycin was injected into the buccal mucosa of Wistar rat at a concentration of 1mg/mL dissolved in 0.01 M phosphate-buffered saline (PBS) for 4-8 weeks daily. The control group was treated with normal saline. Body weight and mouth openings were recorded. A macroscopic examination was done along with a microscopic analysis of histopathological features and an immunohistochemical analysis of α-SMA expression. Masson’s trichrome stain was used to visualize the collagenous deposition in sub-epithelial tissue. Results: Clinically buccal mucosa showed lesions that mimicked OSMF. Changes in epithelium and lamina propria were observed in the experimental group as compared to the control group. At week 4, stratified squamous epithelium of buccal mucosa showed shortening of rete ridges and lamina propria showed deposition of thick separate collagen. At week 8, epithelium became flat, and atrophic with loss of rete ridges and lamina propria showed juxta-epithelial deposition of collagen which was completely hyalinized and α-SMA expression increased in myofibroblasts. Conclusion: The results from our study suggested that Wistar rats are a reproducible and sustainable model for OSMF. Keywords: Oral submucous fibrosis, animal model, bleomycin, fibrosis, alpha-smooth muscle actin

Chronic Ulcerative Stomatitis (CUS) as an Interdisciplinary Diagnostic Challenge: A Literature Review.

Chronic ulcerative stomatitis (CUS) is a rarely reported disease affecting the oral cavity, most often affecting middle-aged Caucasian females. The aim of the present study is to present the diagnosis, differentiation, and interdisciplinary treatment of this rare disease. CUS is characterized by the presence of an oral erosive or ulcerative lesion. The autoimmune pathogenesis of CUS includes affecting the antigen's activity by DNA-breaking and protein-hydrolyzing enzymes. The stratified epithelium-specific antinuclear antibodies (SES-ANA) are associated with CUS development. Clinically, the lesions presented in oral mucosa might resemble an erosive form of oral lichen planus, whereas gingival lesions seem to be similar to desquamative gingivitis related to dermatological diseases manifested in the oral cavity. Patients often report subjective symptoms related to oral mucosa and general symptoms. Histopathological presentation of CUS is often non-specific and includes sub-epithelial separation from underlying connective tissue, atrophic epithelium, and inflammatory infiltrate with an increased number of plasma cells and lymphocytes. Direct immunofluorescence (DIF) might be used in CUS diagnostics. CUS generally remains nonsusceptible to corticosteroid treatments; however, antimalarial drugs and calcineurin inhibitors are more effective. Further research should be conducted in order to implement a diagnostic protocol and observe the long-term results of CUS management.

Impact of intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell and nerve fibre layer thickness in Neovascular age-related macular degeneration.

To compare the effects of monotherapy with intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell layer (RGCL) and retinal nerve fibre layer (RNFL) in patients with naïve neovascular age-related macular degeneration (nAMD). This is a retrospective cohort study with three-groups comparison. 83 patients and 97 eyes on continuous monotherapy with an intravitreal anti-vascular endothelial growth factor (anti-VEGF) were followed for 24 months and divided into three groups according to anti-VEGF (aflibercept: 25 eyes, ranibizumab: 34 eyes, bevacizumab: 38 eyes). Main outcome measures included: RGCL and RNFL thickness, best corrected visual acuity (BCVA), central macular thickness (CMT), macular volume (MV) and the presence of intraretinal fluids (IRF), subretinal fluids (SRF) and retinal pigment epithelial atrophy (RPE-atrophy). All outcome measures were recorded at the time of the first injection, 1 and 2 years after treatment and compared longitudinally and between groups. The mean age was 79 ± 7 years. The RGCL thickness, MV, CMT and the presence of IRF and SRF decreased significantly within all three medication groups (p < 0.05 for all) with no significant difference between groups over the 2-year follow-up period (p > 0.10 for all). The decrease in RNFL thickness was not significant within or between the groups after a 2-year follow-up (p > 0.055 for all). RPE-atrophy increased significantly after 2 years in all three groups (p < 0.028 for all) with no significant difference between groups at all three time points (p > 0.307 for all). BCVA was comparable between the three groups over the 2-year follow-up period (p > 0.22 for all). Monotherapy with intravitreal aflibercept, bevacizumab and ranibizumab was associated with comparable significant decreases in RGCL thickness, CMT, MV, IRF and SRF in naïve nAMD patients during the first 2 years of treatment. Furthermore, no significant differences either in BCVA or RNFL thickness were observed between the three intravitreal anti-VEFGs during the first 2 years of treatment.

MELTF Might Regulate Ferroptosis, Pyroptosis, and Autophagy in Platelet-Rich Plasma-Mediated Endometrial Epithelium Regeneration.

The endometrial basal layer is essential for endometrial regeneration, whose disruption leads to thin endometrium or intrauterine adhesion (IUA) with an unsatisfactory prognosis. Emerging data indicate that platelet-rich plasma (PRP) can promote endometrial proliferation, but the mechanism by which PRP regulates endometrial regeneration remains unclear. Herein, we investigated the therapeutic effects and possible mechanisms of PRP on endometrial regeneration. IUA animal model was generated by sham, mechanically damaging endometrium with or without PRP for 10days. The uterine section in the model group showed degenerative changes with a narrow endometrial lumen, atrophic columnar epithelium, decreased number of endometrial glands, decreased endometrial thickness, and increased collagen deposition. The above disruption could be ameliorated by the PRP. Transcriptome sequencing analysis displayed that the retinol metabolism pathway and extracellular matrix (ECM) receptor interaction pathway were up-regulated and enriched in differential expression genes (DEGs). Melanotransferrin (MELTF) was the key up-regulated gene in PRP-induced endometrial regeneration, which was verified in vivo and in vitro. Ferroptosis, autophagy, and pyroptosis were down-regulated in PRP-treated Ishikawa cells. Conclusively, PRP promotes endometrium regeneration by up-regulating the retinol metabolism and ECM receptor interaction pathway with MELTF. Meanwhile, PRP could also inhibit endometrial epithelial cell death by regulating ferroptosis, autophagy, and pyroptosis.

A Clinicohistopathological Characterization of Oral Lichen Planus: A Cross-Sectional Study.

Based on the modified diagnostic criteria for oral lichen planus (OLP) proposed by Van der Meij and Van der Waal, the objective of the current investigation was to demonstrate a clinicohistopathological association in the diagnosis of OLP. Data were retrieved from 250 individuals who visited the Department of Oral Medicine and Radiology and were diagnosed with OLP between September 2018 and December 2021. Upon completion of the histopathological analysis, the precise diagnosis of OLP was made. Repeat biopsies were performed in the cases suspecting malignant transformation during the follow-up phase. The data were analyzed using SPSS software. The Fisher's exact test and chi-square test of association were used to establish the significant differences between the variables at a 5% significance level. Of the 250 patients, 48% and 52% were males and females, respectively. The two clinical manifestations observed were reticular (n=145, 58%) and erosive types (n=105, 42%). The most frequently impacted locations were the buccal mucosa (n=150, 60%) and labial mucosa (n=100, 40%). Fourteen individuals (two with reticular form and 12 with erosive form) later during follow-up showed dysplasia, with moderate (n=2) to mild (n=12) dysplastic alterations. Koilocytes were reported in 84 cases (34%), which included 35 (24%) reticular cases and 49 (47%) erosive lesions. The histopathological features such as acanthosis, epithelial atrophy, hyperkeratosis, presence of neutrophils, koilocytes, and epithelial dysplasia were shown to be statistically significant between the clinical forms (p<0.001). The results of the current study highlight the concordance of histopathological and clinical diagnoses, especially for early definitive diagnosis of OLP. More research studies are warranted to validate the trend of epithelial dysplasia in OLP associated with human papillomavirus (HPV) and to explore the course of the lesions that might be affected by this trait.

Multimodal imaging of the course of retinal changes in acute posterior multifocal placoid pigment epitheliopathy with bilateral retinal detachment: a case report

BackgroundTo report a rare case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) with a combination of serous retinal detachment, papilledema, and retinal vasculitis.Case presentationA 19-year-old male complained of floaters in both eyes with decreased vision for 4 days. The best corrected visual acuity of the right eye and the left eye were 1.1 and 0.9 (logMAR), respectively. In both eyes, inflammatory cells can be seen suspended within the vitreous, multiple yellow/white lesions can be seen near the macula, and retinal neuroepithelial detachment. Swelling of the optic disc with blurring of the disc margins, in the left eye. Optical coherence tomography (OCT): showed retinal detachment in both eyes. The patient received oral prednisone treatment. 1 week later, OCT showed absorption of subretinal fluid in the macula of both eyes his binocular vision improved to 0.1 (logMAR). During the subsequent 28-month follow-up, fundus fluorescein angiography and OCT revealed extensive and progressive pigment epithelial atrophy in both eyes, and abnormal retinal vascular perfusion in the right eye due to persistent retinal vasculitis. Although the patient's binocular visual acuity remained at 0.1 (logMAR).ConclusionsIn the present case of APMPPE with a combination of serous retinal detachment, papilledema, and retinal vasculitis, through the multimodal imaging, further confirming that the lesions were located in the choroid, while the pigment epithelial lesions were secondary changes.

Density Functional Model of Raman Spectra for the Seminiferous Tubules of Hindlimb Unloaded Mice

A model Raman spectrum was constructed by using density functional theory (DFT) to track amino acid changes in the seminiferous tubules of hindlimb unloaded (HU) mice. A B3LYP functional with 6-31G* polarization basis sets were used in the calculations. A number of features in the model were comparable to the experimentally obtained spectrum collated with a 785-nm laser from the testicular tissues of the male mice unloaded for two weeks. A comparison of the theoretical and the experimental Raman spectra indicated that hydroxyproline and tryptophan are the major amino acids in the seminiferous tubules. By using Raman spectroscopy, we also confirmed by histological measurement that the same molecules showed depression. The changes in these molecules resulted in the disruption of the testicular seminiferous tubules, resulting in pathological conditions such as epithelial atrophy, tubular shrinkage, and lumen expansion. Our observations indicated that the DFT model of the Raman spectra has the potential to precisely predict and analyze the features of the experimental spectra in the testicular tissues of HU mice.

The multifaceted role of kidney tubule mitochondrial dysfunction in kidney disease development.

More than 800 million people suffer from kidney disease. Genetic studies and follow-up animal models and cell biological experiments indicate the key role of proximal tubule metabolism. Kidneys have one of the highest mitochondrial densities. Mitochondrial biogenesis, mitochondrial fusion and fission, and mitochondrial recycling, such as mitophagy are critical for proper mitochondrial function. Mitochondrial dysfunction can lead to an energetic crisis, orchestrate different types of cell death (apoptosis, necroptosis, pyroptosis, and ferroptosis), and influence cellular calcium levels and redox status. Collectively, mitochondrial defects in renal tubules contribute to epithelial atrophy, inflammation, or cell death, orchestrating kidney disease development.

Non-neovascular fluid in age-related macular degeneration: observe-and-extend regimen in a case-series study

ObjectifDécrire l’évolution du liquide non néovasculaire dans la dégénérescence maculaire liée à l’âge (DMLA) après l'administration d'anti-VEGF (facteur de croissance endothélial vasculaire) ou après une période d'observation sans injection. NatureÉtude rétrospective portant sur une série de cas. MéthodesOnt été inclus des yeux qui présentaient une DMLA s'accompagnant de drusens maculaires et/ou d'un décollement drusénoïde de l’épithélium pigmentaire associée à l'apparition d'un liquide non néovasculaire. On a réalisé une angiographie-tomographie par cohérence optique (OCTA) dans tous les yeux afin d'exclure la présence d'une néovascularisation maculaire. Le liquide sous-rétinien (LSR) a été mesuré afin de déterminer la réponse à la suite de l'administration d'anti-VEGF et après une période d'observation sans injection. RésultatsAinsi, 10 yeux de 9 patients qui présentaient une DMLA intermédiaire s'accompagnant de LSR ont été étudiés pendant une médiane de 59,5 mois (fourchette : 7–128 mois). De ce nombre, 6 patients (6 yeux) avaient déjà reçu un anti-VEGF. La durée médiane du suivi sans injection était de 13,5 mois (fourchette : 4–44 mois). L’épaisseur du LSR est demeurée stable et n'a pas changé pendant le suivi sans injection dans tous les yeux (n = 6) qui avaient reçu des injections et dans tous les yeux (n = 4) qui n'avaient jamais reçu d'injection. Par ailleurs, on a observé une atrophie complète de l’épithélium pigmentaire rétinien (EPR) et des couches externes de la rétine dans 6 yeux, tandis qu'on a noté une atrophie incomplète de l'EPR et des couches externes de la rétine dans 1 seul œil. Tous les yeux présentaient au moins 2 biomarqueurs visibles à l'OCT et associés à un risque élevé de progression vers l'atrophie. ConclusionNotre étude fournit des données préliminaires sur la progression du liquide non néovasculaire dans la DMLA, avec ou sans injection d'anti-VEGF. L'apparition de liquide pourrait tenir à une dysfonction de la pompe de l'EPR. Il est essentiel de faire la distinction entre le liquide néovasculaire et le liquide non néovasculaire par l'intermédiaire de techniques d'imagerie multimodale, notamment l'OCTA, pour éviter d'administrer inutilement un anti-VEGF. On peut envisager un regime « d'observation-et-extension » (observe-and-extend) en présence de DMLA qui s'accompagne d'un liquide non néovasculaire.

Incomplete Retinal Pigment Epithelial and Outer Retinal Atrophy: Longitudinal Evaluation in Age-Related Macular Degeneration

To examine the association between incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) on OCT imaging and the subsequent risk of developing geographic atrophy (GA) defined on conventional color fundus photography (CFP) and to compare this with the specific features that define nascent GA (nGA). Retrospective analysis of data from a longitudinal study. A total of 280 eyes from 140 participants with bilateral large drusen without specific nGA-defining features or late age-related macular degeneration (AMD) at baseline. OCT imaging and CFP were performed at baseline and then at 6-month intervals for up to 36 months. Eyes that developed neovascular AMD were censored on the day it was detected. OCT volume scans were graded for the presence of iRORA and nGA separately, and CFP images were graded for the presence of GA. Association with and variance explained in time to GA development. A total of 58 eyes (21%) from 46 participants (33%) had iRORA at baseline, and a further 87 eyes (31%) developed iRORA over the follow-up period. Time-to-event analyses demonstrated that prevalent orincident iRORA was associated with an increased rate of GA development (adjusted hazard ratio [HR], 12.1; P= 0.021), as was incident nGA (adjusted HR, 78.6; P < 0.001). However, only the specific nGA features (adjusted P < 0.001), and not iRORA (adjusted P= 0.520), were associated with an increased rate of GA development when both features were included in the same multivariable model. The proportion of variance explained in the time to GA development by iRORA itself (R2= 43%) was significantly lower than explained by nGA alone (R2= 91%; P= 0.010). In this cohort, iRORA is a significant risk factor for GA development, but its association with GA development appears to be accounted for by the development of the specific features that define nGA. Although requiring replication, these findings provide useful guidance on the relative utility of nGA and iRORA as risk factors for GA and as potential surrogate end points for future interventional studies in the early stages of AMD.

Automated Identification of Incomplete and Complete Retinal Epithelial Pigment and Outer Retinal Atrophy Using Machine Learning

To assess and validate a deep learning algorithm to automatically detect incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) and complete retinal pigment epithelial and outer retinal atrophy (cRORA) in eyes with age-related macular degeneration. In a retrospective machine learning analysis, a deep learning model was trained to jointly classify the presence of iRORA and cRORA within a given B-scan. The algorithm was evaluated using 2 separate and independent datasets. OCT B-scan volumes from 71 patients with nonneovascular age-related macular degeneration captured at the Doheny-University of California Los Angeles Eye Centers and the following 2 external OCT B-scans testing datasets: (1) University of Pennsylvania, University of Miami, and Case Western Reserve University and (2) Doheny Image Reading Research Laboratory. The images were annotated by an experienced grader for the presence of iRORA and cRORA. A Resnet18 model was trained to classify these annotations for each B-scan using OCT volumes collected at the Doheny-University of California Los Angeles Eye Centers. The model was applied to 2 testing datasets to assess out-of-sample model performance. Model performance was quantified in terms of area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC). Sensitivity, specificity, and positive predictive value were also compared against additional clinician annotators. On an independently collected test set, consisting of 1117 volumes from the general population, the model predicted iRORA and cRORA presence within the entire volume with nearly perfect AUROC performance and AUPRC scores (iRORA, 0.61; 95% confidence interval [CI] [0.45, 0.82]: cRORA, 0.83; 95% CI [0.68, 0.95]). On another independently collected set, consisting of 60 OCT B-scans enriched for iRORA and cRORA lesions, the model performed with AUROC (iRORA: 0.68, 95% CI [0.54, 0.81]; cRORA: 0.84, 95% CI [0.75, 0.94]) and AUPRC (iRORA: 0.70, 95% CI [0.55, 0.86]; cRORA: 0.82, 95% CI [0.70, 0.93]). A deep learning model can accurately and precisely identify both iRORA and cRORA lesions within the OCT B-scan volume. The model can achieve similar sensitivity compared with human graders, which potentially obviates a laborious and time-consuming annotation process and could be developed into a diagnostic screening tool.

IMMUNOHISTOCHEMICAL EXPRESSION OF METALLOPROTEINASES AND TFN-Α BY MACROPHAGES AND LANGERHANS CELLS IN RADICULAR CYSTS

Objectives This research aimed to evaluate the relationship between Langerhans cells, macrophages, matrix metalloproteinases (MMPs-9, -13), and tumor necrosis factor (TNF)-α in the lining epithelium of cystic lesions to elucidate the cyst expansion. Study Design A sectional and retrospective study was performed with 20 radicular cysts (RCs) and 20 residual radicular cysts (RRCs) by anti-CD68, anti-CD1a, anti-MMP-9, anti-MMP-13, and anti-TNF-α antibodies. Results The immunoexpression of MMP-13 and CD68 was significantly higher in RCs when compared to RRCs (P = .011 and P = .012, respectively). An intense inflammatory infiltrate was significantly correlated with CD68 immunoexpression in RCs (P = .025). Macrophages demonstrated a significant positive correlation with MMP-13 (P = .015). A moderate correlation was observed between MMP-9 and MMP-13 (P = .01). TNF-α expression was more common in RCs (P = .001). Langerhans cells were more frequently expressed in atrophic epithelium (P = .041) and significantly correlated with TNF-α (P = .014) in RCs. Conclusions Macrophages induce a greater release of TNF-α. Higher immunoexpression of MMP-13 and MMP-9 is observed in the early stages of RCs compared to RRCs. The microorganisms are the main factors triggering a proinflammatory immune response and greater cystic expansion in the early stages of these cysts. This research aimed to evaluate the relationship between Langerhans cells, macrophages, matrix metalloproteinases (MMPs-9, -13), and tumor necrosis factor (TNF)-α in the lining epithelium of cystic lesions to elucidate the cyst expansion. A sectional and retrospective study was performed with 20 radicular cysts (RCs) and 20 residual radicular cysts (RRCs) by anti-CD68, anti-CD1a, anti-MMP-9, anti-MMP-13, and anti-TNF-α antibodies. The immunoexpression of MMP-13 and CD68 was significantly higher in RCs when compared to RRCs (P = .011 and P = .012, respectively). An intense inflammatory infiltrate was significantly correlated with CD68 immunoexpression in RCs (P = .025). Macrophages demonstrated a significant positive correlation with MMP-13 (P = .015). A moderate correlation was observed between MMP-9 and MMP-13 (P = .01). TNF-α expression was more common in RCs (P = .001). Langerhans cells were more frequently expressed in atrophic epithelium (P = .041) and significantly correlated with TNF-α (P = .014) in RCs. Macrophages induce a greater release of TNF-α. Higher immunoexpression of MMP-13 and MMP-9 is observed in the early stages of RCs compared to RRCs. The microorganisms are the main factors triggering a proinflammatory immune response and greater cystic expansion in the early stages of these cysts.

Characterization of initial/early histologic features of proliferative leukoplakia and correlation with malignant transformation: a multicenter study

AbstractThe aim of this multicenter retrospective study is to characterize the histopathologic features of initial/early biopsies of proliferative leukoplakia (PL; also known as proliferative verrucous leukoplakia), and to analyze the correlation between histopathologic features and malignant transformation (MT). Patients with a clinical diagnosis of PL who have at least one biopsy and one follow-up visit were included in this study. Initial/early biopsy specimens were reviewed. The biopsies were evaluated for the presence of squamous cell carcinoma (SCCa), oral epithelial dysplasia (OED), and atypical verrucous hyperplasia (AVH). Cases that lacked unequivocal features of dysplasia were termed “hyperkeratosis/parakeratosis not reactive (HkNR)”. Pearson chi-square test and Wilcoxon test were used for statistical analysis. There were 86 early/initial biopsies from 59 patients; 74.6% were females. Most of the cases had a smooth/homogenous (34.8%) or fissured appearance (32.6%), and only 13.0% had a verrucous appearance. The most common biopsy site was the gingiva/alveolar mucosa (40.8%) and buccal mucosa (25.0%). The most common histologic diagnosis was OED (53.5%) followed by HkNR (31.4%). Of note, two-thirds of HkNR cases showed only hyperkeratosis and epithelial atrophy. A lymphocytic band was seen in 34.8% of OED cases and 29.6% of HkNR cases, mostly associated with epithelial atrophy. Twenty-eight patients (47.5%) developed carcinoma and 28.9% of early/initial biopsy sites underwent MT. The mortality rate was 11.9%. Our findings show that one-third of cases of PL do not show OED with most exhibiting hyperkeratosis and epithelial atrophy, but MT nevertheless occurred at such sites in 3.7% of cases.

Beneficial Effects of Intrarosa® (Vaginal Prasterone) on the Vaginal Histology of Women With VVA Treated or not With Aromatase Inhibitors: A Breakthrough in the Understanding of the Role of Androgens in Vaginal Health

ABSTRACT Introduction The vaginal mucosa relies on a constant turnover of its epithelium to remain healthy. Epithelial parabasal cells divide and fill up with glycogen as they get pushed towards the vaginal lumen. They end up desquamating and releasing glycogen for the resident lactobacilli to feed on and acidify the medium. The stimulation required for this quintessential mechanism to go on has historically been attributed to estrogens, however, growing clinical evidence supports that androgens may play a role. Aromatase inhibitors (AI) are used in breast cancer survivors to completely inhibit the synthesis of estrogens. Administering a steroid precursor such as prasterone (DHEA) to patients suffering from vulvovaginal atrophy (VVA) and taking AI will therefore only result in local synthesis of androgens, but no estrogens. Objective We set out to compare the histological changes an atrophic vaginal mucosa goes through with prasterone treatment, with and without exclusion of the estrogenic benefits by AI. Methods A Wittner punch was used to collect biopsies both before and after 12 weeks of treatment with 6.5 mg intravaginal prasterone daily (Intrarosa®). Upon collection, samples were formalin fixed and paraffin embedded for further processing. Morphological assessment of the biopsies was conducted using Masson's trichrome staining. Six menopausal women suffering from VVA and meeting the inclusion criteria were recruited, as well as two breast cancer survivors on AI. Results The degree of epithelial atrophy visible at baseline histology for VVA patients was variable, but all six patients had the histological characteristics of a thick, healthy epithelium by the end of the study. At baseline, both patients on aromatase inhibitors had a very thin, flattened epithelium. Following treatment with prasterone and despite the aromatase inhibitors, the epithelium showed striking histological improvements, regaining thickness, ridges and glycogen synthesis. Conclusions Although there is some level of clinical evidence in the literature suggesting that androgens can help treat symptoms of the genitourinary syndrome of menopause (GSM), data presented here are believed to be the first demonstration of profound beneficial effects of androgens on VVA, independently from estrogens. While further studies are warranted to better understand the respective contributions of androgens and estrogens to the benefits observed with prasterone in the treatment of GSM, the data presented here strongly suggests that androgens play a significant role in the physiopathology of VVA. Disclosure Yes, this is sponsored by industry/sponsor: Endoceutics