Cellular senescence implication in mustard keratopathy.

Mustard agents are vesicants that were used in warfare multiple times. They are potent alkylating agents that activate cellular pathways of apoptosis, increase oxidative stress, and induce inflammation. Eyes are particularly susceptible to mustard exposure with a wide range of ocular surface damage. Three main categories of mustard-related eye injuries are acute, chronic, and delayed-onset manifestations. Mustard keratopathy (MK) is a known complication characterized by corneal opacification, ulceration, thinning, and neovascularization that can lead to severe vision loss and discomfort. Recently, a few reports demonstrated the role of senescence induction as a new pathological mechanism in mustard-related injuries that could affect wound healing. We ran the first murine model of delayed-onset MK and nitrogen mustard-induced senescence, evaluating the pathological signs of senescence in the cornea using beta-galactosidase staining. Our results suggest that nitrogen mustard exposure causes senescence in the corneal cells, which could be the underlying mechanism for chronic and late-onset ocular surface damage. We also found a significant correlation between the percentage of positive beta-galactosidase staining and the degree of fibrosis in the cornea. This provides valuable insight into the possible role of anti-senescence drugs in the near future for accelerating corneal healing and restricting fibrosis in patients with mustard keratopathy.

Extracellular-Vesicle-Based Therapeutics in Neuro-Ophthalmic Disorders.

Extracellular vesicles (EVs) have been recognized as promising candidates for developing novel therapeutics for a wide range of pathologies, including ocular disorders, due to their ability to deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, to recipient cells. Recent studies have shown that EVs derived from various cell types, including mesenchymal stromal cells (MSCs), retinal pigment epithelium cells, and endothelial cells, have therapeutic potential in ocular disorders, such as corneal injury and diabetic retinopathy. EVs exert their effects through various mechanisms, including promoting cell survival, reducing inflammation, and inducing tissue regeneration. Furthermore, EVs have shown promise in promoting nerve regeneration in ocular diseases. In particular, EVs derived from MSCs have been demonstrated to promote axonal regeneration and functional recovery in various animal models of optic nerve injury and glaucoma. EVs contain various neurotrophic factors and cytokines that can enhance neuronal survival and regeneration, promote angiogenesis, and modulate inflammation in the retina and optic nerve. Additionally, in experimental models, the application of EVs as a delivery platform for therapeutic molecules has revealed great promise in the treatment of ocular disorders. However, the clinical translation of EV-based therapies faces several challenges, and further preclinical and clinical studies are needed to fully explore the therapeutic potential of EVs in ocular disorders and to address the challenges for their successful clinical translation. In this review, we will provide an overview of different types of EVs and their cargo, as well as the techniques used for their isolation and characterization. We will then review the preclinical and clinical studies that have explored the role of EVs in the treatment of ocular disorders, highlighting their therapeutic potential and the challenges that need to be addressed for their clinical translation. Finally, we will discuss the future directions of EV-based therapeutics in ocular disorders. Overall, this review aims to provide a comprehensive overview of the current state of the art of EV-based therapeutics in ophthalmic disorders, with a focus on their potential for nerve regeneration in ocular diseases.

Regulatory and effector T cell subsets in tumor-draining lymph nodes of patients with squamous cell carcinoma of head and neck.

BACKGROUND: A crucial role for the immune system has been proposed in the establishment and progression of head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the cytokine and regulatory profiles of T cells in tumor draining lymph nodes (TDLNs) of patients with HNSCC. RESULTS: The frequencies of CD4+TNF-α+ and CD4+TNF-αhi negatively were associated with poor prognostic factors such as LN involvement (P = 0.015 and P = 0.019, respectively), stage of the disease (P = 0.032 and P = 0.010, respectively) and tumor size (P = 0.026 and P = 0.032, respectively). Frequencies of CD8+IFN-γ+ and CD8+IFN-γ+ TNF-α+ T cells showed negative relationship with tumor grade (P = 0.035 and P = 0.043, respectively). While, the frequencies of CD4+IL-4+, CD8+IL-10+, CD8+IL-4+T cells were higher in advanced stages of the disease (P = 0.042, P = 0.041 and P = 0.030, respectively) and CD4+IFN-γ+TNF-α-, CD8+IL-4+ and CD8+IFN-γ+TNF-α- T cells were higher in patients with larger tumor size (P = 0.026 and P = 0.032, respectively). Negative associations were found between the frequencies of CD4+CD25+Foxp3+ and CD4+CD25+Foxp3+CD127low/- Treg cells and cancer stage (P = 0.015 and P = 0.059). CONCLUSION: This study shed more lights on the changes in immune profile of T cells in TDLNs of HNSCC. Larger tumor size and/or LN involvement were associated with lower frequencies of CD4+TNF-α+, CD8+IFN-γ+ and CD8+IFN-γ+TNF-α+ but higher frequency of CD4+IL-4+ T cells. Moreover, Foxp3+Tregs correlated with good prognostic indicators.

Accompanying a semi-nested PCR assay to support histopathology findings of fungal keratitis in formalin-fixed paraffin-embedded corneal samples.

BACKGROUND: Fungal species are responsible for 40%-50% of all microbial keratitis cases. Due to the low amount of extracted DNA in ocular Formalin-fixed Paraffin-embedded (FFPE) samples, selecting a reliable molecular method is a substantial issue in this field. METHODS: Sixty-six samples were collected via the penetrating keratoplasty (PK) technique. Histopathology assays were performed using hematoxylin-eosin (H&E) and periodic acid Schiff (PAS) staining methods. The ITS1/ITS4 and ITS1/ITS2 primer pairs were used in a semi-nested polymerase chain reaction (PCR) to target the universal internal transcribed spacer (ITS) region. Some PCR results were validated through sequencing. RESULTS: Fungal DNA was detected in 44 of 66 samples (66.7%), and histopathology was positive for 41 of 66 samples (62.1%). Of 41 histopathologically proven fungal-positive cases, 39 were PCR-positive (95%). Moreover, of 44 PCR-positive samples, 39 (88.6%) were histopathology-positive, and 5 (11.3%) were histopathology-negative. Totally in 39 cases (59%), both histopathology and PCR yielded positive results. The Kappa agreement rate between the two diagnostic methods, including histopathology and PCR, was 0.77. Sensitivity, specificity, positive predictive value, and false predictive value were reported as 88.64%, 90.9%, 95.12%, and 80%, respectively. CONCLUSION: As we reached the acceptable Kappa agreement rate, we concluded that applying the semi-nested PCR assay is a promising method for supporting the evidence by histopathology. Finally, we suggest targeting more specific gene regions using primer pairs that amplify smaller amplicon sizes and surveying novel molecular methods such as NGS to achieve higher sensitivity and Kappa agreement rates.

Evaluating a semi-nested PCR to support histopathology reports of fungal rhinosinusitis in formalin-fixed paraffin-embedded tissue samples.

BACKGROUND: Fungal rhinosinusitis (FRS) encompasses a various spectrum of diseases. Histopathology is the "reference method" for diagnosing FRS, but it cannot determine the genus and species. Moreover, in more than 50% of the histopathologically proven cases, the culture elicited no reliable results. This study was an attempt to evaluate the diagnostic efficiency of semi-nested polymerase chain reaction (PCR) from formalin-fixed paraffin-embedded (FFPE) functional endoscopic sinus surgery (FESS) in FRS patients. METHODS: One hundred ten specimens were subjected to DNA extraction and histopathology examination. The amplification of the ß-globin gene by conventional PCR was used to confirm the quality of extracted DNA. The semi-nested PCR was performed using ITS1, ITS2, and ITS4 primers during two steps. Sequencing the internal transcribed spacer region (ITS1-5.8S-ITS2) to identify causative agents was performed on PCR products. RESULTS: Sixty-four out of 110 samples were positive by histopathology evidence, of which 56 samples (87.5%) were positive by PCR. Out of 46 negative samples by histopathological methods, five samples (10.9%) yielded positive results by PCR. Sensitivity, specificity, positive predictive value, and negative predictive value of the semi-nested PCR method were reported 87.5%, 89.2%, 92.7%, and 85.2%, respectively. The kappa factor between PCR and histopathological methods was 0.76, indicating substantial agreements between these two tests. CONCLUSION: Due to the acceptable sensitivity and specificity of the present method, it might be used to diagnose fungal sinusitis infections along with microscopic techniques. This method is recommended to confirm the diagnose of suspected fungal sinusitis with negative histopathology results.

Orbital mucormycosis in immunocompetent children; review of risk factors, diagnosis, and treatment approach.

BACKGROUND: Orbital mucormycosis is a rare but potentially severe and troublesome invasive fungal infection that could be occurred even in healthy individuals. The initial clinical presentation is similar to bacterial pre-septal or septal cellulitis, especially in early stages. CASE PRESENTATION: Herein, we describe the successful management of a series of five cases presenting with orbital mucormycosis in previously healthy children. CONCLUSIONS: Orbital mucormycosis is extremely rare in healthy children and maybe life-threatening when diagnosis delayed given a similar clinical presentation with bacterial septal cellulitis. Intravenous antifungal therapy with amphotericin B and timely surgical drainage is live-saving.

Papillary Carcinoma of Thyroid with Nasal Cavity Metastases: A Case Report.

Papillary thyroid carcinoma (PTC) is one of the most commonly diagnosed types of differentiated carcinoma of the thyroid. It is stated that lung is the most common site of metastasis followed by bone. The incidence of paranasal sinus (PNS) metastasis is fairly uncommon in case of thyroid carcinoma. To the best of our knowledge, no case of metastatic PTC to nasal cavity has been reported. In this case report, we present the first case of papillary carcinoma of the thyroid with nasal cavity metastases in a 55-year-old female. The patient underwent surgical treatment and the mass was completely removed and sent for pathology. The pathology report revealed that it was metastatic papillary cell carcinoma. Surgical approach is usually difficult in view of the cosmetic and functional concerns, but may be considered in selected cases. As described herein, this rare type of metastasis was successfully removed and the patient was symptoms free after 1-year follow-up.

Caveolin-1 overexpression in benign and malignant salivary gland tumors.

Caveolin-1, a tyrosine-phosphorylated protein, is supposed to have different regulatory roles as promoter or suppressor in many human cancers. However, no published study concerned its expression in benign and malignant salivary gland tumors. The aim of this study was to evaluate and compare the expression of Cav-1 in the most common benign and malignant salivary gland tumors and evaluate its correlation with proliferation activity. In this cross-sectional retrospective study, immunohistochemical expression of caveolin-1 and Ki67 were evaluated in 49 samples, including 11 normal salivary glands, 15 cases of pleomorphic adenoma (PA), 13 adenoid cystic carcinomas (AdCC), and 10 mucoepidermoid carcinomas (MEC). The expression of Cav-1 was seen in 18 % of normal salivary glands and 85 % of tumors. The immunoreaction in the tumors was significantly higher than normal tissues (P = 0.001), but the difference between benign and malignant tumors was not significant (P = 0.07). Expression of Cav-1 was correlated with Ki67 labeling index in PAs, but not in malignant tumors. Cav-1 expression was not in association with tumor size and stage. Overexpression of Cav-1 was found in salivary gland tumors in comparison with normal tissues, but no significant difference was observed between benign and malignant tumors. Cav-1 was inversely correlated with proliferation in PA. Therefore, this marker may participate in tumorigenesis of salivary gland tumors and may be a potential biomarker for cancer treatments.

Clinical implication of CD166 expression in salivary gland tumor.

CD166 is a glycoprotein of immunoglobulin superfamily of adhesion molecules which is overexpressed in many tumors. However, no published literature was found concerning CD166 expression in salivary gland tumor. The purpose of this study was to examine the CD166 expression in the salivary gland tumor by an immunohistochemical approach, to examine the clinical implication of this marker in the prognosis and diagnosis of the salivary gland tumor. In this study, 45 samples of salivary tumors from Khalili Hospital archive including 15 cases of pleomorphic adenoma, 16 cases of mucoepidermoid carcinoma, 14 cases of adenoid cystic carcinoma, and 15 normal salivary glands were selected for immunohistochemistry (IHC) method staining for CD166. CD166 immunoreactivity in malignant tumors (adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC)) (56.7 ± 14.05) was significantly higher than that of pleomorphic adenoma (PA) (34.3 ± 17.07) (P < 0.000) and higher in the PA than normal salivary gland (13.2 ± 12.1) (P = 0.001). CD166 expression was significantly higher in the high-grade tumors (90.3 ± 11.07) compared to low-grade (65.11 ± 27.08) malignant tumors (P = 0.002). CD166 expression showed a significant association with tumor size and the clinical stage (P < 0.001). In conclusion, an overexpression of CD166 was detected in the benign and malignant salivary gland tumors and its expression in the malignant tumor was associated with the aggressive behavior and tumor progression. For this reason, CD166 may be one of the potential biomarkers for predicting tumor behavior in the prognosis of this disease.

Fine-needle aspiration cytological diagnosis of neck masses.

BACKGROUND: Fine-needle aspiration (FNA) is a simple, safe, inexpensive, and acceptable method for diagnosing masses, especially at superficial areas. Therefore, we decided to evaluate the accuracy of FNA cytological diagnosis in nonthyroidal, nonsalivary gland neck masses and compare the results with histopathological diagnosis. MATERIALS AND METHODS: In this retrospective study, all cases with FNA cytological diagnosis of nonthyroidal, nonsalivary gland neck masses from April 2009 to July 2013 were retrieved. The procedure was done by pathologists, and all cytological and histopathological slides of the existing 46 cases were reviewed by 3 pathologists. The values of sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated. RESULTS: SN, SP, PPV, NPV, and accuracy in this study were 79, 100, 100, 73, and 86%, respectively. We had 6 false-negative and no false-positive cases. CONCLUSION: The FNA procedure is a reliable method as the first step for the diagnosis of nonthyroidal, nonsalivary gland neck masses. To increase the diagnostic value of cytology, careful examination of all cytological slides, repetition of the FNA procedure and good history taking are helpful.

Mustard Gas-Induced Ocular Surface Disorders: An Update on the Pathogenesis, Clinical Manifestations, and Management.

PURPOSE: Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to MG. This review provides an update on the pathophysiology, ocular surface complications, and treatment options for MG-related ocular injuries. METHODS: Required information was obtained by reviewing various databases such as Cochrane Library, Google Scholar, and PubMed until March 2022. Data were collected by using keywords: "mustard gas" OR "sulfur mustard" AND "eye" OR "cornea" OR "ocular complication" OR "keratitis" OR "keratopathy" OR "limbal stem cell deficiency" OR "dry eye." RESULTS: Chronic intracellular toxicity, inflammation, and ischemia have been shown to play an essential role in the pathogenesis of MG injury. Ocular surface injuries can have acute, chronic, and most distinctly a delayed-onset presentation leading to various degrees of limbal stem cell deficiency. To date, no treatment has been agreed on as the standard treatment for chronic/delayed-onset MG keratopathy. Based on the authors' experience, we propose a management algorithm for MG-related ocular surface injuries involving optimization of ocular health, anti-inflammatory therapy, and if needed surgical interventions. The management of chronic and delayed-onset presentation remains challenging. CONCLUSIONS: MG keratopathy is a unique form of chemical injury which can lead to a range of ocular surface pathologies. Long-term anti-inflammatory therapy even in patients with seemingly mild disease may potentially reduce the likelihood of the development of more severe delayed-onset disease.

The Potential of Mesenchymal Stem/Stromal Cell Therapy in Mustard Keratopathy: Discovering New Roads to Combat Cellular Senescence.

Mesenchymal stem/stromal cells (MSCs) are considered a valuable option to treat ocular surface disorders such as mustard keratopathy (MK). MK often leads to vision impairment due to corneal opacification and neovascularization and cellular senescence seems to have a role in its pathophysiology. Herein, we utilized intrastromal MSC injections to treat MK. Thirty-two mice were divided into four groups based on the exposure to 20 mM or 40 mM concentrations of mustard and receiving the treatment or not. Mice were clinically and histopathologically examined. Histopathological evaluations were completed after the euthanasia of mice after four months and included hematoxylin and eosin (H&E), CK12, and beta-galactosidase (ß-gal) staining. The treatment group demonstrated reduced opacity compared to the control group. While corneal neovascularization did not display significant variations between the groups, the control group did register higher numerical values. Histopathologically, reduced CK12 staining was detected in the control group. Additionally, ß-gal staining areas were notably lower in the treatment group. Although the treated groups showed lower severity of fibrosis compared to the control groups, statistical difference was not significant. In conclusion, it seems that delivery of MSCs in MK has exhibited promising therapeutic results, notably in reducing corneal opacity. Furthermore, the significant reduction in the ß-galactosidase staining area may point towards the promising anti-senescence potential of MSCs.

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in the Human Eye.

PURPOSE: To determine the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in postmortem ocular specimens of patients with severe COVID-19 disease. PATIENTS AND METHODS: Postmortem conjunctival (28 samples), aqueous humor (30 samples) and vitreous humor (30 samples) specimens were obtained bilaterally from the eyes of 15 deceased COVID-19 patients within one hour of death. The presence of viral RNA was evaluated in samples using Real-time reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Positive RT-PCR SARS-COV-2 results were found in one conjunctival and 2 vitreous humor samples. All aqueous humor samples tested negative for the presence of SARS-COV-2 RNA. Of note, three positive samples were obtained from three different patients. The overall prevalence of positive RT-PCR ocular samples was 3.4% among all samples and 20% at the patient level. CONCLUSION: SARS-CoV-2 RNA is detectable in postmortem conjunctival and vitreous humor samples of patients with severe COVID-19.

Intrastromal versus subconjunctival injection of mesenchymal stem/stromal cells for promoting corneal repair.

PURPOSE: Different approaches to delivery of mesenchymal stem/stromal cells (MSCs) for ameliorating corneal injuries have been investigated. This study was aimed to compare the efficacy of intrastromal and subconjunctival injection of human bone marrow-derived MSCs (hBM-MSCs) in a corneal epithelial injury model. METHODS: Twenty-four C57BL/6J mice underwent total corneal and limbal epithelial debridement. Then, the mice were divided into three different groups: (1) intrastromal hBM-MSCs injection, (2) subconjunctival hBM-MSCs injection, and (3) injection of frozen medium as a control. Mice were monitored by slit lamp and underwent anterior segment optical coherence tomography (ASOCT). Following euthanasia, the corneas were further evaluated by histology and immunostaining. RESULTS: hBM-MSC injection successfully healed epithelial defects regardless of the delivery route (P < 0.001). However, intrastromal injection was superior to subconjunctival injection in reducing defect area (P = 0.001). Intrastromal injection of hBM-MSCs also significantly reduced corneal opacity and neovascularization and improved ASOCT parameters compared to subconjunctival injection or no treatment (P < 0.001, P = 0.003, and P < 0.001, respectively). Although both of the treatment groups were positive for CK12 and had reduced levels of MUC5AC compared to the control, CK12 staining was stronger in the intrastromal group compared to the subconjunctival group. Also, persistency of MSCs was confirmed by in vivo (up to 2 weeks) and in vitro assessments (up to 4 weeks). CONCLUSIONS: Although the injection of hBM-MSC using both intrastromal and subconjunctival methods improve wound healing and reduce neovascularization and opacity, the intrastromal approach is superior in terms of corneal healing.

The hospitalization rate and clinical characteristics of mucormycosis prior and during COVID-19 pandemic: A single-center study.

INTRODUCTION: There have been some reports of the association between SARS-CoV-2 infection and mucormycosis. This study aims to compare the hospitalization rates and clinical characteristics of mucormycosis before and during the COVID-19 pandemic. METHODOLOGY: In this retrospective study, we compared the hospitalization rate of mucormycosis patients in Namazi hospital in Southern Iran for two periods of 40 months. We defined July 1st, 2018 to February 17th, 2020, as the pre-COVID-19 period and February 18th, 2020, to September 30th, 2021, as the COVID-19 period. In addition, a quadrupled group of hospitalized patients with age and sex-matched SARS-COV-2 infection without any sign of mucormycosis was selected as the control group for COVID-associated mucormycosis. RESULT: In the total of 72 mucormycosis patients in the COVID period, 54 patients had a clinical history and a positive RT-PCR, which confirms the diagnosis of SARS-COV2 infection. The hospitalization rate of mucormycosis showed an increase of + 306% (95% CI: + 259%, + 353%) from a monthly average value of 0.26 (95% confidence interval (CI): 0.14, 0.38) in the pre-COVID period to 1.06 in the COVID period. The use of corticosteroids prior to the initiation of hospitalization (p ≤ 0.01), diabetes (DM) (p = 0.04), brain involvement (p = 0.03), orbit involvement (p = 0.04), and sphenoid sinus invasion (p ≤ 0.01) were more common in patients with mucormycosis during the COVID period. CONCLUSIONS: In high-risk patients, especially diabetics, special care to avoid the development of mucormycosis must be taken into account in patients with SARS-COV-2 infection considered for treatment with corticosteroids.

A Rare Case of Nodular Lymphocyte Predominance Hodgkin's Lymphoma of the Parotid Gland: Diagnostic Pitfall in Fine Needle Aspiration Cytology.

Primary malignant lymphoma of the salivary glands is a very rare entity, and primary parotid Hodgkin's Lymphoma (HL) is even rarer. It is rare in the initial evaluation to suspect a parotid tumor. Thus, it is important to keep lymphomatous involvement in mind when facing parotid masses in differential diagnosis. This study presented a case of a 56-year-old male with a 5-month history of left cheek enlargement. Fine Needle Aspiration (FNA) biopsy was performed with no suspicion for lymphoma. Parotidectomy was also done and nodular lymphocyte predominance HL within the parotid gland was confirmed by immunohistochemical study. The Nodular Lymphocyte Predominance Hodgkin's Lymphoma has been defined as a specific histopathological subtype of HL. The initial diagnostic approach is usually carried out through FNA, obtaining high sensitivity and specificity, which allows establishing an adjusted for co-correct diagnosis.

Proteomics Study of Mesenchymal Stem Cell-Like Cells Obtained from Tumor Microenvironment of Patients with Malignant and Benign Salivary Gland Tumors.

Objective: Salivary gland tumors (SGTs) show some aggressive and peculiar clinicopathological behaviors that might be related to the components of the tumor microenvironment, especially mesenchymal stem cells (MSCs)-associated proteins. However, the role of MSCs-related proteins in SGTs tumorigenesis is poorly understood. This study aimed to isolate and characterize MSCs from malignant and benign tumor tissues and to identify differentially expressed proteins between these two types of MSCs. Materials and Methods: In this experimental study, MSC-like cells derived from benign (pleomorphic adenoma, n=5) and malignant (mucoepidermoid carcinoma, n=5) tumor tissues were verified by fluorochrome antibodies and flow cytometric analysis. Differentially expressed proteins were identified using two-dimensional polyacrylamide gel electrophoresis (2DE) and Mass spectrometry. Results: Results showed that isolated cells strongly expressed characteristic MSCs markers such as CD44, CD73, CD90, CD105, and CD166, but they did not express or weakly expressed CD14, CD34, CD45 markers. Furthermore, the expression of CD24 and CD133 was absent or near absent in both isolated cells. Results also discovered overexpression of Annexin A4 (Anxa4), elongation factor 1-delta (EF1-D), FK506 binding protein 9 (FKBP9), cytosolic platelet-activating factor acetylhydrolase type IB subunit beta (PAFAH1B), type II transglutaminase (TG2), and s-formylglutathione hydrolase (FGH) in MSCs isolated from the malignant tissues. Additionally, heat shock protein 70 (Hsp70), as well as keratin, type II cytoskeletal 7 (CK-7), were found to be overexpressed in MSCs derived from the benign ones. Conclusion: Malignant and benign SGTs probably exhibit a distinct pattern of tissue proteins that are most likely related to the metabolic pathway. However, further studies in a large number of patients are required to determine the applicability of identified proteins as new targets for cancer therapy.

CD45RO+TILs: cellular biomarkers for larynx squamous cell carcinoma outcome.

OBJECTIVE: The prognostic importance of Tumor-Infiltrating Lymphocytes (TILs) in the tumor microenvironment of various cancers is increasingly recognized. In the present study, we aimed to investigate the prognostic value of CD3+, CD4+, CD8+, and CD45RO + TILs and their relation to histopathological features in larynx squamous cell carcinoma. METHODS: Formalin-Fixed and Paraffin-Embedded (FFPE) samples from 63 primary larynx squamous cell carcinoma patients were immunostained for CD3, CD4, CD8, and CD45RO expression. Positive cells in micrographs from Invasive Margin (IM) and Tumor Center (CT) of tissue specimens counted by ImageJ software and their correlation with disease outcome were analyzed. RESULTS: The expression level of TILs subpopulations was associated with clinicopathological markers as well as Overall Survival (OS) and Disease-Free Survival (DFS). In multivariate analysis, high frequency of CD45RO + cells in IM were confirmed as an independent prognostic marker for DFS (p = 0.007, HR = 4.968) and OS (p = 0.007, HR = 4.957). Similar findings were observed in the multivariate analysis of the combined frequency of CD45RO+cells in IM and CT. CONCLUSION: TILs are associated with patients clinicopathological features. Also, our findings indicate that CD45RO + TILs are a valuable marker for risk prediction in larynx SCC and could predict patients' outcomes.

Sinoorbital Mucormycosis Associated with Corticosteroid Therapy in COVID-19 Infection.

BACKGROUND: Mucormycosis is a rare and invasive fungal infection, affecting almost exclusively immunocompromised individuals. Immunosuppressive effects of corticosteroids which are widely prescribed in COVID-19 patients might be a predisposing factor for opportunistic infections even though the other factors should also be considered. Case Presentation. A middle-aged man without any significant past medical history was admitted to the hospital due to a severe COVID-19 infection. He received a high dose of corticosteroids as a part of the treatment. Five days after discharge, he presents with a headache and fever. Eventually, orbital mucormycosis was diagnosed for him and he was treated with antifungal medications. CONCLUSION: Opportunistic infections should be considered during the current pandemic of COVID-19, during which corticosteroids are widely prescribed.

A comparison of performance of anti-cyclic citrullinated peptide 2 and citrullinated protein antibodies in the diagnosis of rheumatoid arthritis in Iranian patients.

Antibodies to citrullinated proteins and rheumatoid factor (RF) are widely used in patients with rheumatoid arthritis (RA) and the antibodies to citrullinated proteins appear to be the most specific markers of the disease. The objective was to compare the diagnostic performance of the anti-cyclic citrullinated peptide 2 (anti-CCP2) and citrullinated protein Antibodies (CPA) with RF in the diagnosis of RA. Serum samples of 139 patients with RA and 131 patients with other rheumatic diseases were checked for anti-CCP2, CPA uses citrullinated recombinant rat filaggrin as the antigen assay, and RF. The specificity, sensitivity, and receiver operating characteristic (ROC) of tests were then compared. The sensitivity of anti-CCP2, CPA, and RF were 82.7, 83.5, and 61.5%, respectively. The specificities of the tests were 91.2, 78.6, and 90.5%, respectively. The area under ROC curves for the tests were 0.925, 0.890, and 0.847, respectively. Exclusion of overlaps was associated with improved specificity for CPA but no change in the specificity of RF and anti-CCP. The sensitivity of anti-CCP2, CPA, and RF were 66.7, 77.8, and 51.9% for patients with early RA, respectively. The findings of the present study indicate that anti-CCP2 might be of a better diagnostic value for the diagnosis of RA. They also showed that CPA and in the second place anti-CCP2 were useful in the diagnosis of early RA.