Oral Probenecid for Nonhospitalized Adults with Symptomatic Mild-to-Moderate COVID-19.

Probenecid is an orally bioavailable, uricosuric agent that was first approved in 1951 for the treatment of gout, but was later found to have potent, broad-spectrum antiviral activity against several respiratory viruses including SARS-CoV-2. We conducted a phase 2 randomized, placebo-controlled, single-blind, dose-range finding study in non-hospitalized patients with symptomatic, mild-to-moderate COVID-19. Patients were randomly assigned in a 1:1:1 ratio to receive either 500 mg of probenecid, 1000 mg of probenecid, or a matching placebo every 12 h for five days. The patients' COVID-19 viral load hospitalization, or death from any cause through day 28, as well as safety, were evaluated. COVID-19-related symptoms were assessed at baseline, and on days 3, 5, 10, 15, and 28. The primary endpoints of the study were time to first negative SARS-CoV-2 viral test (or viral clearance) and the proportion of patients that were symptom-free at day 5. A total of 75 patients were randomized, with 25 patients in each group. All of the patients completed the study as planned with no hospitalizations or deaths being reported. The median time to viral clearance was significantly shorter for the probenecid 1000 mg group than for placebo (7 days vs. 11 days, respectively; p < 0.0001), and for the probenecid 500 mg group versus placebo (9 days vs. 11 days, respectively; p < 0.0001). In addition, the median time to viral clearance was significantly shorter for the probenecid 1000 mg group than for the probenecid 500 mg group (7 days vs. 9 days, respectively; p < 0.0001). All patients reported at least one COVID-19-related symptom on days 3 and 5; however, on day 10, a significantly greater proportion of patients receiving probenecid 1000 mg reported the complete resolution of symptoms versus placebo (68% vs. 20%, respectively; p = 0.0006), as well as for those receiving probenecid 500 mg versus placebo (56% vs. 20%, respectively, p = 0.0087). The incidence of adverse events during treatment was similar across all groups for any adverse event, and was 12%. All events were mild with no serious adverse events reported and no discontinuations due to an adverse event. The treatment of patients with symptomatic, mild-to-moderate COVID-19 with probenecid resulted in a significant, dose-dependent decrease in the time to viral clearance and a significantly higher proportion of patients reporting complete symptom resolution by day 10. (Supported by TrippBio; ClinicalTrials.gov number, NCT05442983 and Clinical Trials Registry India number CTRI/2022/07/043726).

Immunohistochemical evaluation of p63 and cyclin D1 in oral squamous cell carcinoma and leukoplakia.

OBJECTIVES: There are only a limited number of studies on cyclin D1 and p63 expression in oral squamous cell carcinoma (OSCC) and leukoplakia. This study compared cyclin D1 and p63 expression in leukoplakia and OSCC to investigate the possible correlation of both markers with grade of dysplasia and histological grade of OSCC. MATERIALS AND METHODS: The study included a total of 60 cases, of which 30 were diagnosed with OSCC and 30 with leukoplakia, that were evaluated immunohistochemically for p63 and cyclin D1 expression. Protein expression was correlated based on grades of dysplasia and OSCC. RESULTS: Out of 30 cases of OSCC, 23 cases (76.7%) were cyclin D1 positive and 30 cases (100%) were p63 positive. Out of 30 cases of leukoplakia, 21 cases (70.0%) were cyclin D1 positive and 30 (100%) were p63 positive (P<0.05). CONCLUSION: The overall expression of cyclin D1 and p63 correlated with tumor differentiation, and increases were correlated with poor histological grades, from well-differentiated to poorly-differentiated SCC. Increased cyclin D1 and p63 expression was associated with the severity of leukoplakia. Based on these results cyclin D1 and p63 products can be a useful tool for improved leukoplakia prognosis.

Immunohistochemical study of p21 and Bcl-2 in leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma.

BACKGROUND: Oral Squamous cell carcinoma (OSCC) results from genetic damage, leading to uncontrolled cell proliferation of damaged cells and the cell death. In the course of its progression, visible changes are taking place at the cellular level (atypical) and the resultant at the tissue level (epithelial dysplasia). OBJECTIVES: The Aim of the present study was to evaluate and compare the expressions of intensity of p21 and Bcl-2 in Leukoplakia, oralsubmucous fibrosis (OSMF) and oral squamous cell carcinoma. METHODS: Total 60 cases, 30 cases of oral squamous cell carcinoma, 15 cases of oral submucous fibrosis and 15 cases of Leukoplakia were evaluated immunohistochemically for p21 and Bcl-2 expression. RESULTS: p21 showed positive expression in 13 (86.67%) cases out of 15 cases of OSMF, 12 (80%) cases of leukoplakia out of 15 cases and 24 (80%) cases out of 30 cases of OSCC. The Bcl-2 expression was positive in 13 (86.67%) cases of OSMF, all cases of Leukoplakia and 25 (83.33%) cases of OSCC. No statistical significance was noted in the expression of p21 and Bcl-2 positive expression between OSMF, Leukoplakia and OSCC. Statistical analysis for comparison of intensity of p21 expression in different grades of OSCC showed no significance. Statistical significance difference was found between the expressions of Bcl-2 in moderately and poorly differentiated SCC. CONCLUSION: The intensity of p21 and Bcl-2 expressions in different grades of OSCC indicates a key role in progression of oral neoplasia.

Analysis of gingival biopsies in the Gujarati population: a retrospective study.

BACKGROUND: Biopsy is an important diagnostic tool used in the diagnosis of lesions ranging from simple non-neoplastic, tumor-like lesions to malignancies, and is often the only way to diagnose oral lesions and diseases. The gingiva is the most common site for some kind of irritation or low-grade injury, resulting in localized overgrowths that are considered to be reactive and non-neoplastic lesions. This aim of this study is to analyze the frequency and distribution of gingival lesions in the Gujarati population. MATERIALS AND METHODS: In this retrospective study, gingival biopsies submitted for a period of five years were included. Microscopic slides of all the cases were reviewed by two observers for confirmation of the diagnosis. RESULTS: Among the 106 cases of gingival biopsies, the most frequent category of lesions encountered was the non-neoplastic category, which accounted for 73.58% of the cases. Both benign and malignant neoplasms constituted 26.42% of the cases. Among the non-neoplastic lesions, Pyogenic granuloma was the most frequent lesion (38.46%), followed by fibrous hyperplasia (20.51%), inflammatory hyperplasia (19.23%), and Epulis (8.97%). Neoplasms accounted for 26.42% of the gingival biopsies (92.85% benign and 7.15% malignant). Among the benign neoplastic lesions, Fibroma (30.76%) and Fibrolipoma (26.92%) were the most frequent, followed by peripheral ossifying fibroma (23.08%) and peripheral giant cell granuloma (11%). CONCLUSION: It is difficult to compare studies carried out in various countries due to differences in people's attitudes toward oral health and the accessibility of various population groups to biopsy services. Nevertheless, this study has provided some information about the frequency and distribution of biopsied gingival lesions in the Gujarati population over a period of five years.

Peripheral osteoma of the body of mandible.

Osteoma is a benign osteogenic neoplasm microscopically consisting of proliferation of cancellous or compact bone. Peripheral osteomas (PO) arise from the periosteum and are quite uncommon in the jaw bones. POs of mandible are considered as rare entity and very few cases have been reported in the literature. The pathogenesis of PO is unclear. Some investigators consider it a true neoplasm, while others believe it as a developmental anomaly, a reactive mechanism due to trauma or infection. The purpose of this article is to present the clinical, radiographic, surgical and histological features of a solitary peripheral osteoma of the mandible in a 43-year-old woman and to review the literature for PO located in the mandible.

Mucormycosis of the hard palate masquerading as carcinoma.

A growing number of medically compromised patients are encountered by dentists in their practices. Opportunistic fungal infections such as mucormycosis usually occur in immunocompromised patients but can infect healthy individuals as well. Mucormycosis is an acute opportunistic, uncommon, frequently fatal fungal infection, caused by a saprophytic fungus that belongs to the class of phycomycetes. Among the clinical differential diagnosis we can consider squamous cell carcinoma. Such cases present as chronic ulcers with raised margins causing exposure of underlying bone. There is a close histopathological resemblance between mucormycosis and aspergillosis. Microscopically, aspergillosis has septate branching hyphae, which can be distinguished from mucormycotic hyphae by a smaller width and prominent acute angulations of branching hyphae. A definitive diagnosis of mucormycosis can be made by tissue biopsy that identifies the characteristic hyphae, by positive culture or both. The culture of diseased tissue may be negative and histopathologic examination is essential for early diagnosis. Mucormycosis was long regarded as a fatal infection with poor prognosis. However with early medical and surgical management survival rates are now thought to exceed 80%. In the present case, the fungus was identified by hematoxylin and eosin stain and confirmed by Grocott's silver methenamine special staining technique. Removal of the necrotic bone, which acted as a nidus of infection, was done. Post-operatively patient was advised an obturator to prevent oronasal regurgitation. Since mucormycosis occurs infrequently, it may pose a diagnostic and therapeutic dilemma for those who are not familiar with its clinical presentation.