Survival analysis over a 20-year period of a Brazilian cohort of blood donors coinfected HIV-HCV

ABSTRACT Among individuals coinfected with HCV and HIV, studies of mortality from non-hepatic causes have shown inconsistent results. The aim of this study was to investigate the contribution of HCV and HIV co-infection to mortality from hepatic and non-hepatic causes in Brazil. This retrospective cohort study included blood donors from Fundação Pró-Sangue de São Paulo (FPS) who were followed from 1994 to 2016 to compare mortality and its causes between HIV-HCV coinfected individuals versus those seronegative for all tested infections. Records from the FPS database and the Mortality Information System were linked through a probabilistic record Relationship (RL). The Hazard Ratio (HR) was estimated using Cox multiple regression models. HCV-HIV coinfected individuals compared to seronegative individuals had a higher risk of death from all causes (HR = 14.54), non-liver neoplasms (HR = 2.55), infections (HR = 10.37) and liver disease (HR = 7.0). In addition, HCV mono-infected individuals compared to seronegative individuals had a higher risk of death from all causes (HR = 2.23), liver cancer (HR = 32.21), liver disease (HR = 14.92), infection (HR = 3.22), and trauma (HR = 1.68). Individuals coinfected with HCV and HIV have increased overall mortality and death due to infections, liver diseases and non-liver neoplasms as compared to those uninfected with HCV and HIV.

Immunoexpression of PD-L1, CD4+ and CD8+ cell infiltrates and tumor-infiltrating lymphocytes (TILs) in the microenvironment of actinic cheilitis and lower lip squamous cell carcinoma.

OBJECTIVE: Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient.Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics. METHODOLOGY: This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry. RESULTS: There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells. CONCLUSION: Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs.

Potential Histopathological and Immune Biomarkers in Malignant and Non-Malignant Oral Lesions.

Objectives: The presented case-control study was developed to characterize the clinical, histopathological and immunological profile of patients with traumatic injuries, benign neoplasms, potentially malignant oral disorders and malignant neoplasms of the oral cavity, in order to identify biomarkers of malignancy. Material and Methods: Clinical information was collected from dental records and several techniques were performed, including histopathological evaluation in sections stained with haematoxylin and eosin, immunohistochemistry for programmed death ligand-1 and measurement of serum levels of interferon-gamma, interleukin-6, -10 and -12. Statistical analysis was performed using IBM SPSS® Statistics software. Results: This study included 8 patients with traumatic injuries, 8 with benign neoplasms, 6 with potentially malignant oral disorders and 11 with malignant neoplasms. An association was observed between the classification of the lesion and smoking (P < 0.05), the size of the lesion (P < 0.05), the density of the inflammatory infiltrate (P < 0.001), the degree of dysplasia (P < 0.01) and programmed death ligand-1 expression (P < 0.01). Conclusions: Therefore, it is suggested that smoking, the size of the lesion, the inflammatory infiltrate and the programmed death ligand-1 expression can be considered potential biomarkers of oral malignancy.

Immunoexpression of PD-L1, CD4+ and CD8+ cell infiltrates and tumor-infiltrating lymphocytes (TILs) in the microenvironment of actinic cheilitis and lower lip squamous cell carcinoma

Abstract Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient. Objective: Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics. Methodology: This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry. Results: There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells. Conclusion: Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs.

ORAL HAIRY POLYP IN A TEENAGER: CASE REPORT AND LITERATURE REVIEW.

OBJECTIVE: To report an unusual case of oral hairy polyp (HP) and review the literature, providing epidemiological, clinical and histopathological information on this disease. CASE DESCRIPTION: A 12-year-old male patient was referred to a Stomatology department with a nodule in the posterior midline of the tongue. The patient did not know exactly when it arose or whether it had grown since then. Clinical exam revealed a bulky and mobile pedunculated mass lesion on the dorsum of the tongue, with a diameter of approximately 1 cm. The patient's mother reported no previous health problem. An excisional biopsy was performed, the surgical specimen was sent for anatomopathological analysis, and the findings were compatible with the diagnosis of HP. COMMENTS: Hairy polyp is a rare lesion, especially in the oral region. The literature search revealed only 10 case reports of oral HP published between January 1999 and January 2019, and they revealed a predominance of the disease in female newborns. Two uncommon facts were presented in this case: the patient was male and diagnosis was made at 12 years old.

Oral hairy polyp in a teenager: case report and literature review / Pólipo piloso oral em um adolescente: relato de caso e revisão de literatura

ABSTRACT Objective: To report an unusual case of oral hairy polyp (HP) and review the literature, providing epidemiological, clinical and histopathological information on this disease. Case description: A 12-year-old male patient was referred to a Stomatology department with a nodule in the posterior midline of the tongue. The patient did not know exactly when it arose or whether it had grown since then. Clinical exam revealed a bulky and mobile pedunculated mass lesion on the dorsum of the tongue, with a diameter of approximately 1 cm. The patient's mother reported no previous health problem. An excisional biopsy was performed, the surgical specimen was sent for anatomopathological analysis, and the findings were compatible with the diagnosis of HP. Comments: Hairy polyp is a rare lesion, especially in the oral region. The literature search revealed only 10 case reports of oral HP published between January 1999 and January 2019, and they revealed a predominance of the disease in female newborns. Two uncommon facts were presented in this case: the patient was male and diagnosis was made at 12 years old.

RESUMO Objetivo: Relatar um caso incomum de pólipo piloso (PP) oral e revisar a literatura para trazer informações epidemiológicas, clínicas e histopatológicas acerca da doença. Descrição do caso: Paciente do sexo masculino, 12 anos de idade, encaminhado ao Departamento de Estomatologia com nódulo na região posterior de linha média da língua. O paciente não soube relatar quando surgiu a lesão e se ela havia crescido desde então. O exame clínico revelou massa pedunculada, volumosa e móvel no dorso da língua, medindo aproximadamente 1,0 cm de diâmetro. A mãe do paciente relatou que ele nunca havia tido nenhum problema de saúde anterior. Foi realizada biópsia excisional e o material foi enviado para análise anatomopatológica, sendo os achados compatíveis com o diagnóstico de PP. Comentários: O pólipo piloso é uma lesão rara, especialmente na região oral. A pesquisa bibliográfica revelou apenas dez relatos de casos de PP oral, publicados entre janeiro de 1999 e janeiro de 2019, sendo observada predominância da doença em recém-nascidos do sexo feminino. Dois fatos incomuns ocorreram neste caso: tratava-se de um paciente do sexo masculino e o diagnóstico se deu aos 12 anos de idade.

Multibacillary leprosy patients with high and persistent serum antibodies to leprosy IDRI diagnostic-1/LID-1: higher susceptibility to develop type 2 reactions

Leprosy inflammatory episodes [type 1 (T1R) and type 2 (T2R) reactions] represent the major cause of irreversible nerve damage. Leprosy serology is known to be influenced by the patient’s bacterial index (BI) with higher positivity in multibacillary patients (MB) and specific multidrug therapy (MDT) reduces antibody production. This study evaluated by ELISA antibody responses to leprosy Infectious Disease Research Institute diagnostic-1 (LID-1) fusion protein and phenolic glycolipid I (PGL-I) in 100 paired serum samples of 50 MB patients collected in the presence/absence of reactions and in nonreactional patients before/after MDT. Patients who presented T2R had a median BI of 3+, while MB patients with T1R and nonreactional patients had median BI of 2.5+ (p > 0.05). Anti-LID-1 and anti-PGL-I antibodies declined in patients diagnosed during T1R (p < 0.05). Anti-LID-1 levels waned in MB with T2R at diagnosis and nonreactional MB patients (p < 0.05). Higher anti-LID-1 levels were seen in patients with T2R at diagnosis (vs. patients with T1R at diagnosis, p = 0.008; vs. nonreactional patients, p = 0.020) and in patients with T2R during MDT (vs. nonreactional MB, p = 0.020). In MB patients, high and persistent anti-LID-1 antibody levels might be a useful tool for clinicians to predict which patients are more susceptible to develop leprosy T2R.

Description of leprosy classification at baseline among patients enrolled at the uniform multidrug therapy clinical trial for leprosy patients in Brazil.

The uniform multidrug therapy clinical trial, Brazil (U-MDT/CT-BR), database was used to describe and report the performance of available tools to classify 830 leprosy patients as paucibacillary (PB) and multibacillary (MB) at baseline. In a modified Ridley and Jopling (R&J) classification, considering clinical features, histopathological results of skin biopsies and the slit-skin smear bacterial load results were used as the gold standard method for classification. Anti-phenolic glycolipid-I (PGL-I) serology by ML Flow test, the slit skin smear bacterial load, and the number of skin lesions were evaluated. Considering the R&J classification system as gold standard, ML Flow tests correctly allocated 70% patients in the PB group and 87% in the MB group. The classification based on counting the number of skin lesions correctly allocated 46% PB patients and 99% MB leprosy cases. Slit skin smears properly classified 91% and 97% of PB and MB patients, respectively. Based on U-MDT/CT-BR results, classification of leprosy patients for treatment purposes is unnecessary because it does not impact clinical and laboratories outcomes. In this context, the identification of new biomarkers to detect patients at a higher risk to develop leprosy reactions or relapse remains an important research challenge.