RESUMO
ABSTRACT: Lichen sclerosus (LS) is a frequently encountered inflammatory skin disorder characterized by whitened, atrophic patches that can cause pain and pruritus. The underlying cause of this condition remains unknown. Primarily affecting the genital area, this condition carries an increased risk of developing cutaneous cancers and frequently co-occurs with autoimmune disorders. Our retrospective study aimed to explore histologic features of LS, with a particular focus on a newly established finding and its potential implications. We examined 53 histologic cases of LS collected over 2 years. Experienced pathologists evaluated and reached a consensus on the assignment of histologic features. Patient charts were manually reviewed to gather relevant demographic and clinical data. Statistical analysis was performed using IBM SPSS Statistics (2021). Of the 53 total patients identified as meeting criteria for inclusion in this study, only 8 (15%) were male. Eight cases (15%) demonstrated perineural inflammatory infiltrate. Notably, half of all samples from male patients exhibited perineural inflammatory infiltrate. A statistically significant increase ( P < 0.01) in the presence of dermal plasma cells was identified in cases with perineural inflammation versus cases without this feature. The findings of our study highlight the recurrent nature of perineural inflammation in LS, providing valuable insights into this condition. Furthermore, we observed a notable correlation between perineural inflammation, male patients, and the presence of dermal plasma cells. These discoveries contribute to a better understanding of the underlying mechanisms of LS and suggest avenues for future research into the condition.
Assuntos
Doenças Autoimunes , Líquen Escleroso e Atrófico , Humanos , Masculino , Feminino , Líquen Escleroso e Atrófico/complicações , Líquen Escleroso e Atrófico/patologia , Estudos Retrospectivos , Inflamação , PruridoRESUMO
BACKGROUND: Although uncommon, pneumothorax is a potentially serious complication following open reduction and internal fixation (ORIF) of clavicle fractures. In many centres it is routine practice to obtain postoperative chest radiographs following ORIF of clavicle fractures to assess for iatrogenic pneumothorax. Given the need to contain health care costs, the low sensitivity for detecting small pneumothorax and a desire to decrease patient radiation exposure, the practice of ordering chest radiographs following ORIF of clavicle fractures may be unnecessary. METHODS: All patients undergoing ORIF of clavicle fractures with plate and screw fixation at Kingston Health Sciences Centre between April 2009 and June 2020 were identified from the Discharge Abstract Database (inpatient) and National Ambulatory Care Reporting System (outpatient) using relevant Canadian Classification of Health Intervention procedure codes. Charts were manually reviewed to confirm diagnosis and procedure, and patients with preoperative pneumothorax were excluded. The frequency of postoperative chest radiograph and pneumothorax detection were calculated. RESULTS: Among the 292 patients who underwent ORIF of clavicle fractures during the study period, 17 were excluded for having a pneumothorax on preoperative chest radiograph. Of the remaining 275 patients, 101 (36.7%) had postoperative chest radiographs, of whom none were found to have postoperative iatrogenic pneumothorax. CONCLUSION: Since 2009, the rate of routine postoperative chest radiography following ORIF of clavicle fractures is 36.7% at our centre. During this time period, none of the 101 patients who had postoperative chest radiographs had a postoperative iatrogenic pneumothorax. To our knowledge, this is the largest series of patients available, and our findings confirm those of several smaller studies. Owing to the low rate of postoperative iatrogenic pneumothorax, we conclude that postoperative chest radiography is unnecessary following ORIF of clavicle fractures.
Assuntos
Fraturas Ósseas , Pneumotórax , Humanos , Clavícula/diagnóstico por imagem , Clavícula/cirurgia , Pneumotórax/diagnóstico por imagem , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Estudos Retrospectivos , Canadá , Pacientes Ambulatoriais , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgiaRESUMO
Efficacy of oncolytic, conditionally-replicating adenovirus (CRAd) vectors can be enhanced by "arming" the vector with therapeutic transgenes. We examined whether inclusion of an intact early region 3 (E3) and the reptilian reovirus fusogenic p14 fusion-associated small transmembrane (FAST) protein enhanced vector efficacy. The p14 FAST transgene was cloned between the fiber gene and E4 region, with an upstream splice acceptor for replication-dependent expression from the major late promoter. In A549 cells, this vector expressed p14 FAST protein at very low levels, and showed a poor ability to mediate cell-cell fusion, relative to a similar vector encoding p14 FAST within the E3 deletion. Although expression of E3 proteins from the CRAd increased plaque size, poor expression of p14 FAST protein compromised the fusogenic capacity of the vector. Thus, location of a therapeutic transgene within a CRAd can significantly impact expression of the transgene and is an important consideration in vector design.
Assuntos
Proteínas E3 de Adenovirus/genética , Adenovírus Humanos/genética , Vetores Genéticos , Vírus Oncolíticos/genética , Transgenes , Proteínas Virais de Fusão/genética , Células A549 , Proteínas E3 de Adenovirus/metabolismo , Adenovírus Humanos/fisiologia , Expressão Gênica , Genoma Viral , Células HEK293 , Humanos , Vírus Oncolíticos/fisiologia , Splicing de RNA , Proteínas Virais de Fusão/metabolismoAssuntos
COVID-19/epidemiologia , Internato e Residência/estatística & dados numéricos , Entrevistas como Assunto/estatística & dados numéricos , Candidatura a Emprego , Ortopedia/estatística & dados numéricos , Pandemias , Canadá/epidemiologia , Estágio Clínico/organização & administração , Estágio Clínico/estatística & dados numéricos , Humanos , Internato e Residência/organização & administração , Ortopedia/educação , Ortopedia/organização & administraçãoRESUMO
Oncolytic viruses are designed to replicate in and kill cancer cells, and have shown tremendous promise in preclinical and clinical studies. Indeed, several oncolytic viruses are available to patients in a number of different countries around the world. However, most oncolytic viruses show a poor ability to spread throughout the tumor mass, frequently leading to only a partial response and regrowth of the tumor. One approach to improve spread of the viral effect throughout the tumor mass is to arm the oncolytic virus with a fusogenic protein. In this manner, a single infected cell can fuse with many adjacent uninfected cells, essentially amplifying the anti-tumor effects. In this review, we discuss the development and use of fusogenic proteins to enhance the efficacy of human adenovirus-based vectors for cancer therapy.
Assuntos
Adenoviridae/efeitos dos fármacos , Fusão Celular/métodos , Neoplasias/tratamento farmacológico , Terapia Viral Oncolítica/métodos , HumanosRESUMO
Cancer is a devastating disease that affects millions of patients every year, and causes an enormous economic burden on the health care system and emotional burden on affected families. The first line of defense against solid tumors is usually extraction of the tumor, when possible, by surgical methods. In cases where solid tumors can not be safely removed, chemotherapy is often the first line of treatment. As metastatic cancers often become vigorously resistant to treatments, the development of novel, more potent and selective anti-cancer strategies is of great importance. Adenovirus (Ad) is the most commonly used virus in cancer clinical trials, however, regardless of the nature of the Ad-based therapeutic, complete responses to treatment remain rare. A number of pre-clinical studies have shown that, for all vector systems, viral spread throughout the tumor mass can be a major limiting factor for complete tumor elimination. By expressing exogenous cell-fusion proteins, many groups have shown improved spread of Ad-based vectors. This review summarizes the research done to examine the potency of Ad vectors expressing fusogenic proteins as anti-cancer therapeutics.