A Case of Statin-Associated Autoimmune Myopathy: Management and Treatment.

Elevated lipid panels are associated with an increased risk of cardiovascular disease. Management of heart disease with lipid lowering agents play a vital role in medicine. Statins are one group of medications that are widely utilized in the medical field to decrease the risk of atherosclerotic disease. Statins work by inhibiting the hepatic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Although statins are one of the most effective drugs for secondary and primary prevention of heart disease, they are not without risks and side effects such as hepatotoxicity and myopathy. We present a case of a male patient who developed progressively worsening muscle weakness and elevated muscle enzyme markers upon initiation of a statin. His symptoms persisted despite a trial of an alternative statin and subsequent discontinuation of all statin medications. A multitude of possible etiologies were considered and ranged from infectious, autoimmune, cancerous, to congenital in nature. Environmental factors, such as exposure to medications or toxins, were also considered as one of the possible precipitating factors. The association between his statin consumption and muscle weakness were not easily apparent at first. He required further workup including physical examination, electromyography, panel of myositis antibodies, and muscle biopsy. After clinical suspicion and elevated antibodies to HMGCR beyond the normal limit, he was discovered to have statin-associated autoimmune myopathy. The patient improved with the treatment of immunosuppressive agent's prednisone and methotrexate.

Selective Neck Dissection for Node-Positive Oral Cavity Squamous Cell Carcinoma: A Retrospective Cohort Study.

Introduction Selective neck dissection in clinically node-negative neck is considered the standard of care for oral squamous cell carcinomas (SCCs). Controversy still prevails in node-positive disease regarding the extent of neck dissection. In our part of the world, comprehensive neck dissection is mostly considered to be the minimal optimal treatment for palpable neck disease. Objective To compare regional control and disease-specific survival between clinically node-positive and node-negative patients undergoing selective neck dissection for oral SCC. Methods This was a retrospective cohort study conducted in the department of ENT, Head and Neck surgery at a tertiary care hospital. All patients with biopsy-proven oral and lip SCC, with or without nodal disease, who underwent selective neck dissection between April 2006 and July 2015 were included in the study. Results During the study period, 111 patients with oral SCC underwent selective neck dissection, of whom 71 (62%) were clinically node-negative and 40 (38%) patients had clinically positive nodes in the neck. The mean follow-up was 16.62 months (standard deviation [SD]: 17.03). The overall regional control rates were 95 versus 96% for clinical negative versus positive nodes, respectively ( p = 0.589). The disease-specific survival was 84.5% in the node negative group versus 82.5% in the node-positive group ( p = 0.703). Conclusion Selective neck dissection in node-positive neck oral SCC has similar regional control rates when compared with node-negative neck SCC. The difference in disease-specific survival between the two groups is also not significant.

Expression of the BAD pathway is a marker of triple-negative status and poor outcome.

Triple-negative breast cancer (TNBC) has few therapeutic targets, making nonspecific chemotherapy the main treatment. Therapies enhancing cancer cell sensitivity to cytotoxic agents could significantly improve patient outcomes. A BCL2-associated agonist of cell death (BAD) pathway gene expression signature (BPGES) was derived using principal component analysis (PCA) and evaluated for associations with the TNBC phenotype and clinical outcomes. Immunohistochemistry was used to determine the relative expression levels of phospho-BAD isoforms in tumour samples. Cell survival assays evaluated the effects of BAD pathway inhibition on chemo-sensitivity. BPGES score was associated with TNBC status and overall survival (OS) in breast cancer samples of the Moffitt Total Cancer Care dataset and The Cancer Genome Atlas (TCGA). TNBC tumours were enriched for the expression of phospho-BAD isoforms. Further, the BPGES was associated with TNBC status in breast cancer cell lines of the Cancer Cell Line Encyclopedia (CCLE). Targeted inhibition of kinases known to phosphorylate BAD protein resulted in increased sensitivity to platinum agents in TNBC cell lines compared to non-TNBC cell lines. The BAD pathway is associated with triple-negative status and OS. TNBC tumours were enriched for the expression of phosphorylated BAD protein compared to non-TNBC tumours. These findings suggest that the BAD pathway it is an important determinant of TNBC clinical outcomes.

Selective Neck Dissection for Node-Positive Oral Cavity Squamous Cell Carcinoma: A Retrospective Cohort Study

Abstract Introduction Selective neck dissection inclinically node-negative neckisconsidered the standard of care for oral squamous cell carcinomas (SCCs). Controversy still prevailsinnode-positive disease regarding the extent of neck dissection. In our part of the world, comprehensive neck dissection is mostly considered to be the minimal optimal treatment for palpable neck disease. Objective To compare regional control and disease-specific survival between clinically node-positive and node-negative patients undergoing selective neck dissection for oral SCC. Methods This was a retrospective cohort study conducted in the department of ENT, Head and Neck surgery at a tertiary care hospital. All patients with biopsy-proven oral and lip SCC, with or without nodal disease, who underwent selective neck dissection between April 2006 and July 2015 were included in the study. Results During the study period, 111 patients with oral SCC underwent selective neck dissection, of whom 71 (62%) were clinically node-negative and 40 (38%) patients had clinically positive nodes in the neck. The mean follow-up was 16.62 months (standard deviation [SD]: 17.03). The overall regional control rates were 95 versus 96% for clinical negative versus positive nodes, respectively (p = 0.589). The disease-specific survival was 84.5% in the node negative group versus 82.5% in the node-positive group (p = 0.703). Conclusion Selective neck dissection in node-positive neck oral SCC has similar regional control rates when compared with node-negative neck SCC. The difference in disease-specific survival between the two groups is also not significant.

Fluctuations of functionally distinct CD8+ T-cell clonotypes demonstrate flexibility of the HIV-specific TCR repertoire.

T-cell receptor (TCR) diversity of virus-specific CD8+ T cells likely helps prevent escape mutations in chronic viral infections. To understand the dynamics of the virus-specific T cells in more detail, we followed the evolution of the TCR repertoire specific for a dominant HLA-B*08-restricted epitope in Nef (FLKEKGGL) in a cohort of subjects infected with HIV. Epitope-specific CD8+ T cells used structurally diverse TCR repertoires, with different TCRbeta variable regions and with high amino acid diversity within antigen recognition sites. In a longitudinal study, distinct Vbeta populations within the HIV-specific TCR repertoire expanded simultaneously with changes in plasma viremia, whereas other Vbeta populations remained stable or even decreased. Despite antigenic variation in some subjects, all subjects had the consensus sequence present during the study period. Functional analysis of distinct Vbeta populations revealed differences in HIV-specific IFN-gamma secretion ex vivo as well as differences in tetramer binding, indicating functional heterogeneity among these populations. This contrasts with findings in a subject on antiretroviral therapy with suppression of viremia to less than 50 copies/mL, where we observed long-term persistence of a single clonotype. Our findings illustrate the flexibility of a heterogeneous HIV-1-specific CD8+ TCR repertoire in subjects with partial control of viremia.