Blood Epstein–Barr virus DNA does not predict outcome in advanced HIV-associated Hodgkin lymphoma

In HIV-seronegative patients with advanced Hodgkin lymphoma (HL), Epstein–Barr virus (EBV) viraemia at diagnosis predicts a worse progression-free survival (PFS), independent of the International Prognostic Score. However, its role in HIV-associated HL is uncharacterised. We collected clinico-pathologic and treatment data from a prospective series of 44 HIV-associated HLs from 2000 to 2016. We evaluated circulating EBV DNA as a prognostic factor on uni- and multivariable analyses in relationship to the International Prognostic Index criteria. In 44 patients with HIV-associated HL, EBV was detected by in situ hybridisation in all diagnostic biopsies. Blood EBV DNA was detectable in 26 patients (59%) with a median of 600 copies/mL (range 0–161,000). EBV DNA was independent of CD4 cell count (p = 0.9) or HIV viral load (p = 0.6) and did not predict PFS (HR 1.6, 95% CI 0.39–6.7, p = 0.49). EBV DNA is not a prognostic trait in HIV-associated HL. Prognostication in HIV-associated HL should be solely based on the International Prognostic Index criteria.     

HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer

Introduction

Metastases to the brain from breast cancer have a high mortality, and basal-like breast cancers have a propensity for brain metastases. However, the mechanisms that allow cells to colonize the brain are unclear.

Methods

We used morphology, immunohistochemistry, gene expression and somatic mutation profiling to analyze 39 matched pairs of primary breast cancers and brain metastases, 22 unmatched brain metastases of breast cancer, 11 non-breast brain metastases and 6 autopsy cases of patients with breast cancer metastases to multiple sites, including the brain.

Results

Most brain metastases were triple negative and basal-like. The brain metastases over-expressed one or more members of the HER family and in particular HER3 was significantly over-expressed relative to matched primary tumors. Brain metastases from breast and other primary sites, and metastases to multiple organs in the autopsied cases, also contained somatic mutations in EGFR, HRAS, KRAS, NRAS or PIK3CA. This paralleled the frequent activation of AKT and MAPK pathways. In particular, activation of the MAPK pathway was increased in the brain metastases compared to the primary tumors.

Conclusions

Deregulated HER family receptors, particularly HER3, and their downstream pathways are implicated in colonization of brain metastasis. The need for HER family receptors to dimerize for activation suggests that tumors may be susceptible to combinations of anti-HER family inhibitors, and may even be effective in the absence of HER2 amplification (that is, in triple negative/basal cancers). However, the presence of activating mutations in PIK3CA, HRAS, KRAS and NRAS suggests the necessity for also specifically targeting downstream molecules.     

Severe raltegravir-associated rhabdomyolysis: a case report and review of the literature

Raltegravir (RAL), an HIV integrase inhibitor, may uncommonly induce an increase of serum creatine kinase (CK) both in na?ve and antiretroviral (ARV)-experienced HIV-positive patients. We report the case of severe rhabdomyolysis requiring hospitalization in an ARV-experienced HIV/hepatitis C co-infected patient treated with a RAL-containing drug regimen. Factors favouring a severe clinical occurrence of RAL-induced rhabdomyolysis from cases reported in literature are described.     

Extensive spatial training does not negate age differences in response latency

Previously, Nippak et al. [Nippak, P.M.D., Chan, A.D.F., Campbell, Z., Muggenburg, B., Head, E., Ikeda-Douglas, C., Murphy, H., Cotman, C.W., Milgram, N.W., 2003. Response latency in the canine: mental ability or mental strategy? Behav. Neurosci. 117 (5), 1066-1075] reported that young dogs respond significantly slower than aged dogs during the acquisition of a three-component delayed non-match to position (3-DNMP) task. Thus, we examined how age influences response latency (RL) when animals are trained extensively on the 3-DNMP task. Animals were separated into two groups based on their task sophistication. The first group comprised young (N=5) and aged (N=10) dogs that received extensive spatial training on a two-component delayed non-match to position task (2-DNMP) before 3-DNMP testing, while the second group of young (N=8) and aged (N=11) animals received extensive training on a variety of other non-spatial cognitive tasks between each 3-DNMP test period. RL age differences were absent following extensive 3-DNMP testing; however, other age-dependent performance differences emerged: all young animals learned the task and displayed RL slowing and superior response accuracy (RA) on the center-incorrect (CI) subtest, while several aged animals failed to learn the task and displayed no RL or RA subtest variations even when they acquired the task. Toates's [Toates, F., 1998. The interaction of cognitive and stimulus-response processes in the control of behaviour, Neurosci. Biobehav. Rev. 22 (1), 59-83] theory of RL and mental strategy was proposed to explain these age differences in response strategies: the fast-responding aged animals utilized stimulus-response strategies, while the slow-responding young animals adopted cognitive strategies, a specific requirement for solving the CI subtest.