Synergy of BCL2 and histone deacetylase inhibition against leukemic cells from cutaneous T-cell lymphoma patients.

The presence and degree of peripheral blood involvement in patients with cutaneous T-cell lymphoma (CTCL) portend a worse clinical outcome. Available systemic therapies for CTCL may variably decrease tumor burden and improve quality of life, but offer limited effects on survival; thus, novel approaches to the treatment of advanced stages of this non-Hodgkin lymphoma are clearly warranted. Mutational analyses of CTCL patient peripheral blood malignant cell samples suggested the antiapoptotic mediator B-cell lymphoma 2 (BCL2) as a potential therapeutic target. To test this, we developed a screening assay for evaluating the sensitivity of CTCL cells to targeted molecular agents, and compared a novel BCL2 inhibitor, venetoclax, alone and in combination with a histone deacetylase (HDAC) inhibitor, vorinostat or romidepsin. Peripheral blood CTCL malignant cells were isolated from 25 patients and exposed ex vivo to the 3 drugs alone and in combination, and comparisons were made to 4 CTCL cell lines (Hut78, Sez4, HH, MyLa). The majority of CTCL patient samples were sensitive to venetoclax, and BCL2 expression levels were negatively correlated (r = -0.52; P =018) to 50% inhibitory concentration values. Furthermore, this anti-BCL2 effect was markedly potentiated by concurrent HDAC inhibition with 93% of samples treated with venetoclax and vorinostat and 73% of samples treated with venetoclax and romidepsin showing synergistic effects. These data strongly suggest that concurrent BCL2 and HDAC inhibition may offer synergy in the treatment of patients with advanced CTCL. By using combination therapies and correlating response to gene expression in this way, we hope to achieve more effective and personalized treatments for CTCL.

Bullous systemic lupus erythematosus in a 6-year-old boy.

Bullous systemic lupus erythematosus (BSLE) is a rare subepidermal blistering disorder characterized by an acute vesiculobullous eruption in a subset of individuals with systemic lupus erythematosus. BSLE most commonly affects young women and only rarely affects children. Herein we report a rare case of BSLE in a 6-year-old boy.

Prevalence of obstructive sleep apnea in patients with posttraumatic stress disorder and its impact on adherence to continuous positive airway pressure therapy: a meta-analysis.

OBJECTIVE: Although some authors have recently investigated the co-occurrence of posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA), the topic remains insufficiently studied. The aim of this meta-analysis was to detect the pooled prevalence of OSA in PTSD and its impact on adherence to continuous positive airway pressure (CPAP) therapy. METHODS: We conducted a search for articles published until August 20, 2016, in PubMed, Embase, the Cochrane Library, and PsycINFO. The literature search identified 194 articles, and 12 studies were included in the meta-analysis. RESULTS: The pooled prevalence rates of OSA based on different apnea-hypopnea index (AHI) criteria in PTSD patients was 75.7% (95% confidence interval [CI] = 44.1-92.5%) (AHI ≥5) and 43.6% (95% CI = 20.6-69.7%) (AHI ≥10), respectively. Subgroup analysis showed that there was a significant difference between the prevalence of OSA in veterans with PTSD compared to nonveterans or mixed samples. Patients with PTSD and OSA demonstrated significantly lower adherence to CPAP therapy (regular use: g = -0.658, 95% CI = -0.856 to -0.460; time of average use per night: g = -0.873, 95% CI = -1.550 to -0.196) compared with those with OSA alone. CONCLUSIONS: OSA is commonly seen in patients with PTSD. Given its negative impact on the adherence to CPAP therapy, the possibility of OSA should be monitored carefully in patients with PTSD.

Deficits in attention performance are associated with insufficiency of slow-wave sleep in insomnia.

OBJECTIVE: Cognitive impairment is associated with insomnia. However, there is a lack of evidence suggesting a link between insomnia and cognitive dysfunction in objective testing. The objectives of our current study were to assess the differences in components of attentional performance between primary insomnia patients and normal-sleeping controls and to examine potential predictors of attention impairment in patients with insomnia. METHODS: We studied 36 patients (age 40.39 ± 12.36 years; 57.1% male) with insomnia and 25 normal-sleeping controls (age 39.88 ± 12.50 years; 52.9% male) who underwent one-night polysomnography followed by Multiple Sleep Latency Test (MSLT) and Attention Network Task (ANT). ANT reflected three attentional networks termed the alerting, orienting, and executive control networks. RESULTS: After controlling for age, gender, body mass index, depression, anxiety, and education levels, patients with insomnia scored higher on the executive control variable of the ANT compared with normal-sleeping controls (96.75 ± 7.60 vs. 57.00 ± 10.49, p = 0.01). This higher score was independently associated with insufficiency of slow-wave sleep during nighttime sleep (ß = -0.38, p = 0.04). CONCLUSION: Our findings suggest that insomnia is associated with deficits in executive control of attention and that the underlying mechanism may be insufficiency of slow-wave sleep in chronic insomnia.