Patient Reported Voice Outcome in Recurrent Respiratory Papillomatosis

Objectives/Hypothesis: To assess the impact of patient reported voice outcome on quality of life and emotional functioning in patients treated for recurrent respiratory papillomatosis (RRP). Study Design: Cross-sectional. Methods: All adult patients treated for RRP between 1984 and 2008 were asked to participate. Outcome measures were obtained from questionnaires including VHI (Voice Handicap Index), HADS (Hospital Anxiety and Depression Scale), 36-Item Short Form Health Survey (SF-36), and Utrechtse Coping List. Results: Out of 45 included patients, 34 (22 males, 12 females) participated (76%). Mean age was 52 years (range, 25-85 years). RRP was located only in the larynx in 90% of the cases. Adult onset RRP was diagnosed in 29 cases, juvenile onset RRP in 5. Median number of surgical procedures was five (range, 1-17). In this study cohort, 68% scored above the VHI cutoff point, and 18% had an increased risk for depression or anxiety disorders (HADS). VHI scores were related to age, time between consecutive surgeries, time since last surgery, and passive coping. They were not related to gender, onset of RRP, or location. VHI scores were related to the SF-36 subscales social functioning (r = -0.43) and mental health (r = -0.43). Conclusions: Patients with RRP often report voice problems in daily life, and this is related to (a passive) coping style, social functioning, and mental health. Psychosocial intervention targeting an adaptive coping style may be beneficial in selected cases. © 2009 The American Laryngological, Rhinological and Otological Society, Inc

Supplementary Material for: Irinotecan-Induced Dysarthria

Colorectal carcinomas are among the most common tumor types and are generally treated with palliative chemotherapy in case of metastatic disease. Here, we describe the case of a 46-year-old patient with metastatic rectal carcinoma who received second-line therapy with irinotecan and developed isolated transient dysarthria (with normal MR imaging of the brain) following each administration of irinotecan. Neurological and logopedical evaluation revealed that the dysarthria predominantly resulted from a reduced capacity in fine-tuning of motor functions of the tip of the tongue and a minimal reduction in the power of speech at labiodental contact. As hypoglossal nerve activity has been reported to be especially susceptible to cholinergic stimulation and irinotecan can cause cholinergic side effects by binding to and inactivating acetylcholinesterase, we suspect this mechanism to be responsible for irinotecan-induced dysarthria

Sensing of latent EBV infection through exosomal transfer of 5'pppRNA

Complex interactions between DNA herpesviruses and host factors determine the establishment of a life-long asymptomatic latent infection. The lymphotropic Epstein-Barr virus (EBV) seems to avoid recognition by innate sensors despite massive transcription of immunostimulatory small RNAs (EBV-EBERs). Here we demonstrate that in latently infected B cells, EBER1 transcripts interact with the lupus antigen (La) ribonucleoprotein, avoiding cytoplasmic RNA sensors. However, in coculture experiments we observed that latent-infected cells trigger antiviral immunity in dendritic cells (DCs) through selective release and transfer of RNA via exosomes. In ex vivo tonsillar cultures, we observed that EBER1-loaded exosomes are preferentially captured and internalized by human plasmacytoid DCs (pDCs) that express the TIM1 phosphatidylserine receptor, a known viraland exosomal target. Using an EBER-deficient EBV strain, enzymatic removal of 5'ppp, in vitro transcripts, and coculture experiments, we established that 5'pppEBER1 transfer via exosomes drives antiviral immunity in nonpermissive DCs. Lupus erythematosus patients suffer from elevated EBV load and activated antiviral immunity, in particular in skin lesions that are infiltrated with pDCs. We detected high levels of EBER1 RNA in such skin lesions, as well as EBV-microRNAs, but no intact EBV-DNA, linking non-cell-autonomous EBER1 presence with skin inflammation in predisposed individuals. Collectively, our studies indicate that virus-modified exosomes have a physiological role in the host-pathogen stand-off and may promote inflammatory disease