HDR brachytherapy boost using MR-only workflow for intermediate- and high-risk prostate cancer: 8-year results of a pilot study

PurposeTo report 8-year clinical outcome with high-dose-rate brachytherapy (HDRBT) boost using MRI-only workflow for intermediate (IR) and high-risk (HR) prostate cancer (PC) patients.Methods and MaterialsFifty-two patients were treated with 46–60 Gy of 3D conformal radiotherapy preceded and/or followed by a single dose of 8–10 Gy MRI-guided HDRBT. Interventions were performed in a 0.35 T MRI scanner. Trajectory planning, navigation, contouring, catheter reconstruction, and dose calculation were exclusively based on MRI images. Biochemical relapse-free- (BRFS), local relapse-free- (LRFS), distant metastasis-free- (DMFS), cancer-specific-(CCS) and overall survival (OS) were analyzed. Late morbidity was scored using the Common Terminology Criteria for Adverse Events (CTCAE 4.0) combined with RTOG (Radiation Therapy Oncology Group) scale for urinary toxicity and rectal urgency (RU) determined by Yeoh.ResultsMedian follow-up time was 107 (range: 19–143) months. The 8-year actuarial rates of BRFS, LRFS, DMFS, CSS and OS were 85.7%, 97%, 97.6%, and 77.6%, respectively. There were no Gr.3 GI side effects. The 8-year actuarial rate of Gr.2 proctitis was 4%. The 8-year cumulative incidence of Gr.3 GU side effects was 8%, including two urinary stenoses (5%) and one cystitis (3%). EPIC urinary and bowel scores did not change significantly over time.ConclusionsMRI-only HDR-BT boost with moderate dose escalation provides excellent 8-year disease control with a favorable toxicity profile for IRPC and HRPC patients. Our results support the clinical importance of MRI across the BT workflow.     

Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent conversion from undifferentiated connective tissue disease to definitive systemic autoimmune disorders

A shift in the balance between Th17-cells and regulatory T-cells (Treg) is an important feature of systemic autoimmune diseases (SAID), and may also contribute to their development. Hereby, we assessed the distribution of peripheral Th17 and Treg-cells in patients with undifferentiated connective tissue disease (UCTD), the forerunner of SAIDs and followed these parameters during the development towards definitive SAIDs. Fifty-one UCTD patients were investigated and followed-up for 3 years. Flow cytometry was used to identify and follow three cell-populations: Th17-cells (CD4+IL-17+ T-cells), natural regulatory T-cells (CD4⁺CD25^brightFoxP3⁺; nTregs) and IL-10 producing Type-1 regulatory T-cells (CD4+IL-10+ T-cells; Tr1). Altogether 37.3% of these patients progressed into SAIDs. Th17-cells were increased in UCTD vs. controls, which further increased in those, whom developed SAIDs eventually. The Th17/nTreg ratio gradually increased from controls through UCTD patients, reaching the highest values in SAID-progressed patients. Regarding the Th17/Tr1 ratios, a similar tendency was observed moreover Th17/Tr1 could distinguish between UCTD patients with, or without subsequent SAID progression in a very early UCTD stage. Various immunoserological markers showed association with Th17 and Th17/nTreg at baseline, indicating the consecutive development of a distinct SAID. The derailed Th17/Treg balance may contribute to disease progression therefore could function as a prognostic marker.     

Erratum: Reciprocity of exposure time and irradiance on energy density during photoradiation on wound healing in a murine pressure ulcer model

In this original published article, Dr. Peter, Sr's name was misprinted. It should be Timothy A. Peter, Sr.     

Rhesus Macaque Model of Chronic Opiate Dependence and Neuro-AIDS: Longitudinal Assessment of Auditory Brainstem Responses and Visual Evoked Potentials

Our work characterizes the effects of opiate (morphine) dependence on auditory brainstem and visual evoked responses in a rhesus macaque model of neuro-AIDS utilizing a chronic continuous drug delivery paradigm. The goal of this study was to clarify whether morphine is protective, or if it exacerbates simian immunodeficiency virus (SIV)-related systemic and neurological disease. Our model employs a macrophage tropic CD4/CCR5 coreceptor virus, SIV_mac239 (R71/E17), which crosses the blood-brain barrier shortly after inoculation and closely mimics the natural disease course of human immunodeficiency virus infection. The cohort was divided into three groups: morphine only, SIV only, and SIV + morphine. Evoked potential (EP) abnormalities in subclinically infected macaques were evident as early as 8 weeks postinoculation. Prolongations in EP latencies were observed in SIV-infected macaques across all modalities. Animals with the highest cerebrospinal fluid viral loads and clinical disease showed more abnormalities than those with subclinical disease, confirming our previous work (Raymond et al., J Neurovirol 4:512–520, 1998; J Neurovirol 5:217–231, 1999; AIDS Res Hum Retroviruses 16:1163–1173, 2000). Although some differences were observed in auditory and visual evoked potentials in morphine-treated compared to morphine-untreated SIV-infected animals, the effects were relatively small and not consistent across evoked potential type. However, morphine-treated animals with subclinical disease had a clear tendency toward higher virus loads in peripheral and central nervous system tissues (Marcario et al., J Neuroimmune Pharmacol 3:12–25, 2008) suggesting that if had been possible to follow all animals to end-stage disease, a clearer pattern of evoked potential abnormality might have emerged. This work was supported by NIH grants DA12827, HD02528, and COBRE P20RR16443. Meeting presentations: Psychoneuroimmunology Research Society, May 2007; USA-Caribbean Conference: HIV/AIDS and Drug Abuse, Dec 2006; Society on NeuroImmune Pharmacology, April 2006 and April 2005; Association for Research in Otolaryngology 29th MidWinter Meeting, Feb. 2006; Society for Neuroscience, Oct. 2004.     

The influence of semantic processing on phonological decisions in children and adults: a magnetoencephalography (MEG) study.

PURPOSE: To examine the behavioral effects and neural activation patterns associated with implicit semantic processing influences on phonological judgments during reading in children and adults. METHOD: Whole-head magnetoencephalography (MEG) recordings were obtained from 2 groups, children (9-13 years) and adults, performing a homophone judgment task. The stimuli consisted of pairs of sequentially presented written words that were either homophones, synonym foils, or unrelated control words. RESULTS: The difference in the time taken to respond to synonym pairs relative to control pairs of stimuli, called the semantic interference effect (SIE), was, on average, 24 ms for adults and 86 ms for children. Source analysis of the MEG data using minimum-norm estimation (MNE) yielded less activation in the adults for the synonym condition compared with the control condition in right anterior temporal and inferior frontal cortex 300-500 ms after the onset of the 2nd word in a pair, suggestive of semantic priming as well as inhibition of the SIE. A similar priming effect was observed for the children in left-anterior temporal cortex. CONCLUSION: The observed group differences in the magnitude of the SIE and brain activation patterns may reflect developmental differences in the effects of semantic information on phonological decisions during word processing.