Intensity modulated radiation therapy (IMRT) in the management of prostate cancer

Intensity modulated radiation therapy (IMRT) is gaining widespread use in the radiation therapy community. Prostate cancer is the ideal target for IMRT due to the growing body of literature supporting dose escalation and normal tissue limitations. The need for dose escalation and the limits of conventional radiation therapy necessitate precise patient and prostate localization as well as advanced treatment delivery. The treatment of prostate cancer has been dramatically altered by the introduction of technology that can focus on the target while avoiding normal tissue. IMRT is evolving as the treatment of the future for prostate cancer.     

The epidemiology of childhood psoriasis: a scoping review

Psoriasis is an inflammatory noncommunicable skin disease that affects both adults and children. At present, the epidemiology and natural history of psoriasis are not widely understood. This scoping review aimed to map the existing literature on the epidemiology of childhood psoriasis, identify research gaps for future studies and provide a comprehensive, clinically useful review. Search strategies were developed for Ovid Medline, Ovid Embase, Google Scholar and hand searching. In total, 131 articles met the inclusion criteria and were mapped; 107 articles were included for data extraction. Over the last 25 years there has been a dramatic increase in the volume of published observational epidemiological studies on childhood psoriasis. The majority were case series or cross‐sectional studies, concentrated in Europe, Asia and North America. The prevalence of childhood psoriasis was found to be higher in European countries, older children and girls. Up to 48·8% of children had a family history of psoriasis in a first‐degree relative. The most frequent subtype was plaque psoriasis and the most common initial sites of presentation were the scalp, limbs and trunk. Specific genetic differences have been found between child‐onset and adult‐onset populations. Case–control and cohort studies investigating risk factors for psoriasis onset, comorbidities and long‐term health outcomes were extremely limited. The choice of study design and heterogeneity in methodology limit the validity and generalizability of the information, consistency of the results, and comparability of the studies. Well‐designed epidemiological studies are needed to provide precise and consistent information about the frequency and clinical presentation, risk factors, associated diseases and long‐term outcomes in childhood psoriasis.     

Lung expansion, tidal exchange, and formation of the functional residual capacity during resuscitation of asphyxiated neonates.

Ventilatory exchange and endotracheal and esophageal pressures were measured during resuscitation of asphyxiated neonates born by cesarean section. In contrast to spontaneously breathing, vaginally born babies, an opening pressure had to be exceeded before lung expansion occurred. Subsequently there was usually a gradual increase in gaseous exchange over the first few lung inflations. A further rise in lung compliance occurred with the baby's inspiratory efforts. The functional residual capacity was formed with or without active inspiratory efforts by the baby, although gaseous retention occurred more rapidly as a result of the infant's inspiration.     

The tolerance of gastrointestinal organs to stereotactic body radiation therapy: what do we know so far?

As stereotactic body radiation therapy (SBRT) for gastrointestinal (GI) gains popularity, there is a need to optimize doses and fractionation to minimize GI toxicity. GI organs that have classically developed radiation-induced toxicity include the liver & biliary system, small bowel, esophagus, and rectum. While the literature quantifies dose restrictions for these organs under standard fractionation, there is limited data regarding toxicity with the ablative dose schedules used in SBRT. We conducted a review of the literature to identify prospective and retrospective studies that detail GI toxicities when SBRT was employed. Based on the literature, the median SBRT dose for abdominal and thoracic tumors ranged from 24 to 60 Gy, at 5 to 25 Gy per fraction. The respective observed frequencies of grade 3 and 4 toxicities for the liver, biliary system, small bowel, and esophagus were variable among different studies. Typically, patients who suffered grade 3 and 4 toxicities were more likely to have had some form of systemic therapy as well. The effect of dose, fractionation, timing, and volume on GI toxicities has been described in the literature but more data is necessary to develop uniform treatment guidelines for SBRT.     

Newcastle disease virotherapy induces long‐term survival and tumor‐specific immune memory in orthotopic glioma through the induction of immunogenic cell death

The oncolytic features of several naturally oncolytic viruses have been shown on Glioblastoma Multiforme cell lines and in xenotransplant models. However, orthotopic glioma studies in immunocompetent animals are lacking. Here we investigated Newcastle disease virus (NDV) in the orthotopic, syngeneic murine GL261 model. Seven days after tumor induction, mice received NDV intratumorally. Treatment significantly prolonged median survival and 50% of animals showed long‐term survival. We demonstrated immunogenic cell death (ICD) induction in GL261 cells after NDV infection, comprising calreticulin surface exposure, release of HMGB1 and increased PMEL17 cancer antigen expression. Uniquely, we found absence of secreted ATP. NDV‐induced ICD occurred independently of caspase signaling and was blocked by Necrostatin‐1, suggesting the contribution of necroptosis. Autophagy induction following NDV infection of GL261 cells was demonstrated as well. In vivo, elevated infiltration of IFN‐γ⁺ T cells was observed in NDV‐treated tumors, along with reduced accumulation of myeloid derived suppressor cells. The importance of a functional adaptive immune system in this paradigm was demonstrated in immunodeficient Rag2^?/? mice and in CD8⁺ T cell depleted animals, where NDV slightly prolonged survival, but failed to induce long‐term cure. Secondary tumor induction with GL261 cells or LLC cells in mice surviving long‐term after NDV treatment, demonstrated the induction of a long‐term, tumor‐specific immunological memory response by ND virotherapy. For the first time, we describe the therapeutic activity of NDV against GL261 tumors, evidenced in an orthotopic mouse model. The therapeutic effect relies on the induction of ICD in the tumor cells, which primes adaptive antitumor immunity.     

Investigating the Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Cortical Excitability in Healthy Males

ObjectivesAs a potential treatment for epilepsy, transcutaneous auricular vagus nerve stimulation (taVNS) has yielded inconsistent results. Combining transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) can be used to investigate the effect of interventions on cortical excitability by evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs). The goal of this study is to objectively evaluate the effect of taVNS on cortical excitability with TMS-EMG and TMS-EEG. These findings are expected to provide insight in the mechanism of action and help identify more optimal stimulation paradigms.Materials and MethodsIn this prospective single-blind cross-over study, 15 healthy male subjects underwent active and sham taVNS for 60 min, using a maximum tolerated stimulation current. Single and paired pulse TMS was delivered over the right-sided motor hotspot to evaluate MEPs and TEPs before and after the intervention. MEP statistical analysis was conducted with a two-way repeated measures ANOVA. TEPs were analyzed with a cluster-based permutation analysis. Linear regression analysis was implemented to investigate an association with stimulation current.ResultsMEP and TEP measurements were not affected by taVNS in this study. An association was found between taVNS stimulation current and MEP outcome measures indicating a decrease in cortical excitability in participants who tolerated higher taVNS currents. A subanalysis of participants (n = 8) who tolerated a taVNS current ≥2.5 mA showed a significant increase in the resting motor threshold, decrease in MEP amplitude and modulation of the P60 and P180 TEP components.ConclusionstaVNS did not affect cortical excitability measurements in the overall population in this study. However, taVNS has the potential to modulate specific markers of cortical excitability in participants who tolerate higher stimulation levels. These findings indicate the need for adequate stimulation protocols based on the recording of objective outcome parameters.     

Identification of copy number alterations and its association with pathological features in clear cell and papillary RCC

We report and characterize the copy number alterations (CNAs) in 35 clear cell and 12 papillary renal cell carcinomas (RCC) using Affymetrix 100K SNP arrays. Novel gain and loss regions are identified in both subtypes. In addition, statistically significant CNA are detected and associated with the pathological features: VHL mutation status, tumor grades, and sarcomatoid component in clear cell RCC and in types 1 and 2 of papillary RCC. Florescence in situ hybridization confirmed the copy number gain in the transforming growth factor, beta-induced gene (TGFBI), which is a possible oncogene for clear cell RCC.     

Systematic quantification of histologic ventricular fibrosis in isolated mitral valve prolapse and sudden cardiac death

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