Survival After Stereotactic Body Radiation Therapy for Clinically Diagnosed or Biopsy-Proven Early-Stage NSCLC: A Systematic Review and Meta-Analysis

Introduction

Stereotactic body radiation therapy (SBRT) is a promising curative treatment for early-stage NSCLC. It is unclear if survival outcomes for SBRT are influenced by a lack of pathological confirmation of malignancy and staging of disease in these patients. In this systematic review and meta-analysis, we assess survival outcomes after SBRT in studies with patients with clinically diagnosed versus biopsy-proven early-stage NSCLC.

Stigma in youth with Tourette’s syndrome: a systematic review and synthesis

Tourette’s syndrome (TS) is a childhood onset neurodevelopmental disorder, characterised by tics. To our knowledge, no systematic reviews exist which focus on examining the body of literature on stigma in association with children and adolescents with TS. The aim of the article is to provide a review of the existing research on (1) social stigma in relation to children and adolescents with TS, (2) self-stigma and (3) courtesy stigma in family members of youth with TS. Three electronic databases were searched: PsycINFO, PubMed and Web of Science. Seventeen empirical studies met the inclusion criteria. In relation to social stigma in rating their own beliefs and behavioural intentions, youth who did not have TS showed an unfavourable attitude towards individuals with TS in comparison to typically developing peers. Meanwhile, in their own narratives about their lives, young people with TS themselves described some form of devaluation from others as a response to their disorder. Self-degrading comments were denoted in a number of studies in which the children pointed out stereotypical views that they had adopted about themselves. Finally, as regards courtesy stigma, parents expressed guilt in relation to their children’s condition and social alienation as a result of the disorder. Surprisingly, however, there is not one study that focuses primarily on stigma in relation to TS and further studies that examine the subject from the perspective of both the ‘stigmatiser’ and the recipient of stigma are warranted.     

Phantom-based assessment of motion and needle targeting accuracy of robotic devices for magnetic resonance imaging-guided needle biopsy

Background

The current study proposes simple methods for assessing the performance of robotic devices intended for Magnetic Resonance Imaging (MRI)-guided needle biopsy.

Methods

In-house made agar-based breast phantoms containing biopsy targets served as the main tool in the evaluation process of an MRI compatible positioning device comprising a needle navigator. The motion accuracy of mechanical stages was assessed by calliper measurements. Laboratory evaluation of needle targeting included a repeatability phantom test and a laser-based method. The accuracy and repeatability of needle targeting was also assessed by MRI.

Results

The maximum error of linear motion for steps up to 10 mm was 0.1 mm. Needle navigation relative to the phantom and alignment with the various biopsy targets were performed successfully in both the laboratory and MRI settings. The proposed biopsy phantoms offered tissue-like signal in MRI and good haptic feedback during needle insertion.

Conclusions

The proposed methods could be valuable in the process of validating the accuracy of MRI-guided biopsy robotic devices in both laboratory and real environments.     

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings,histological profile,treatments, and outcomes

ObjectiveThis large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis.MethodsThe medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments.ResultsOf all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%).ConclusionsIn this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.     

A positive-feedback mechanism promotes reovirus particle conversion to the intermediate associated with membrane penetration

Membrane penetration by reovirus is associated with conversion of a metastable intermediate, the ISVP, to a further-disassembled particle, the ISVP*. Factors that promote this conversion in cells are poorly understood. Here, we report the in vitro characterization of a positive-feedback mechanism for promoting ISVP* conversion. At high particle concentration, conversion approximated second-order kinetics, and products of the reaction operated in trans to promote the conversion of target ISVPs. Pore-forming peptide μ1N, which is released from particles during conversion, was sufficient for promoting activity. A mutant that does not undergo μ1N release failed to exhibit second-order conversion kinetics and also failed to promote conversion of wild-type target ISVPs. Susceptibility of target ISVPs to promotion in trans was temperature dependent and correlated with target stability, suggesting that capsid dynamics are required to expose the interacting epitope. A positive-feedback mechanism of promoting escape from the metastable intermediate has not been reported for other viruses but represents a generalizable device for sensing a confined volume, such as that encountered during cell entry.     

The Efficacy of Disinfection on Modified Vaccinia Ankara and African Swine Fever Virus in Various Forest Soil Types

African swine fever (ASF) has become a global threat to the pig industry and wild suids. Within Europe, including Germany, affected wild boar populations play a major role. Fencing and carcass removal in combination with the reduction in environmental contamination are key to control further spread. The handling of the ASF virus (ASFV) is restricted to high-containment conditions in Germany. According to the regulation of the German Veterinarian Society (DVG), modified vaccinia Ankara virus (MVAV) is the virus of choice to determine the efficacy of disinfection for enveloped viruses. The aim of this study was to use the MVAV as a guide to select the best possible disinfectant solution and concentration for the inactivation of ASFV in soil. Both viruses were tested simultaneously. In this study, two layers (top and mineral soil) of soil types from six different locations in Saxony, Germany, were collected. The tenacity of ASFV and MVAV were tested at various time points (0.5 to 72 h). The capabilities of different concentrations of peracetic acid and citric acid (approx. 0.1 to 2%) to inactivate the viruses in the selected soil types with spiked high protein load were examined under appropriate containment conditions. Around 2–3 Log₁₀ (TCID₅₀) levels of reduction in the infectivity of both ASFV and MVAV were observed in all soil types starting after two hours. For MVAV, a 4 Log₁₀ loss was recorded after 72 h. A total of 0.1% of peracetic acid (5 L/m²) was sufficient to inactivate the viruses. A 4 log₁₀ reduction in the infectivity of MVAV was noticed by applying 1% citric acid, while a 2 log₁₀ decline was recorded with ASFV. In conclusion, comparing MVAV to ASFV for efficacy screening of disinfectant solutions has revealed many similarities. Peracetic acid reduced the infectivity of both viruses independently of the soil type and the existence of a high organic soiling.     

Sensory ataxia rating scale: Development and validation of a functional scale for patients with sensory neuronopathies

Sensory neuronopathies (SN) result from dorsal root ganglia damage and manifest with a combination of sensory deficits and proprioceptive ataxia. Characterization of the natural history and development of therapeutic trials are hampered by the lack of clinical scales that capture the whole spectrum of SN‐related manifestations. We propose and validate a rating instrument for SN. Three experienced neuromuscular specialists developed items to rate SN. The resultant instrument was later validated by the assessment of the intra‐class correlation coefficient, for inter‐rater validity in 48 SN patients, and later in a smaller subset of 16 patients to assess its intra‐rater validity. Standardized Crombach's alpha and Oblimin rotation analysis were performed to verify internal consistency and items' relationship, respectively. Evaluation of Sensory Ataxia Rating Scale (SEARS)'s external validity was performed by comparison to: scale for the assessment and rating of ataxia (SARA), Beck balance scale (BBS), and INCAT sensory sum score (ISS). A 10‐item scale with an intra‐class correlation coefficient >0.95 for intra‐ and inter‐rating measurements with a good internal consistency (standardized Cronbach's alpha of 0.83) were observed. There was a normal distribution of the scores without a floor or ceiling effect. A moderate to good correlation between SEARS and SARA, BBS, and ISS was observed. SEARS is a reliable, easy‐to‐perform and consistent instrument to rate SN. Larger cohorts and multicenter studies are needed to validate its usefulness towards possible treatment trials.