Randomized prospective trial of fractionated stereotactic radiosurgery with chemotherapy versus chemotherapy alone for bevacizumab-resistant high-grade glioma

Journal of Neuro-Oncology - Outcomes for patients with recurrent high-grade glioma (HGG) progressing on bevacizumab (BEV) are dismal. Fractionated stereotactic radiosurgery (FSRS) has been shown to...     

Hiking in Suicidal Patients: Neutral Effects on Markers of Suicidality

Background

Regular physical activity promotes physical and mental health. Psychiatric patients are prone to a sedentary lifestyle, and accumulating evidence has identified physical activity as a supplemental treatment option.

Methods

This prospective, randomized, crossover study evaluated the effects of hiking in high-risk suicidal patients (n = 20) who performed 9 weeks of hiking (2-3 hikes/week, 2-2.5 hours each) and a 9-week control period.

Results

All patients participated in the required 2 hikes per week and thus showed a compliance of 100%. Regular hiking led to significant improvement in maximal exercise capacity (hiking period Δ: +18.82 ± 0.99 watt, P < .001; control period: P = .134) and in aerobic capability at 70% of the individual heart rate reserve (hiking period Δ: +8.47 ± 2.22 watt; P = .010; control period: P = .183). Cytokines, associated previously with suicidality (tumor necrosis factor-α, interleukin-6, S100), remained essentially unchanged.

Conclusions

Hiking is an effective and safe form of exercise training even in high-risk suicidal patients. It leads to a significant improvement in maximal exercise capacity and aerobic capability without concomitant deterioration of markers of suicidality. Offering this popular mode of exercise to these patients might help them to adopt a physically more active lifestyle.     

Liquid biopsies for colorectal cancer: a narrative review of ongoing clinical trials and the current use of this technology at a comprehensive cancer center

ObjectiveIn this review, we summarize ongoing clinical trials involving liquid biopsies (LB) for colorectal cancer (CRC), outlining the current landscape and the future implementation of this technology. We also describe the current use of LB in CRC treatment at our institution, the Mayo Clinic Enterprise.BackgroundThe use of LB in CRC treatment merits close attention. Their role is being evaluated in the screening, non-intervention, intervention, and surveillance settings through many active trials. This, coupled with the technique’s rapid integration into clinical practice, creates constant evolution of care.MethodsReview of ClinicalTrials.gov was performed identifying relevant and active trials involving LB for CRC. “Colorectal cancer” plus other terms including “liquid biopsies” and “ctDNA” were used as search terms, identifying 35 active trials.ConclusionsLB use for the CRC is actively being investigated and requires close attention. Based on current evidence, Mayo Clinic Enterprise currently uses LB in the non-interventional, interventional and surveillance setting, but not for screening. Results of these trials may further establish the use of LB in the management of CRC.     

The role and strategy of ISoP in global pharmacovigilance

Applying the WHO definition of pharmacovigilance, the International Society of Pharmacovigilance, (ISoP) is concerned with all aspects of medicine safety. The safety of patients exposed to medicines depends on a wide variety of factors, where the understanding of each factor is associated with its own professional competence and skillset. For pharmacovigilance systems to work efficiently, a broad understanding of the necessary contribution of each of the different scientific competence areas and professional skills is required. ISoP is an independent, not-for-profit international professional organization, concerned with the best interest of patients exposed to pharmaceutical interventions in all healthcare systems in the world. ISoP offers an open platform for professionals from around the world with different expertise and skillsets, to network and exchange information and knowledge in a friendly environment. The society wishes to become a stronger global voice, speaking up in favour of patient safety and to be at the frontline of the global patient safety movement.     

A pattern of association between clinical form of vitiligo and disease-related variables in a Brazilian population

Background

Vitiligo classification systems are often based exclusively on the number and distribution of the white patches. To what extend these classification protocols reflect possible different pathophysiological basis for vitiligo or carry any prognostic value is currently unknown.

Objective

To investigate patterns of association between type of vitiligo and common disease-related variables, in order to advance on the understanding of the exact nature of different clinical forms of disease, as well as to identify features with prognostic value for clinical progression of early diagnosed vitiligo.

Materials and methods

This is a cross-sectional study of a population sample from south of Brazil composed of 586 independent vitiligo-affected individuals. Different strategies of case-control analysis were employed to test for association between the three most common vitiligo clinical types and age of onset, family history of vitiligo, occurrence of Köebner phenomenon (KP) and presence of autoimmune co-morbidity.

Results

Individuals affected by segmental vitiligo showed lower average age of onset (16 years) when compared with vulgaris (23.9 years) and acrofacial cases (29 years) (p < 0.001). The distribution of occurrence of KP, family history of vitiligo and co-occurrence of autoimmune disease followed a gradient pattern, with high, intermediate and low chance of occurrence of all three variables observed for vulgaris, acrofacial and segmental vitiligo, respectively (p < 0.001 for overall distribution).

Conclusion

Results indicate a uniform pattern of association between vitiligo clinical forms and KP, positive vitiligo family history and occurrence of co-morbidity autoimmune. The impact of the observed pattern of association over disease prognosis and classification is discussed.     

Development of a focused oligonucleotide-array comparative genomic hybridization chip for clinical diagnosis of genomic imbalance

BACKGROUND: Submicroscopic genomic imbalance underlies well-defined microdeletion and microduplication syndromes and contributes to general developmental disorders such as mental retardation and autism. Array comparative genomic hybridization (CGH) complements routine cytogenetic methods such as karyotyping and fluorescence in situ hybridization (FISH) for the detection of genomic imbalance. Oligonucleotide arrays in particular offer advantages in ease of manufacturing, but standard arrays for single-nucleotide polymorphism genotyping or linkage analysis offer variable coverage in clinically relevant regions. We report the design and validation of a focused oligonucleotide-array CGH assay for clinical laboratory diagnosis of genomic imbalance. METHODS: We selected >10 000 60-mer oligonucleotide features from Agilent's eArray probe library to interrogate all subtelomeric and pericentromeric regions and 95 additional clinically relevant regions for a total of 179 loci. Sensitivity and specificity were measured for 105 patient samples, including 51 with known genomic-imbalance events, as detected by bacterial artificial chromosome-based array CGH, FISH, or multiplex ligation-dependent probe amplification. RESULTS: Focused array CGH detected all known regions of genomic imbalance in 51 validation samples with 100% concordance and an excellent signal-to-noise ratio. The mean SD among log(2) ratios of all noncontrol features without copy number alteration was 0.062 (median, 0.055). Clinical testing of another 211 samples from individuals with developmental delay, unexplained mental retardation, dysmorphic features, or multiple congenital anomalies revealed genomic imbalance in 25 samples (11.9%). CONCLUSIONS: This focused oligonucleotide-array CGH assay, a flexible, robust method for clinically diagnosing genetic disorders associated with genomic imbalance, offers appreciable advantages over currently available platforms.     

Closed-Loop Neurofeedback of α Synchrony during Goal-Directed Attention

α Oscillations in sensory cortex, under frontal control, desynchronize during attentive preparation. Here, in a selective attention study with simultaneous EEG in humans of either sex, we first demonstrate that diminished anticipatory α synchrony between the mid-frontal region of the dorsal attention network and ventral visual sensory cortex [frontal-sensory synchrony (FSS)] significantly correlates with greater task performance. Then, in a double-blind, randomized controlled study in healthy adults, we implement closed-loop neurofeedback (NF) of the anticipatory α FSS signal over 10 d of training. We refer to this closed-loop experimental approach of rapid NF integrated within a cognitive task as cognitive NF (cNF). We show that cNF results in significant trial-by-trial modulation of the anticipatory α FSS measure during training, concomitant plasticity of stimulus-evoked α/θ responses, as well as transfer of benefits to response time (RT) improvements on a standard test of sustained attention. In a third study, we implement cNF training in children with attention deficit hyperactivity disorder (ADHD), replicating trial-by-trial modulation of the anticipatory α FSS signal as well as significant improvement of sustained attention RTs. These first findings demonstrate the basic mechanisms and translational utility of rapid cognitive-task-integrated NF.SIGNIFICANCE STATEMENT When humans prepare to attend to incoming sensory information, neural oscillations in the α band (8–14 Hz) undergo desynchronization under the control of prefrontal cortex. Here, in an attention study with electroencephalography, we first show that frontal-sensory synchrony (FSS) of α oscillations during attentive preparation significantly correlates with task performance. Then, in a randomized controlled study in healthy adults, we show that neurofeedback (NF) training of this α FSS signal within the attention task is feasible. We show that this rapid cognitive NF (cNF) approach engenders plasticity of stimulus-evoked neural responses, and improves performance on a standard test of sustained attention. In a final study, we implement cNF in children with attention deficit hyperactivity disorder (ADHD), replicating the improvement of sustained attention found in adults.