Immune suppression in gliomas

Journal of Neuro-Oncology - The overall survival in patients with gliomas has not significantly increased in the modern era, despite advances such as immunotherapy. This is in part due to their...     

The Safety of available immunotherapy for the treatment of glioblastoma

Introduction: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Current standard of care involves maximal surgical resection combined with adjuvant chemoradiation. Growing support exists for a role of immunotherapy in treating these tumors with the goal of targeted cytotoxicity. Here we review data on the safety for current immunotherapies being tested in GBM.

Areas covered: Safety data from published clinical trials, including ongoing clinical trials were reviewed. Immunotherapeutic classes currently under investigation in GBM include various vaccination strategies, adoptive T cell immunotherapy, immune checkpoint blockade, monoclonal antibodies, and cytokine therapies. Trials include children, adolescents, and adults with either primary or recurrent GBM.

Expert opinion: Based on the reviewed clinical trials, the current immunotherapies targeting GBM are safe and well-tolerated with minimal toxicities which should be noted. However, the gains in patient survival have been modest. A safe and well-tolerated combinatory immunotherapeutic approach may be essential for optimal efficacy towards GBM.     

Combined in silico and in vitro study of an aptasensor based on citrate-capped AuNPs for naked-eye detection of a critical biomarker of oxidative stress

An elevated level of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) in biosamples has been found to correlate to oxidative stress, and it has been assigned as a critical biomarker of various diseases. Herein, insights into the mechanisms of an aptasensor, based on citrate-capped gold nanoparticles (AuNPs), for 8-oxo-dG detection were elucidated using molecular dynamics (MD) simulations and validated experimentally. We found that the binding mechanism for binding between the anti-8-oxo-dG aptamer and 8-oxo-dG has the following characteristic stages: (i) adsorption stage, (ii) binding stage, and (iii) complex stabilization stage. Our simulations also reveal the binding sites between the anti-8-oxo-dG aptamer and 8-oxo-dG formed through hydrogen bonding during complex formation. A shortened anti-8-oxo-dG-aptamer was also engineered using in silico design, which was expected to improve the analytical performance of the colorimetric aptasensor. The mechanisms of the colorimetric aptasensor in the presence and absence of 8-oxo-dG were also investigated, and found to be in good agreement with the experiments. Complete understanding of the mechanism of the colorimetric aptasensor would open the door for development of novel naked-eye aptasensors.

A visual strategy for 8-oxo-dG monitoring based upon the dispersion of citrate-capped gold nanoparticles has been developed.     

Orthostatic hypotension is associated with new-onset atrial fibrillation: Systemic review and meta-analysis

IntroductionOrthostatic hypotension (OH) is common among elderly patients. Its presence may herald severe underlying comorbidities and be associated with a higher risk of mortality. Interestingly, recent studies suggest that OH is associated with new-onset atrial fibrillation (AF). However, a systematic review and meta-analysis of the literature has not been performed. We assessed the association between AF and OH through a systematic review of the literature and a meta-analysis.MethodsWe comprehensively searched the databases of MEDLINE and EMBASE from inception to November 2018. Published prospective or retrospective cohort studies that compared new-onset AF between male patients with and without OH were included. Data from each study were combined using the random-effects, generic inverse-variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals.ResultsFour studies from October 2010 to March 2018 were included in the meta-analysis involving 76,963 subjects (of which 3318 were diagnosed with OH). The presence of OH was associated with new-onset AF (pooled risk ratio 1.48; 95% confidence interval [1.21, 1.81], p?< 0.001; I2 = 69.4%). In hypertensive patients, analysis revealed an association between OH and the occurrence of new-onset AF (OR 1.46; 95% CI [1.27, 1.68], p < 0.001 with I2 = 0).ConclusionsOH was associated with new-onset AF up to 1.5-fold compared with those subjects without OH. The interplay between OH and AF is likely bidirectional.     

Baseline fragmented QRS increases the risk of major arrhythmic events in Brugada syndrome: Systematic review and meta‐analysis

Background

Fragmented QRS reflects disturbances in the myocardium predisposing the heart to ventricular tachyarrhythmias. Recent studies suggest that fragmented QRS (fQRS) is associated with major arrhythmic events in Brugada syndrome. However, a systematic review and meta‐analysis of the literature has not been done. We assessed the association between fQRS and major arrhythmic events in Brugada syndrome by a systematic review of the literature and a meta‐analysis.

Methods

We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2017. Included studies were published prospective or retrospective cohort studies that compared major arrhythmic events (ventricular fibrillation, sustained ventricular tachycardia, sudden cardiac arrest, or sudden cardiac death) in Brugada syndrome with fQRS versus normal QRS. Data from each study were combined using the random‐effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals.

Results

Nine studies from January 2012 to May 2017 were included in this meta‐analysis involving 2,360 subjects with Brugada syndrome (550 fQRS and 1,810 non‐fQRS). Fragmented QRS was associated with major arrhythmic events (pooled risk ratio =3.36, 95% confidence interval: 2.09‐5.38, p < .001, I² = 50.9%) as well as fatal arrhythmia (pooled risk ratio =3.09, 95% confidence interval: 1.40‐6.86, p = .005, I² = 69.7%).

Conclusions

Baseline fQRS increased major arrhythmic events up to 3‐fold. Our study suggests that fQRS could be an important tool for risk assessment in patients with Brugada syndrome.

     

Current infection rate of Giardia lamblia in two provinces of Thailand

The aim of this study was to survey for the current rate of Giardia lamblia infection in three different districts in two provinces of Thailand, Surin and Samut Sakhon, in March 2002, October 2003, and March 2004. Two districts are rural areas and another is sub-urban. Volunteers of any age from Surin Province and children aged between 5 to 7 years old from three secondary schools in Samut Sakhon were enrolled for the stool examination. The method used was stool examination by both simple smear and normal saline concentration technique on fresh collected feces. All samples were tested in duplicate. Out of 3,358 healthy individuals from rural Surin Province, 75 cases (2.2%) were found positive for G. lamblia, 30 of which were below 10 years of age. By comparison, 656 individuals from sub-urban Samut Sakhon Province volunteered and 43 (6.5%) were positive for G. lamblia. Other intestinal parasites, both helminth and protozoa, were also identified from these two groups: hookworm, Enterobius vermicularis, Strongyloides stercoralis, Trichuris trichiura, Taenia species, Entamoeba histolytica, Entamoeba coli, Endolimax nana, and Blastocystis hominis. From this study, the data showed that parasitic infection acquired via fecal-oral route is still a significant problem for these two provinces of Thailand.