2 Minute Medicine Rewind June 10, 2018

The safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults: a double-blind, single-centre phase 1 study

Oral live-attenuated polio vaccines (OPV) and injected inactivated polio vaccines IPV) have helped eradicate wild polioviruses. However, there is still a need to develop new vaccines due to risk of outbreaks of vaccine-derived polioviruses. In the process of developing new vaccines, it is important to study the safety of the viruses and possible release into the environment. In this double-blind phase 1 trial, investigators randomized 30 participants to receive two novel monovalent oral type-2 poliovirus (OPV2) vaccine candidates in order to study the safety of the vaccines, the nature of viral shedding in participants, and the immunogenic effect of the vaccines. Investigators found that both OPV2 candidates increased the median blood titer of serum neutralizing antibodies, and all participants were seroprotected after vaccination. Severe events were reported in 40% of participants receiving candidate 1, and in 60% of participants receiving candidate 2; most events were increases in blood creatinine phosphokinase without accompanying clinical symptoms. There were no serious adverse events. In terms of shedding, 100% of participants receiving vaccine candidate 1 and 87% of participants receiving candidate 2 had vaccine virus detected in their stools. Viral shedding stopped after a median of 23 days (IQR 15-36 days) and 12 days (IQR 1-23) for candidates 1 and 2, respectively. Overall, the results from this study indicate an acceptable safety profile for the two vaccine candidates and a shedding rate that is not substantially increased compared to existing vaccines. As such, these candidates hold promise for future studies. Limitations for this study include the small sample size and the lack of placebo group.

Association of Cortical Stimulation–Induced Seizure With Surgical Outcome in Patients With Focal Drug-Resistant Epilepsy

Cortical stimulation during intracranial electroencephalography (EEG) is used in defining the epileptogenic zone in patients with epilepsy, with the aim of removing the seizure onset zone (SOZ). However, the effect of cortical stimulation on surgical outcomes has not been well studied. In this cohort study, investigators performed neurophysiologic characterization of stereo-electroencephalography (SEEG) data for 103 patients with focal drug-resistance epilepsy in order to examine the correlation between cortical stimulation findings with surgical outcomes. Investigators found that SEEG was able to induce at least 1 electroclinical seizure in 57.3% of patients, with a median response rate of 2 cortical stimulation-induced seizures per patient. The percentage of patients with a cortical stimulation-induced electroclinical seizure was 70.5% in the good outcome group and 47.5% in the poor outcome group (p=0.02). The results from this study indicate that patients who have cortical stimulation-induced typical electroclinical seizures have a higher likelihood of having a good surgical outcome than those without such induced seizures, and as such the inability to induce a cortical stimulation-induced seizure may prompt re-evaluation of surgical candidacy.

Assessment of the Safety of Pembrolizumab in Patients With HIV and Advanced Cancer—A Phase 1 Study

Immunotherapies such as anti-PD-1 (anti-programmed cell death 1) and anti-PD-L1 (anti-programmed cell death ligand 1) are effective in treating numerous malignancies. The safety and efficacy in patients who have both cancer and HIV, however, has not been well studied. In this non-randomized open-label trial, investigators treated 30 participants with advanced cancer and HIV with the anti-PD-1 monoclonal antibody pembrolizumab in order to study the safety and tolerability of the therapy. Patients with HIV were treated with anti-retroviral therapy and had a CD4+ T-cell count greater than 100 cells/μL. Investigators found that most adverse events at least possibly attributed to pembrolizumab were grade 1 or 2 (22 events), and 20% were grade 3 (6 events). One participant died after developing a polyclonal Kaposi sarcoma (KS) herpesvirus-associated B-cell lymphoproliferation; this participant had pretreatment KS herpesvirus. In terms of response to pembrolizumab, investigators found that half of the 30 patients had stable disease for less than 24 weeks, 1 patient had a complete response, 2 patients had a partial response, and 8 patients had progressive disease. The complete response was seen in a patient with lung cancer. Taken together, the results from this study suggest that pembrolizumab has acceptable safety in patients with both HIV and cancer, although KS herpesvirus-associated B-cell lymphoproliferation is a concern. This study was limited in its small sample size and its nonrandomized nature; more studies with patients with and without HIV are needed to gauge the effectiveness of pembrolizumab on treating cancer in patients with HIV compared to those without HIV.

Image-guided Irreversible Electroporation of Localized Prostate Cancer: Functional and Oncologic Outcomes

There is a need for focal therapies for low to intermediate-risk prostate cancers, as whole-gland therapies have many complications without necessarily providing a survival benefit. Irreversible electroporation (IRE), a nonthermal ablative method based on forming nanoscale defects in cell membranes, has been proposed as a possible treatment. In this cohort study, investigators conducted IRE on 30 men with prostate cancer in order to study the effect of IRE on treating prostate cancer as well as adverse effects. The patients in this study had an average PSA level of 8.65 ng/mL and a mean tumor size of 13.5 mm before treatment. After treatment, investigators found that the PSA level decreased to 2.35 ng/mL on average (IQR 1 to 3.4 ng/mL) at 12 months (p<0.001). The rate of treatment failure was 17.9% at 6 months as found through posttreatment biopsy. In terms of adverse events, leak-free and pad-free continence rate was 90% at baseline and 86.2% at 12 months (p>0.99), while the proportion of men with erection sufficient for penetration was 83.3% at baseline and 79.3% at 12 months (p>0.99). The results from this study indicate that IRE was associated with low urogenital risks and provided some efficacy for treating prostate cancer, although the 17.9% treatment failure rate requires workup. This study was limited in its small sample size and large attrition for follow up.

Diffusion Tensor MRI of White Matter of Healthy Full-term Newborns: Relationship to Neurodevelopmental Outcomes

Newborn babies have variations in white matter development, but it is unknown whether these variations are associated with changes in later neurodevelopment. In this prospective cohort study, investigators performed MRI examinations for 38 full-term infants at 2 weeks of age and then followed up at 2 years with the Bayley Scales of Infant Development (BSID) in order to examine any associations between white matter findings at 2 weeks and BSID scores at 2 years. Investigators found that tract-based spatial statistics (TBSS) analyses showed correlations (p<0.05) between fractional anisotropy (FA) values measured at 2 weeks and multiple BSID subscale scores at 2 years of age. Different white matter regions showed clusters with positive correlation between FA and scores for socioemotional, cognitive, language, and motor skills. Adaptive behavior scores and FA values had no correlation in any white mater regions, and there were no negative correlations between FA values and any BSID scores. In terms of covariates, investigators found that an infant’s gestational age at birth was an important confounding factor in FA-BSID relationships, with a trend of positive correlations between gestational age at birth and BSID scores (p=0.05, R =0.34 for cognitive scores). Different BSID scores correlated positively with mean FA values of different neurological structures. Taken together, the results from this study suggest that higher FA values and greater early white matter development is indicative of better later neurodevelopment, and that gestational age likely impacts both white matter development and neurodevelopmental outcomes. This study also provides some weak correlations between BSID scores and FA values of certain structures. This study is limited in a small sample size and inability to assess many other postnatal factors.

Image: PD

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