Tumor Immune Microenvironment in Gynecologic Cancers.

Gynecologic cancers have varying response rates to immunotherapy due to the heterogeneity of each cancer's molecular biology and features of the tumor immune microenvironment (TIME). This article reviews key features of the TIME and its role in the pathophysiology and treatment of ovarian, endometrial, cervical, vulvar, and vaginal cancer. Knowledge of the role of the TIME in gynecologic cancers has been rapidly developing with a large body of preclinical studies demonstrating an intricate yet dichotomous role that the immune system plays in either supporting the growth of cancer or opposing it and facilitating effective treatment. Many targets and therapeutics have been identified including cytokines, antibodies, small molecules, vaccines, adoptive cell therapy, and bacterial-based therapies but most efforts in gynecologic cancers to utilize them have not been effective. However, with the development of immune checkpoint inhibitors, we have started to see the rapid and successful employment of therapeutics in cervical and endometrial cancer. There remain many challenges in utilizing the TIME, particularly in ovarian cancer, and further studies are needed to identify and validate efficacious therapeutics.

Noninvasive brain stimulation for persistent postconcussion symptoms in mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is typically followed by various postconcussive symptoms (PCS), including headache, depression, and cognitive deficits. In 15-25% of cases, PCS persists beyond the usual 3-month recovery period, interfering with activities of daily living and responding poorly to pharmacotherapy. We tested the safety, tolerability, and efficacy of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) for alleviating PCS. Fifteen eligible patients with mTBI and PCS > 3 months postinjury consented to 20 sessions of rTMS (20 × 5-sec trains; 10 Hz at 110% threshold), with clinical and functional magnetic resonance imaging (fMRI) assessments before and after intervention and clinical assessment at 3-month follow-up. Primary outcomes were tolerability, safety, and efficacy, as measured with the PCS Scale. Secondary outcomes included the Cognitive Symptoms Questionnaire, neuropsychological test performance, and working memory task-associated activity as assessed with fMRI. Twelve patients completed all sessions. Three withdrew because of worsening symptoms or for an unrelated event. Stimulation intensity was increased gradually across sessions, and all subjects tolerated the protocol by the sixth session. Commonly reported side effects among completers were increased headache (n = 3) and greater sleep disturbance (n = 3). Participants also reported positive outcomes such as less sleep disturbance (n = 3), and better mental focus (n = 3). On average, PCS scores declined by 14.6 points (p = 0.009) and fMRI task-related activation peaks in the DLPFC increased after rTMS. rTMS is safe, tolerated by most patients with mTBI, and associated with both a reduction in severity of PCS and an increase in task-related activations in DLPFC. Assessment of this intervention in a randomized, control trial is warranted.

A measure of acoustic noise generated from transcranial magnetic stimulation coils.

The intensity of sound emanating from the discharge of magnetic coils used in repetitive transcranial magnetic stimulation (rTMS) can potentially cause acoustic trauma. Per Occupational Safety and Health Administration (OSHA) standards for safety of noise exposure, hearing protection is recommended beyond restricted levels of noise and time limits. We measured the sound pressure levels (SPLs) from four rTMS coils with the goal of assessing if the acoustic artifact levels are of sufficient amplitude to warrant protection from acoustic trauma per OSHA standards. We studied the SPLs at two frequencies (5 and 10 Hz), three machine outputs (MO) (60, 80 and 100%), and two distances from the coil (5 and 10 cm). We found that the SPLs were louder at closer proximity from the coil and directly dependent on the MO. We also found that in all studied conditions, SPLs were lower than the OSHA permissible thresholds for short (<15 min) acoustic exposure, but at extremes of use, may generate sufficient noise to warrant ear protection with prolonged (>8 h) exposure.

Outcomes of vagal nerve stimulation in a pediatric population: a single center experience.

OBJECTIVE: To evaluate the efficacy of vagus nerve stimulation (VNS) in pediatric patients with medically refractory epilepsy. METHOD: We reviewed the medical records of 252 consecutive patients who underwent VNS implantation at a single center over a 5-year period. Patients with complete 6- and 12-month follow-up data were included. Analysis was also done across various subgroups including gender, age at implantation, seizure type, abnormal MRI findings pre-implantation, number of medications at baseline, history of SE, and duration of epilepsy. RESULTS: Complete follow-up data were available for 69 patients. Median seizure reduction for these patients was 50% (Q1: 0%; Q3: 73%) at 6 months and 40% (Q1: -25%; Q3: 75%) at 12 months. When stratified by baseline seizure frequency, there was a significant reduction from baseline of 61% at 6 months and 69% at 12 months for patients in the high-baseline frequency group. There were no significant reductions at month 6 or 12 months for the lower-baseline frequency group. Adverse events were reported in 40.6% (28 out of 69 patients). Six patients had the VNS removed for reasons including lack of efficacy and side effects and were excluded from the study group. CONCLUSION: VNS provides significant seizure reduction, in particular in pediatric patients with a higher baseline seizure frequency.