Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

Metastatic stage vs complications at radical nephrectomy with inferior vena cava thrombectomy

BackgroundTo investigate perioperative complication rates at radical nephrectomy (RN) according to inferior vena cava thrombectomy (IVC-T) status and stage (metastatic vs non-metastatic) within kidney cancer patients.Materials and methodsWe ascertained perioperative complication rates within the National Inpatient Sample database (2016–2019). First, log-link linear Generalized Estimating Equation function (GEE) regression models (adjusted for hospital clustering and weighted for discharge disposition) tested complication rates in IVC-T patients, according to metastatic stage. Subsequently, a subgroup analysis relied on RN patients with or without IVC-T. Here, multivariable logistic regression models tested complication rates in RN patients according to IVC-T status, after propensity score matching including metastatic stage.ResultsOf 26,299 RN patients, 461 (2%) patients underwent IVC-T. Of those, 252 (55%) were non-metastatic vs 209 (45%) were metastatic. Rates of acute kidney injury (AKI), transfusion, cardiac, thromboembolic and other medical complications in non-metastatic vs metastatic patients were 40 vs 40%, 25 vs 22%, 21 vs 23%, 19 vs 14% and 38 vs 40%, respectively (all p ≥ 0.2). Metastatic stage in IVC-T patients did not predict differences in complications in log-link linear GEE regression models (all p > 0.1). However, in logistic regression models with propensity score matching, relying on the overall cohort of RN patients, IVC-T status was associated with higher complication rates (all p < 0.001): AKI (Odds ratio [OR]:2.60; 95%-CI [95%-Confidence interval: 1.97–3.44), transfusions (OR:2.40; 95%-CI: 1.72–3.36), cardiac (OR:2.27; 95%-CI: 1.49–3.47), thromboembolic (OR:9.07; 95%-CI: 5.21–16.58) and other medical complications (OR:2.01; 95%-CI: 1.52–2.66).ConclusionsThe current analyses indicate that presence of concomitant IVC-T is associated with higher complication rate at RN. Conversely, metastatic stage has no effect on recorded complication rates.     

Connectivity measures suggest a sub-cortical generator of myoclonus in Angelman syndrome

ObjectiveThe clinical and neurophysiological characteristics of myoclonus in Angelman syndrome (AS) have been evaluated in single case or small cohorts, with contrasting results. We evaluated the features of myoclonus in a wide cohort of AS patients.MethodsWe performed polygraphic EEG-EMG recording in 24 patients with genetically confirmed AS and myoclonus. Neurophysiological investigations included jerk-locked back-averaging (JLBA), cortico-muscular coherence (CMC) and generalised partial directed coherence (GPDC). CMC and GPDC analyses were compared to those obtained from 10 healthy controls (HC).ResultsTwenty-four patients (aged 3–35 years, median 20) were evaluated. Sequences of quasi-continuous rhythmic jerks mostly occurred at alpha frequency or just below (mean 8.4 ± 1.4 Hz), without EEG correlate. JLBA did not show any clear transient preceding the jerks. CMC showed bilateral over-threshold CMC in alpha band that was prominent on the contralateral hemisphere in the patient group as compared to HC group. GPDC showed a significantly higher alpha outflow from both hemispheres toward activated muscles in the patient group, and a significantly higher beta outflow from contralateral hemisphere in the HC group.ConclusionsThese neurophysiological findings suggest a subcortical generator of myoclonus in AS.SignificanceMyoclonus in AS has not a cortical origin as previously hypothesised.     

Spondylodiscitis after transoral robotic surgery: Retrospective 7-case series from the GETTEC group

BackgroundCervical spondylodiscitis is a rare but severe complication of pharyngeal surgery.Material and methodsThis multicenter retrospective study reported all patients in the database of the French head and neck tumor study group (GETTEC) affected by cervical spondylodiscitis after transoral robotic surgery (TORS) for malignant pharyngeal tumor from January 2010 to January 2017.ObjectivesTo describe cases of post-TORS cervical spondylodiscitis, identify alarm signs, and determine optimal management of these potentially lethal complications.ResultsSeven patients from 6 centers were included. Carcinomas were located in the posterior pharyngeal wall. Tumor stage was T1 or T2. All patients had risk factors for spondylodiscitis. Mean time to diagnosis was 12.6 days. The interval between surgery and spondylodiscitis diagnosis ranged from 20 days to 4.5 months, for a mean 2.1 months. The most common symptom was neck pain (87%). Infections were polymicrobial; micro-organisms were isolated in 5 cases and managed by intravenous antibiotics, associated to medullary decompression surgery in 3 cases. Follow-up found favorable progression in 4 cases, and 3 deaths (mortality, 43%).ConclusionThis French multicenter study found elevated mortality in post-TORS spondylodiscitis, even in case of limited resection. Surgeons must be aware of this complication and alerted by persistent neck pain, fever, asthenia, impaired or delayed posterior pharyngeal wall wound healing or elevation of inflammatory markers. MRI is the most effective diagnostic radiological examination.     

Evaluation of vilazodone for the treatment of depressive and anxiety disorders

Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.

Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.

Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD.