Is tissue still the issue? The promise of liquid biopsy in uveal melanoma

Uveal melanoma (UM) is the second most frequent type of melanoma. Therapeutic options for UM favor minimally invasive techniques such as irradiation for vision preservation. As a consequence, no tumor material is obtained. Without available tissue, molecular analyses for gene expression, mutation or copy number analysis cannot be performed. Thus, proper patient stratification is impossible and patients\u27 uncertainty about their prognosis rises. Minimally invasive techniques have been studied for prognostication in UM. Blood-based biomarker analysis has become more common in recent years; however, no clinically standardized protocol exists. This review summarizes insights in biomarker analysis, addressing new insights in circulating tumor cells, circulating tumor DNA, extracellular vesicles, proteomics, and metabolomics. Additionally, medical imaging can play a significant role in staging, surveillance, and prognostication of UM and is addressed in this review. We propose that combining multiple minimally invasive modalities using tumor biomarkers should be the way forward and warrant more attention in the coming years

Genetics of ocular melanoma: Insights into genetics, inheritance and testing

Ocular melanoma consists of posterior uveal melanoma, iris melanoma and conjunctival melanoma. T

Acute posthypoxic myoclonus after cardiopulmonary resuscitation

<p>Abstract</p> <p>Background</p> <p>Acute posthypoxic myoclonus (PHM) can occur in patients admitted after cardiopulmonary resuscitation (CPR) and is considered to have a poor prognosis. The origin can be cortical and/or subcortical and this might be an important determinant for treatment options and prognosis. The aim of the study was to investigate whether acute PHM originates from cortical or subcortical structures, using somatosensory evoked potential (SEP) and electroencephalogram (EEG).</p> <p>Methods</p> <p>Patients with acute PHM (focal myoclonus or status myoclonus) within 72 hours after CPR were retrospectively selected from a multicenter cohort study. All patients were treated with hypothermia. Criteria for cortical origin of the myoclonus were: giant SEP potentials; or epileptic activity, status epilepticus, or generalized periodic discharges on the EEG (no back-averaging was used). Good outcome was defined as good recovery or moderate disability after 6 months.</p> <p>Results</p> <p>Acute PHM was reported in 79/391 patients (20%). SEPs were available in 51/79 patients and in 27 of them (53%) N20 potentials were present. Giant potentials were seen in 3 patients. EEGs were available in 36/79 patients with 23/36 (64%) patients fulfilling criteria for a cortical origin. Nine patients (12%) had a good outcome. A broad variety of drugs was used for treatment.</p> <p>Conclusions</p> <p>The results of this study show that acute PHM originates from subcortical, as well as cortical structures. Outcome of patients admitted after CPR who develop acute PHM in this cohort was better than previously reported in literature. The broad variety of drugs used for treatment shows the existing uncertainty about optimal treatment.</p

Combined and Sequential Treatment with Deep Brain Stimulation and Continuous Intrajejunal Levodopa Infusion for Parkinson’s Disease

(1) Background: Deep brain stimulation (DBS) and continuous intrajejunal levodopa infusion (CLI) are efficacious treatments of medication related motor response fluctuations in advanced Parkinson’s disease (PD). Literature regarding the use of both advanced treatments within one patient is scarce. (2) Methods: We present a retrospective single center case series and a review of the literature. Patients with PD who were treated with both DBS and CLI in our tertiary referral center between 2005 and 2020 were identified and medical records were assessed. Additionally, literature on patients treated with both therapies was systematically searched for in Medline and Embase. (3) Results: Nineteen patients were included. Medication related motor response fluctuations were a major indication for the second therapy in all but one. Of nine patients initially treated with DBS, five reported improvement with CLI. Seven of ten patients initially treated with CLI experienced benefits from DBS. The systematic literature search resulted in fifteen previous publications comprising 66 patients. Of the 59 patients, for whom the effect of the second treatment was known, 57 improved. (4) Conclusions: PD patients, who have persisting medication related motor response fluctuations, despite DBS or CLI treatment, may benefit from an additional or alternative treatment with either CLI or DBS

Genetics of ocular melanoma: Insights into genetics, inheritance and testing

Ocular melanoma consists of posterior uveal melanoma, iris melanoma and conjunctival melanoma. These malignancies derive from melanocytes in the uveal tract or conjunctiva. The genetic profiles of these different entities differ from each other. In uveal melanoma, GNAQ and GNA11 gene mutations are frequently found and prognosis is based on mutation status of BAP1, SF3B1 and EIF1AX genes. Iris melanoma, also originating from the uvea, has similarities to the genetic makeups of both posterior uveal melanoma (UM) and conjunctival melanoma since mutations in GNAQ and GNA11 are less common and genes involved in conjunctival melanoma such as BRAF have been described. The genetic spectrum of conjunctival melanoma, however, includes frequent mutations in the BRAF, NRAS and TERT promoter genes, which are found in cutaneous melanoma as well. The BRAF status of the tumor is not correlated to prognosis, whereas the TERT promoter gene mutations are. Clinical presentation, histopathological characteristics and copy number alterations are associated with survival in ocular melanoma. Tissue material is needed to classify ocular melanoma in the different subgroups, which creates a need for the use of noninvasive techniques to prognosticate patients who underwent eye preserving treatment

Botulinum neurotoxin treatment in jerky and tremulous functional movement disorders: a double-blind, randomised placebo-controlled trial with an open-label extension

Objective: To study the effect of botulinum neurotoxin (BoNT) treatment in jerky and tremulous functional movement disorders (FMD). Methods: Patients with invalidating, chronic (>1 year) symptoms were randomly assigned to two subsequent treatments with BoNT or placebo every 3 months with stratification according to symptom localisation. Improvement on the dichotomised Clinical Global Impression-Improvement scale (CGI-I) (improvement vs no change or worsening) at 4 months, assessed by investigators blinded to the allocated treatment was the primary outcome. Subsequently all patients were treated with BoNT in a ten month open-label phase. Results: Between January 2011 and February 2015 a total of 239 patients were screened for eligibility of whom 48 patients were included. No difference was found on the primary outcome (BoNT 16 of 25 (64.0%) vs Placebo 13 of 23 patients (56.5%); proportional difference 0.075 (95% CI -0.189 to 0.327; p=0.77). Secondary outcomes (symptom severity, disease burden, disability, quality of life and psychiatric symptoms) showed no between-group differences. The open-label phase showed improvement on the CGI-I in 19/43 (44.2%) of remaining patients, with a total of 35/43 (81.4%) improvement compared with baseline. Conclusions: In this double-blind randomised controlled trial of BoNT for chronic jerky and tremulous FMD, we found no evidence of improved outcomes compared with placebo. Motor symptoms improved in a large proportion in both groups which was sustained in the open-label phase. This study underlines the substantial potential of chronic jerky and tremulous FMD patients to recover and may stimulate further exploration of placebo-therapies in these patients