Interleaved Propofol-Ketamine Maintains DBS Physiology and Hemodynamic Stability: A Double-Blind Randomized Controlled Trial.

BACKGROUND: The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. Although it offers high-quality microelectrode recordings and therapeutic-window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy. OBJECTIVES: The aim is to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for the physiological testing phase of DBS surgery. METHODS: Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events. RESULTS: Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively. CONCLUSIONS: Ketamine-induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post-operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A phase 2 study of ibrutinib maintenance following first-line high-dose methotrexate-based chemotherapy for elderly patients with primary central nervous system lymphoma.

BACKGROUND: Elderly patients account for nearly 70% of all primary central nervous system lymphoma (PCNSL) cases. They cannot tolerate aggressive treatment and have poor prognosis with a median overall survival (OS) of less than 2 years and progression-free survival (PFS) of 6-16 months. Ibrutinib penetrates the blood-brain barrier and has shown activity in PCNSL. METHODS: This prospective study investigated whether ibrutinib maintenance is feasible, and whether it can benefit elderly PCNSL patients in terms of expected 2-year PFS. It is an open label, phase 2 study in newly diagnosed PCNSL patients 60-85 years old who responded to first-line high-dose methotrexate (HDMTX)-based treatment with partial or complete response. Ibrutinib maintenance (560 mg/d) was continued until disease progression or intolerable toxicity. RESULTS: Twenty patients were enrolled, with a median age of 72 years (range, 61-80). Median time on ibrutinib maintenance was 12.5 (range, 2-46) months. Twelve patients stopped treatment: five due to central nervous system relapse and seven due to adverse events that were mainly grade 2. Five patients died (25%) all due to relapse. The 1- and 2-year PFS are 90% and 72.6%, respectively, and the 2-year OS is 89%. CONCLUSIONS: The study reached its primary end points and also showed that ibrutinib maintenance is tolerated reasonably well by the elderly. Therefore, this study supports the concept that ibrutinib maintenance should be further evaluated as an optional consolidation measure in the elderly.

Psychosis, short stature in benign hereditary chorea: a novel thyroid transcription factor-1 mutation.

Benign hereditary chorea (BHC) is a rare autosomal dominant nonprogressive movement disorder. In some cases the phenotype includes, besides choreoathetosis, thyroid dysfunction and pulmonary infections in infancy, as expressed by the name "Brain-Thyroid-Lung syndrome". Mutations in the thyroid transcription factor-1 (TITF-1) gene have been identified in some BHC families. We present the phenotypic features of a family with chorea, hypothyroidism, and lung dysfunction. All affected individuals suffered from a nonprogressive chorea with infancy onset. All showed short stature and some webbed neck. One patient suffered from psychosis at the age of 27 years another from lung carcinoma. In all affected individuals, a novel mutation consisting of heterozygous C to A substitution at position 650 of the coding sequence of the TITF-1 gene, exon 3 was detected, leading to a premature stop at codon 217 (S217X). We describe the unique phenotypic features and intrafamilial variability expressing this novel mutation.

CD40 ligand expression correlates with resolution of peritonitis and mononuclear cell recruitment.

BACKGROUND: CD40 belongs to the tumor necrosis factor receptor family and its ligation is a central event in major inflammatory and immune reactions. We have previously demonstrated that CD40 ligation upregulates the secretion of mononuclear chemokines from peritoneal mesothelial cells (PMC), and that blocking the CD40 ligand (CD154) reduced the mononuclear infiltrate in a model of peritonitis. OBJECTIVE: To characterize the kinetics of CD154 expression on peritoneal Leukocytes and examine the correlation of this occurrence with the mononuclear transition at the resolution phase of peritonitis. METHODS: Leukocytes were collected from the effluent of 11 patients during episodes of peritonitis while undergoing peritoneal dialysis (PD). The effluent was then analyzed by flow cytometry to characterize CD154 expression. RESULTS: CD154 expression on peritoneal mononuclear cells gradually increased during the resolution phase of peritonitis, peaking first on T cells (CD4+ and CD8* cells at 20-45 hours) and then on macrophages (CD14' at 20-50 hours). The maximal expression of CD154 on macrophages, CD4* cells, and CD8* cells during peak hours reached values of 33% * 23%, 4%-3%, and 24%-17%, respectively. The increase in CD154 expression was in-negative correlation (r= -0.44, p = 0.032) with total Leukocyte numbers and in positive correlation (r = 0.52, p = 0.009) with the increase of mononuclear cells. Deterioration of peritonitis was associated with a decrease in CD154 levels, while recurrence of peritonitis was related to high CD154 Levels. CONCLUSION: Our data, which show a positive correlation between CD154 Levels and mononuclear dominance, suggest that CD40-CD154 Ligation plays an important role in the transition to mononuclear predominance in the late phase of peritonitis.