Thrombus Distribution in Vaccine-induced Immune Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination.

Vaccination strategies have been at the forefront of controlling the COVID-19 pandemic. An association between vaccine-induced immune thrombotic thrombocytopenia (VITT) and one of these vaccines, the ChAdOx1 nCov-19 vaccine, is now recognized. The purpose of this study was to investigate the frequency and location of thrombosis in each vascular system using CT, MRI, and US to identify additional sites of thrombus in a United Kingdom-wide sample of patients with confirmed VITT. Thirty-two radiology centers identified through the national collaborative Radiology Academic Network for Trainees were invited from the United Kingdom; seven of these contributed to this study. All patients with confirmed VITT ¬between February 3 and May 12, 2021, who met the inclusion criteria were included. The location and extent of thrombi were evaluated using CT, MRI, and US. A total of 40 patients (median age, 41 years [IQR, 32-52]; 22 [55%] men) with confirmed vaccine-induced immune thrombotic thrombocytopenia after administration of their first ChAdOx1 nCov-19 vaccine were included. Thirty-two patients (80%) developed symptoms within the first 14 days, and eight (20%) developed symptoms within 14-28 days. Twenty-nine patients (72%) experienced neurologic symptoms and were confirmed to have cerebral venous sinus thrombosis, 12 (30%) had clinical deterioration and repeat imaging demonstrated extension of their primary thrombus, and eight (20%) died. Twenty-five of 30 patients (83%) who underwent additional imaging had occult thrombosis. In conclusion, patients with VITT are likely to have multiple sites of thrombosis, with the most frequent being cerebral venous sinus thrombosis in combination with pulmonary embolism and portomesenteric venous thrombosis. Whole-body imaging with contrast-enhanced CT can be used to identify occult thrombosis.

Management of massive splenomegaly.

A case demonstrating diagnostic and therapeutic rational for surgical management of massive splenomegaly.

Huntingtin-lowering strategies for Huntington's disease.

INTRODUCTION: Huntington's disease (HD) is an incurable, autosomal dominant neurodegenerative disease caused by an abnormally long polyglutamine tract in the huntingtin protein. Because this mutation causes disease via gain-of-function, lowering huntingtin levels represents a rational therapeutic strategy. AREAS COVERED: We searched MEDLINE, CENTRAL, and other trial databases, and relevant company and HD funding websites for press releases until April 2020 to review strategies for huntingtin lowering, including autophagy and PROTACs, which have been studied in preclinical models. We focussed our analyses on oligonucleotide (ASOs) and miRNA approaches, which have entered or are about to enter clinical trials. EXPERT OPINION: ASO and mRNA approaches for lowering mutant huntingtin protein production and strategies for increasing mutant huntingtin clearance are attractive because they target the cause of disease. However, questions concerning the optimal mode of delivery and associated safety issues remain. It is unclear if the human CNS coverage with intrathecal or intraparenchymal delivery will be sufficient for efficacy. The extent that one must lower mutant huntingtin levels for it to be therapeutic is uncertain and the extent to which CNS lowering of wild-type huntingtin is safe is unclear. Polypharmacy may be an effective approach for ameliorating signs and symptoms and for preventing/delaying onset and progression.

Influence of Obesity on Complications, Clinical Outcome, and Subsidence After Anterior Lumbar Interbody Fusion (ALIF): Prospective Observational Study.

BACKGROUND: The complications associated with obesity have been well described for posterior lumbar spinal surgery. However, the influence of obesity on anterior lumbar interbody fusion (ALIF) is not well established. We aimed to compare complication risks, functional outcomes, and subsidence rates in normal-weight, overweight, and obese patients who underwent ALIF. METHODS: A total of 137 consecutive patients undergoing ALIF surgery from 2012 to 2014 were followed prospectively. Patients were categorized into 3 groups according to their body mass index (BMI). Patients were evaluated preoperative and postoperatively. Outcome measures included Short Form-12, Oswestry Disability Index, surgical complications, and subsidence. RESULTS: There was no significant difference between the BMI groups in terms of baseline age, proportion of men, levels operated, smoking status, diabetes status, or anterior, posterior, or average disc height. There was no difference in operative duration, blood loss, or hospital stay. At 12-month follow-up, no difference was found in terms of total complications, change in Short Form-12 mental or physical component scores, or Oswestry Disability Index scores. Average disc height was significant lower for the obese group (11.3 mm) compared with the normal-weight (14.4 mm) group. Fusion rate was also significantly lower for patients who were obese (60%) compared with normal-weight (88.2%) and overweight patients (76%) (P = 0.014). Delayed subsidence rates also were similar between normal-weight and overweight patients. CONCLUSIONS: There were no differences in functional outcomes or complications in patients with elevated BMI compared with normal-weight patients. Fusion rates were lower for patients were obese. Obesity should not be considered a contraindication to surgery in patients with appropriate indication to undergo ALIF.

Insights into the mechanisms of deep brain stimulation.

Despite long-term and widespread use of deep brain stimulation (DBS) in a variety of neurological conditions, the underlying mechanisms of action have been elusive. Growing evidence suggests that DBS acts through multimodal mechanisms that are not limited to inhibition and excitation of basal ganglia circuits. DBS also seems to act over variable time spans - for example, the effects on tremor are immediate, whereas the effects on dystonia emerge over several weeks - suggesting that large networks are targeted. Studies reviewing the use of DBS in pain and obsessive-compulsive disorder have demonstrated direct involvement of axonal fibres rather than grey matter. In this Review, we draw on clinical and experimental data to examine the various hypotheses that have been put forward to explain the effects of DBS. In agreement with several other experts, we suggest that the term 'deep brain stimulation' warrants modification. A potentially more accurate term is 'deep brain neuromodulation', as the mode of action spans an array of therapeutic effects over a variable period of time, and is not just limited to 'stimulation' of the basal ganglia brain centres. Terms such as 'electrical neuro-network modulation' may be useful for applications in which deep brain structures are not the primary target.