One patient for whom an MR-guided focused ultrasound (MRgFUS) pallidotomy was attempted was discovered to have multiple new skull lesions with the appearance of infarcts on the MRI scan 3 months ...after his attempted treatment. The authors conducted a retrospective review of the first 30 patients treated with MRgFUS to determine the incidence of skull lesions in patients undergoing these procedures and to consider possible causes.
A retrospective review of the MRI scans of the first 30 patients, 1 attempted pallidotomy and 29 ventral intermediate nucleus thalamotomies, was conducted. The correlation of the mean skull density ratio (SDR) and the maximum energy applied in the production or attempted production of a brain lesion was examined.
Of 30 patients treated with MRgFUS for movement disorders, 7 were found to have new skull lesions that were not present prior to treatment and not visible on the posttreatment day 1 MRI scan. Discomfort was reported at the time of treatment by some patients with and without skull lesions. All patients with skull lesions were completely asymptomatic. There was no correlation between the mean SDR and the presence or absence of skull lesions, but the maximum energy applied with the Exablate system was significantly greater in patients with skull lesions than in those without.
It is known that local skull density, thickness, and SDR vary from location to location. Sufficient energy transfer resulting in local heating sufficient to produce a bone lesion may occur in regions of low SDR. A correlation of lesion location and local skull properties should be made in future studies.
To outline features of the neurologic examination that can be performed virtually through telemedicine platforms (the virtual neurological examination VNE), and provide guidance for rapidly pivoting ...in-person clinical assessments to virtual visits during the COVID-19 pandemic and beyond.
The full neurologic examination is described with attention to components that can be performed virtually.
A screening VNE is outlined that can be performed on a wide variety of patients, along with detailed descriptions of virtual examination maneuvers for specific scenarios (cognitive testing, neuromuscular and movement disorder examinations).
During the COVID-19 pandemic, rapid adoption of virtual medicine will be critical to provide ongoing and timely neurological care. Familiarity and mastery of a VNE will be critical for neurologists, and this article outlines a practical approach to implementation.
Abstract
Background
Nasopharyngeal specimens (NPS) are commonly used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing but can be uncomfortable for patients. Self-collected ...saliva specimens (SS) or anterior nasal specimens (ANS) for SARS-CoV-2 detection are less invasive, but the sensitivity of these specimen types has not been thoroughly evaluated.
Methods
During September–November 2020, 730 adults undergoing SARS-CoV-2 testing at community testing events and homeless shelters in Denver provided self-collected SS and ANS before NPS collection and answered a short survey about symptoms and specimen preference. Specimens were tested for SARS-CoV-2 by means of real-time reverse-transcription polymerase chain reaction (rRT-PCR); viral culture was performed on a subset of specimens positive by rRT-PCR. The sensitivity of SS and ANS for SARS-CoV-2 detection by rRT-PCR was measured against that of NPS. Subgroup analyses included test outcomes by symptom status and culture results.
Results
Sensitivity for SARS-CoV-2 detection by rRT-PCR appeared higher for SS than for ANS (85% vs 80%) and higher among symptomatic participants than among those without symptoms (94% vs 29% for SS; 87% vs 50% for ANS). Among participants with culture-positive SARS-CoV-2 by any specimen type, the sensitivities of SS and ANS by rRT-PCR were 94% and 100%, respectively. SS and ANS were equally preferred by participants; most would undergo NPS collection again despite this method’s being the least preferred.
Conclusions
SS were slightly more sensitive than ANS for SARS-CoV-2 detection with rRT-PCR. With both SS and ANS, SARS-CoV-2 was reliably detected among participants with symptoms. Self-collected SS and ANS offer practical advantages, are preferred by patients, and might be most useful for testing people with coronavirus disease 2019 symptoms.
Viral fusion is a critical step in the entry pathway of enveloped viruses and remains a viable target for antiviral exploration. The current approaches for studying fusion mechanisms include ensemble ...fusion assays, high-resolution cryo-TEM, and single-molecule fluorescence-based methods. While these methods have provided invaluable insights into the dynamic events underlying fusion processes, they come with their own limitations. These often include extensive data and image analysis in addition to experimental time and technical requirements. This work proposes the use of the spin–spin T2 relaxation technique as a sensitive bioanalytical method for the rapid quantification of interactions between viral fusion proteins and lipids in real time. In this study, new liposome-coated iron oxide nanosensors (LIONs), which mimic as magnetic-labeled host membranes, are reported to detect minute interactions occurring between the membrane and influenza’s fusion glycoprotein, hemagglutinin (HA). The influenza fusion protein’s interaction with the LION membrane is detected by measuring changes in the sensitive spin–spin T2 magnetic relaxation time using a bench-top NMR instrument. More data is gleaned from including the fluorescent dye DiI into the LION membrane. In addition, the effects of environmental factors on protein–lipid interaction that affect fusion such as pH, time of incubation, trypsin, and cholesterol were also examined. Furthermore, the efficacy and sensitivity of the spin–spin T2 relaxation assay in quantifying similar protein/lipid interactions with more native configurations of HA were demonstrated using virus-like particles (VLPs). Shorter domains derived from HA were used to start a reductionist path to identify the parts of HA responsible for the NMR changes observed. Finally, the known fusion inhibitor Arbidol was employed in our spin–spin T2 relaxation-based fusion assay to demonstrate the application of LIONs in real-time monitoring of this aspect of fusion for evaluation of potential fusion inhibitors.
Summary Background Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we ...assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose (18 FFDG)-PET correlate with clinical outcome. Methods Patients with advanced measurable BTCs were given the following treatment on days 1 and 15 of a 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m2 (10 mg/m2 per min) and oxaliplatin 85 mg/m2 (2-h infusion). 18 FFDG-PET scans were obtained at baseline and after completion of the second cycle. The primary endpoint was progression-free survival (PFS). Efficacy and safety analyses were by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00361231. Findings 35 patients were enrolled and evaluable for efficacy and toxicity. Median PFS was 7·0 months (95% CI 5·3–10·3), and PFS at 6 months was 63% (47–79), which was below the targeted rate of 70%. Grade 3–4 toxic effects included neutropenia (n=7), raised alanine aminotransferase concentrations (n=5), peripheral neuropathy (n=5), and hypertension (n=5). 18 FFDG-PET scans showed a significant decrease in maximum standardised uptake value (SUVmax ) after two cycles of treatment (5·72 SD 2·01 at baseline; 3·73 SD 1·88 after two cycles; p<0·0001). These changes were more pronounced in patients with partial response or stable disease than those with progressive disease (24 patients, −2·80 SD 1·95 vs five patients, 1·41 SD 3·13; p=0·009). Change in SUVmax was a significant predictor of PFS (HR 1·35, 1·14–1·60, p=0·0006) and overall survival (1·25, 1·05–1·50, p=0·01). Interpretation GEMOX-B showed antitumour activity with tolerable safety in patients with advanced BTCs. Decreases in SUVmax on 18 FFDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival. Funding Genentech Oncology and Sanofi-Aventis.
To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma ...(PDAC) patients.
Patients with radiographically resectable, biopsy-proven PDAC were treated with neoadjuvant short-course (2-week) proton-based radiation with capecitabine, followed by surgery and adjuvant gemcitabine. The primary objective was to demonstrate a rate of toxicity grade ≥ 3 of <20%. Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood.
The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled, of whom 35 patients were treated in the phase 2 portion. There were no grade 4 or 5 toxicities, and only 2 of 35 patients (4.1%) experienced a grade 3 toxicity event (chest wall pain grade 1, colitis grade 1). Of 48 patients eligible for analysis, 37 underwent pancreaticoduodenectomy. Thirty of 37 (81%) had positive nodes. Locoregional failure occurred in 6 of 37 resected patients (16.2%), and distant recurrence occurred in 35 of 48 patients (72.9%). With median follow-up of 38 months, the median progression-free survival for the entire group was 10 months, and overall survival was 17 months. Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12, stromal CXCR7 expression, and circulating biomarkers CEA, CA19-9, and HGF (all, P<.05).
This study met the primary endpoint by showing a rate of 4.1% grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation. Treatment was associated with favorable local control. In exploratory analyses, KRAS(G12D) status and high CXCR7 expression and circulating CEA, CA19-9, and HGF levels were associated with poor survival.
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