Background:
Postoperative multiple sclerosis (MS) relapses are a concern among patients and providers.
Objective:
To determine whether MS relapse risk is higher postoperatively.
Methods:
Data were ...extracted from medical records of MS patients undergoing surgery at a tertiary center (2000–2016). Conditional logistic regression estimated within-patient unadjusted and age-adjusted odds of postoperative versus preoperative relapse.
Results:
Among 281 patients and 609 surgeries, 12 postoperative relapses were identified. The odds of postoperative versus preoperative relapse in unadjusted (odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.18–1.79; p = 0.33) or age-adjusted models (OR = 0.66, 95% CI = 0.20–2.16; p = 0.49) were not increased.
Conclusions:
Surgery/anesthesia exposure did not increase postoperative relapse risk. These findings require confirmation in larger studies.
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Background: Oncology patients are high users of the emergency department (ED), which often results in hospital admissions for management of cancer symptoms or cancer treatment toxicities. ...Interventions such as urgent care (UC) models can decrease such visits, and help improve patient management, health care utilization, and patient experience. Sunnybrook Health Sciences Centre, a large tertiary care hospital in Toronto, Canada has a high volume of medical oncology ED visits (average 4 per day) with about 50% admitted for management. Methods: A novel physician-assistant (PA) led and physician supervised UC model was developed to assist in medical oncology patient phone triage, assessment, and management of cancer or treatment related issues that would otherwise have been sent to the ED by the oncology team. There were two phases: 1) due to COVID, the patients were managed in a dedicated stream primarily using space and nursing in the ED, 2) a dedicated UC clinic with nursing support was opened for these patients. Results: In phase 1, there were 424 referrals over 24 months; 84% would have otherwise been sent through the usual ED process. 26% of patients were managed with PA navigation outside the UC program in other hospital settings. Of the 204 patients formally treated in the UC stream, 67.7% were discharged home. At 48 hours, 89% of discharged patients were stable or improved; this was 80% at 14 days, and 17.3% came back to the ED or were admitted within 14 days of the UC visit. In phase 2, there have so far been 214 referrals over 5 months; 83.6% would have otherwise been sent to the ED. Of the patients who were assessed, 77.9% were discharged home. Outcomes of these patients are being collected. The top 3 patient issues managed during both phases were: fever, pain, and dyspnea. Fifteen patient telephone surveys were completed, and 93.3% were either satisfied or highly satisfied with their UC experience. Conclusions: A novel PA-led triage and management model for urgent medical oncology patient issues was found in initial phase to be feasible and effective with streamlined care through the ED. Once a dedicated UC clinic was opened, referral volumes increased, and a high rate of ED diversion, patient discharge, and effective care was continued. Patients were also highly satisfied. Several ongoing process and outcome measures are being evaluated to help expand the scope and impact of this resource.
Next-generation sequencing (NGS) techniques are well-established for studying bacterial communities but not yet for microbial eukaryotes. Parasite communities remain poorly studied, due in part to ...the lack of reliable and accessible molecular methods to analyse eukaryotic communities. We aimed to develop and evaluate a methodology to analyse communities of the protozoan parasite Eimeria from populations of the Australian marsupial Petrogale penicillata (brush-tailed rock-wallaby) using NGS. An oocyst purification method for small sample sizes and polymerase chain reaction (PCR) protocol for the 18S rRNA locus targeting Eimeria was developed and optimised prior to sequencing on the Illumina MiSeq platform. A data analysis approach was developed by modifying methods from bacterial metagenomics and utilising existing Eimeria sequences in GenBank. Operational taxonomic unit (OTU) assignment at a high similarity threshold (97%) was more accurate at assigning Eimeria contigs into Eimeria OTUs but at a lower threshold (95%) there was greater resolution between OTU consensus sequences. The assessment of two amplification PCR methods prior to Illumina MiSeq, single and nested PCR, determined that single PCR was more sensitive to Eimeria as more Eimeria OTUs were detected in single amplicons. We have developed a simple and cost-effective approach to a data analysis pipeline for community analysis of eukaryotic organisms using Eimeria communities as a model. The pipeline provides a basis for evaluation using other eukaryotic organisms and potential for diverse community analysis studies.
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•Eimeria communities have not yet been analysed using next-generation sequencing.•We aimed to develop a sensitive and accurate methodology for data analysis of NGS.•Single PCR method was more sensitive to Eimeria than nested PCR.•The 97% similarity threshold was more accurate but 95% had greater resolution.•The methodology can be adjusted for genetic community analysis of other eukaryotes.
•The impact of known crocodilian skin pathogens including viral, bacterial, fungal and helminth taxa are reviewed.•Best husbandry practices to minimise these pathogens are discussed.•Husbandry ...improvements, such as heating, have already seen a reduced incidence in many of these pathogens.•Viral pathogens are the largest risk to crocodilian skin quality and require more than improved husbandry practices.
The control of pathogens that target crocodilian skin is essential to the long-term success and sustainability of intensive farming operations worldwide. To understand the impact these pathogens may have on the skin, a brief overview of skin histology is given. A review of the known viral, bacterial, fungal and helminth taxa associated with skin conditions in commercially significant crocodilian species is presented. Best management practices are discussed, with an emphasis on addressing extrinsic factors that influence transmission and pathogenicity. It is argued that, in the past, reduced immune function arising from inadequate thermal regulation was the leading cause of skin disease in captive crocodilians. Consequently, innovations such as temperature control, coupled with the adoption of more stringent hygiene standards, have greatly reduced the prevalence of many infectious skin conditions in intensively farmed populations. However, despite improvements in animal husbandry and disease management, viral pathogens such as West Nile virus, herpesvirus and poxvirus continue to afflict crocodilians in modern captive production systems.
OBJECTIVETo identify the rate of change of clinical outcome measures in children with 2 types of congenital muscular dystrophy (CMD), COL6-related dystrophies (COL6-RDs) and LAMA2-related dystrophies ...(LAMA2-RDs).
METHODSOver the course of 4 years, 47 individuals (23 with COL6-RD and 24 with LAMA2-RD) 4 to 22 years of age were evaluated. Assessments included the Motor Function Measure 32 (MFM32), myometry (knee flexors and extensors, elbow flexors and extensors), goniometry (knee and elbow extension), pulmonary function tests, and quality-of-life measures. Separate linear mixed-effects models were fitted for each outcome measurement, with subject-specific random intercepts.
RESULTSTotal MFM32 scores for COL6-RDs and LAMA2-RDs decreased at a rate of 4.01 and 2.60 points, respectively, each year (p < 0.01). All muscle groups except elbow flexors for individuals with COL6-RDs decreased in strength between 1.70% (p < 0.05) and 2.55% (p < 0.01). Range-of-motion measurements decreased by 3.21° (p < 0.05) at the left elbow each year in individuals with LAMA2-RDs and 2.35° (p < 0.01) in right knee extension each year in individuals with COL6-RDs. Pulmonary function demonstrated a yearly decline in sitting forced vital capacity percent predicted of 3.03% (p < 0.01) in individuals with COL6-RDs. There was no significant change in quality-of-life measures analyzed.
CONCLUSIONResults of this study describe the rate of change of motor function as measured by the MFM32, muscle strength, range of motion, and pulmonary function in individuals with COL6-RDs and LAMA2-RDs.
ABSTRACT
Introduction
Electrical impedance myography (EIM) is a noninvasive electrophysiological technique that characterizes muscle properties through bioimpedance. We compared EIM measurements to ...function, strength, and disease severity in a population with congenital muscular dystrophy (CMD).
Methods
Forty‐one patients with CMD, either collagen 6 related disorders (COL6‐RD; n = 21) or laminin α‐2‐related disorders (LAMA2‐RD; n = 20), and 21 healthy pediatric controls underwent 2 yearly EIM exams. In the CMD cohorts, EIM was compared with functional and strength measurements.
Results
Both CMD cohorts exhibited change over time and had correlation with disease severity. The 50‐kHZ phase correlated well with function and strength in the COL6‐RD cohort but not in the LAMA2‐RD cohort.
Discussion
EIM is a potentially useful measure in clinical studies with CMD because of its sensitivity to change over a 1‐year period and correlation with disease severity. For COL6‐RD, there were also functional and strength correlations. Muscle Nerve 57: 54–60, 2018
Background
Gantenerumab, a human monoclonal antibody targeting aggregated beta‐amyloid (Abeta), is a potential disease‐modifying treatment for early (prodromal‐to‐mild) Alzheimer’s disease (AD). ...SCarlet RoAD (SR) (NCT01224106) and Marguerite RoAD (MR) (NCT02051608) were two Phase III trials which assessed the efficacy and safety of subcutaneous (SC), low‐dose gantenerumab in participants with prodromal and mild AD, respectively, for up to 2 years. Following a gap period gantenerumab treatment was continued with uptitration to a dose of 1,200 mg monthly in open‐label extensions (OLE), which demonstrated substantial Abeta removal by positron emission tomography without new or unexpected safety findings. Here, we describe the study design, present baseline characteristics, and safety data from an additional open‐label, multicenter, rollover study, Open RoAD (OR) (NCT04339413), collecting long‐term safety and tolerability data for gantenerumab in participants who completed the SR OLE or MR OLE.
Method
Participants who completed either OLE study and were treated with doses up to 1,200 mg of gantenerumab for up to 5 years continue to receive the same dose of SC gantenerumab (every 4 weeks q4w) for 2 additional years in OR. The primary objective is to evaluate long‐term safety and tolerability by assessing adverse events, including amyloid‐related imaging abnormalities, and injection‐site reactions. Exploratory efficacy objectives include Mini‐Mental State Examination (MMSE) total score. The long‐term effect of gantenerumab on pharmacodynamic measures and biomarkers will also be explored.
Result
Baseline characteristics
Fifty‐nine participants from SR OLE and 56 participants from MR OLE received at least one dose of gantenerumab in OR. The median participant age at baseline was 78 years, and the majority of the participants were female (61%). Sixty‐seven percent of participants were apolipoprotein‐E‐e4 (APOE e4) carriers. The median total MMSE score at baseline was 16.
Safety data will be presented.
Conclusion
The RoAD studies are among the longest‐duration OLEs of an anti‐amyloid monoclonal antibody. Data from the OR study demonstrate that gantenerumab at doses of 1,200 mg administered SC q4w is well tolerated, with no new or unexpected safety findings in patients with early AD.
The process optimization of a key step in the synthesis of NLRP3 (nucleotide-binding domain and leucine-rich repeat-containing protein 3) agonist BMS-986299 is reported. The step is a convergent ...three-stage telescope featuring four discrete chemical transformations: a Pd-catalyzed Miyaura borylation, followed by a Suzuki–Miyaura cross-coupling, then a concurrent acid-mediated cyclization and THP (tetrahydropyran) cleavage. Through targeted process development focused on safety, sustainability, and robustness, we developed safer and more robust borylation conditions to generate an aryl boronate ester intermediate that is then taken into a nonaqueous Suzuki–Miyaura reaction via a streamlined telescoped sequence and a subsequent kinetic analysis-driven reactive crystallization to synthesize the imidazole-fused 2-aminoquinoline core of BMS-986299. Overall, the improvements discussed herein resulted in a greener, safer, and more robust process for the synthesis of this intermediate.
In kinetoplastid parasites, regulation of mitochondrial gene expression occurs posttranscriptionally via RNA stability and RNA editing. In addition to the 20S editosome that contains the enzymes ...required for RNA editing, a dynamic complex called the mitochondrial RNA binding 1 (MRB1) complex is also essential for editing. Trypanosoma brucei RGG3 (TbRGG3) was originally identified through its interaction with the guide RNA-associated proteins 1 and 2 (GAP1/2), components of the MRB1 complex. Both the arginine-glycine-rich character of TbRGG3, which suggests a function in RNA binding, and its interaction with MRB1 implicate TbRGG3 in mitochondrial gene regulation. Here, we report an in vitro and in vivo characterization of TbRGG3 function in T. brucei mitochondria. We show that in vitro TbRGG3 binds RNA with broad sequence specificity and has the capacity to modulate RNA-RNA interactions. In vivo, inducible RNA interference (RNAi) studies demonstrate that TbRGG3 is essential for proliferation of insect vector stage T. brucei. TbRGG3 ablation does not cause a defect in RNA editing but, rather, specifically affects the abundance of two preedited transcripts as well as their edited counterparts. Protein-protein interaction studies show that TbRGG3 associates with GAP1/2 apart from the remainder of the MRB1 complex, as well as with several non-MRB1 proteins that are required for mitochondrial RNA editing and/or stability. Together, these studies demonstrate that TbRGG3 is an essential mitochondrial gene regulatory factor that impacts the stabilities of specific RNAs.
The complex parasite communities of animals contribute to biodiversity, yet the conservation strategies that aim to preserve individual threatened species often overlook their parasite communities. ...Deeper understanding of parasite communities and how they are affected by management is important to the ultimate success of biodiversity conservation. Here we examine the dynamics between the coccidian parasite Eimeria and the threatened brush-tailed rock-wallaby (Petrogale penicillata, BTRW) to determine how parasite communities respond to the conservation management practices of captive breeding and translocation. Three BTRW population categories (wild, captive bred or supplemented) were analysed for Eimeria prevalence and infection intensity and a metagenomic assessment performed to examine community structure. Eimeria prevalence was 92% in 117 faecal samples. DNA amplicons from purified oocysts were sequenced with the Illumina MiSeq platform and the resulting sequences assigned to 28 Eimeria operational taxonomic units (OTUs). Pairwise identity between OTUs was 89.9% and 25 of the Eimeria OTUs formed a highly supported phylogenetic clade with marsupial specific Eimeria species, indicating strong host specificity and genetic diversity within Eimeria in BTRWs. Supplemented populations had the greatest OTU diversity with eleven unique OTUs and had a greater overlap with captive bred (9 shared OTUs) versus wild populations (6 shared OTUs). There was no significant effect of population category on infection intensity (p=0.965), OTU composition (p=0.51) or richness (p=0.490), suggesting that Eimeria community structure is maintained under the management processes applied to the BTRW. Our approach can be applied to other parasite communities in hosts under conservation management.
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•Eimeria communities were analysed in wallaby populations in a conservation program.•Eimeria was almost ubiquitous across all populations with 92% prevalence.•Conservation management had no significant effect on infection intensity of Eimeria.•Eimeria community structure was analysed with next generation sequencing.•The biodiversity of Eimeria communities was conserved across populations.
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