Sunnybrook Health Sciences Centre

About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

Adding gabapentin to a multimodal regimen does not reduce acute pain, opioid consumption or chronic pain after total hip arthroplasty.

Abstract: Background: Gabapentin (GPN) is effective in reducing post-operative pain and opioid consumption, but its effects with regional anesthesia for total hip arthroplasty (THA) are not known. We designed this study to determine whether (1) gabapentin administration reduces pain and opioid use after THA using a multimodal analgesic regimen including spinal anesthesia; (2) pre-operative administration of gabapentin is more effective than post-operative administration. Methods: After REB approval and informed consent, 126 patients were enrolled in a double-blinded, randomized-controlled study. Patients received acetaminophen 1 g per os (p.o.), celecoxib 400 mg p.o. and dexamethasone 8 mg intravenously, 1-2h pre-operatively. Patients were randomly assigned to one of three treatment groups (G1: Placebo/Placebo; G2: GPN/Placebo; G3: Placebo/GPN). Patients received gabapentin 600 mg (G2) or placebo (G1 and G3) 2 h before surgery. All patients had spinal anesthesia [15 mg (3cc) of 0.5% hypobaric bupivacaine with 10 μg of fentanyl]. In the post-anesthetic care unit, patients received gabapentin 600 mg (G3) or placebo (G1 and G2). On the ward, patients received acetaminophen 1000 mg p.o. q6h, celecoxib 200 mg p.o. q12h and a morphine PCA device. Patients were interviewed 6 months post-surgery to determine the incidence and severity of chronic post-surgical pain. Results: Mean ± SD cumulative morphine (mg) consumption (G1 = 49.4 ± 24.8, G2 = 47.2 ± 30.1 and G3 = 56.1 ± 38.2) at 48 h and pain scores at 12, 24, 36 and 48 h post-surgery were not significantly different among the groups [G1 (n = 38), G2 (n = 38) and G3 (n = 38)]. Side effect profiles were similar across groups. Six months after surgery, the number of patients who reported chronic post-surgical pain (G1 = 10, G2 = 12 and G3 = 9) and the severity of the pain (G1 = 4.2 ± 2.9, G2 = 4.1 ± 2.2 and G3 = 4.9 ± 2.2) did not differ significantly among the groups (P > 0.05). Conclusions: A single 600 mg dose of gabapentin given pre-operatively or post-operatively does not reduce morphine consumption or pain scores in hospital or at 6 months after hip arthroplasty within the context of spinal anesthesia and a robust multimodal analgesia regimen.

Inter-observer reliability of ten tests used for predicting difficult tracheal intubation

Abstract: To determine inter-observer reliability of ten preoperative airway assessment tests used for predicting difficult tracheal intubation. We prospectively assessed 59 patients undergoing elective surgery requiring tracheal intubation at a large metropolitan teaching hospital. Two experienced observers independently conducted the airway assessment tests on the same group of patients. Inter-observer reliability was examined using Kappa (K) and intraclass correlation coefficient (ICC). Two tests — mouth opening (ICC = 0.93) and chin protrusion (ICC = 0.89) — had excellent inter-observer reliability. Seven tests — thyromental distance (ICC =0.74), subluxation (K = 0.66), atlanto-occipital extension distance (ICC = 0.67) and angle (K = 0.66), profile classification (K = 0.58), ramus length (ICC = 0.53), oropharyngeal best view (K = 0.49) — were moderately reliable. One test — Mallampati technique of assessing oropharyngeal view (K = 0.31) — had poor reliability. Many of the preoperative airway tests have only moderate inter-observer reliability. This may provide some insight into why previous research has failed to show that the tests accurately predict difficult tracheal intubation.

Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia

Abstract: OBJECTIVE: To estimate the prevalence of amyloid-positivity, defined by PET/CSF biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. METHODS: We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n=443], non-fluent [nfvPPA, n=333], semantic [svPPA, n=401] and mixed/unclassifiable [PPA-M/U, n=74] variants of PPA) from 36 centers, with a measure of amyloid-β pathology (CSF [n=600]), PET [n=366] and/or autopsy [n=378]) available. The estimated prevalence of amyloid-positivity according to PPA variant, age and apolipoprotein E (APOE) e4 status was determined using generalized estimating equation models. RESULTS: Amyloid-β positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%) (p<0.001). Prevalence of amyloid-β positivity increased with age in nfvPPA (from 10% at age 50 to 27% at age 80, p<0.01) and svPPA (from 6% at age 50 to 32% at age 80, p<0.001), but not in lvPPA (p=0.94). Across PPA variants, APOE e4 carriers were more often amyloid-β positive (58.0%) than non-carriers (35.0%, p<0.001). Autopsy data revealed Alzheimer's disease (AD) pathology as the most common pathologic diagnosis in lvPPA (76%), frontotemporal lobar degeneration - TDP-43 in svPPA (80%) and frontotemporal lobar degeneration-TDP-43/tau in nfvPPA (64%). INTERPRETATION: This study shows that the current PPA classification system helps to predict underlying pathology across different cohorts and clinical settings, and suggests that age and APOE genotype should be taken into account when interpreting Aβ biomarkers in PPA patients. This article is protected by copyright. All rights reserved.

Aberrant O-GlcNAcylation characterizes chronic lymphocytic leukemia

Abstract: O-linked N-Acetylglucosamine (O-GlcNAc) post-translational modifications originate from the activity of the hexosamine pathway, and are known to affect intracellular signaling processes. As aberrant responses to microenvironmental signals are a feature of chronic lymphocytic leukemia (CLL), O-GlcNAcylated protein levels were measured in primary CLL cells. In contrast to normal circulating and tonsillar B cells, CLL cells expressed high levels of O-GlcNAcylated proteins, including p53, c-myc and Akt. O-GlcNAcylation in CLL cells increased following activation with cytokines and through toll-like receptors (TLRs), or after loading with hexosamine pathway substrates. However, high baseline O-GlcNAc levels were associated with impaired signaling responses to TLR agonists, chemotherapeutic agents, B cell receptor crosslinking and mitogens. Indolent and aggressive clinical behavior of CLL cells were found to correlate with higher and lower O-GlcNAc levels, respectively. These findings suggest that intracellular O-GlcNAcylation is associated with the pathogenesis of CLL, which could potentially have therapeutic implications.