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5. An in vitro evaluation of intravenous lipid emulsion on three common canine toxicants

Author

Emery Jones, Stuart A. Walton, Jennifer Davis, and McAlister Council-Troche

Subjects
intravenous lipid emulsion, baclofen, bromethalin, ibuprofen, toxicosis, Veterinary medicine, SF600-1100
Abstract

ObjectiveTo determine whether intravenous lipid emulsion (ILE) therapy significantly reduces the concentration of baclofen, ibuprofen, and/or bromethalin in canine whole blood over time.AnimalsSeven 500 mL bags of canine DEA 1.1 negative blood were divided into aliquots of 125 mL and randomly assigned to one of three treatment groups (baclofen, ibuprofen, bromethalin) or four control groups (a positive control for each treatment group and a negative control group).ProceduresInjectable ibuprofen (200 mg/kg), baclofen (8 mg/kg), or bromethalin (3 mg/kg) was apportioned into 125 mL aliquots of canine whole blood and incubated for 30 min at 38.5°C. ILE (12.4 mL, Intralipid®) was added to each sample and the solution vortexed [215 rpm for 15 min at 37°C (98.6°F)]. Samples were obtained at designated time points (0, 15, 30, 60, 180, 360 min), centrifuged, and separated into serum and RBC fractions. Serum samples were ultracentrifuged (22,000 g for 10 min at 37°C) to separate lipid rich and poor fractions. Samples were stored at −80°C prior to analysis.ResultsA significant decrease in total drug concentration was established for bromethalin and its metabolite desmethylbromethalin compared to positive controls. ILE significantly reduced desmethylbromethalin at the 30-and 360-min time points. The remainder of the desmethylbromethalin time points did not reach significance. Bromethalin concentration was significantly reduced at all time points compared to positive controls. Neither baclofen nor ibuprofen had significant changes in concentration.ConclusionILE therapy was effective at reducing the total drug concentration of bromethalin and its metabolite desmethylbromethalin supporting the lipid sink theory. As a single compartment in vitro study, this study does not evaluate other proposed mechanisms of action of ILE therapy. ILE therapy may have other means of significantly decreasing lipophilic drug concentration in cases of toxicosis.

Published
2024
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24. LETTERS.

Author

POWELL, IRENE, KELLEY, HELEN M., STONE, ANDREA G., TATE, JOHN P., HEFT, ALICE, DREXLER, F. I., PLUMER, DAVENPORT, PLUMER, MARCIA, MCALISTER, C. H. SCOTT, CLARK, T. F., BOHMER, RALPH, WARD, I. W., DALEY, JOHN P., CHADWICK, RONALD S., JACOBS, S., MONTGOMERY, PAUL, PETTY, RICHARD P., COFFEY, EDWARD J., YASINITSKY, S. G., and BRONSKY, IRVING

Subjects
MODERN art exhibitions, PRESIDENTIAL candidates
Published
1956

27. Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study

Author

Khan Mohammad Imran, Benjamin Tintera, Holly A. Morrison, Juselyn D. Tupik, Margaret A. Nagai-Singer, Hannah Ivester, McAlister Council-Troche, Michael Edwards, Sheryl Coutermarsh-Ott, Christopher Byron, Sherrie Clark-Deener, Kyungjun Uh, Kiho Lee, Paul Boulos, Cliff Rowe, Christian Coviello, and Irving C. Allen

Subjects
pancreatic cancer, paclitaxel, gemcitabine, cetuximab, drug delivery, SonoTran Particles, Pharmacy and materia medica, RS1-441
Abstract

Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.

Published
2023
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28. Developing spatial infrastructures for the Q.U.T. Samford Ecological Research Facility

Author

Searle, L, McAlister, C, Webb, Robert, Searle, L, McAlister, C, and Webb, Robert

Abstract

Staff and students of the Surveying and Spatial Sciences discipline at QUT have worked collaboratively with the Institute of Sustainable Resources in the creation and development of spatial information layers and infrastructure to support multi-disciplinary research efforts at the Samford Ecological Research Facility (SERF). The SERF property is unique in that it provides staff and students with a semi-rural controlled research base for multiple users. This paper aims to describe the development of a number of spatial information layers and network of survey monuments that assist and support research infrastructure at SERF. A brief historical background about the facility is presented along with descriptions of the surveying and mapping activities undertaken. These broad ranging activities include introducing monument infrastructure and a geodetic control network; surveying activities for aerial photography ground-control targets including precise levelling with barcode instruments; development of an ortho-rectified image spatial information layer; Real-Time-Kinematic Global Positioning Systems (RTK-GPS) surveying for constructing 100metre confluence points/monuments to support science-based disciplines to undertake environmental research transects and long-term ecological sampling; and real-world learning initiative to assist with water engineering projects and student experiential learning. The spatial information layers and physical infrastructure have been adopted by two specific yet diverse user groups with an interest in the long-term research focus of SERF.

Published
2010

30. Canadian Surgery Forum1 Is laparoscopic sleeve gastrectomy a reasonable stand-alone procedure for super morbidly obese patients?2 Postoperative monitoring requirements of patients with obstructive sleep apnea undergoing bariatric surgery3 Role of relaparoscopy in the diagnosis and treatment of bariatric complications in the early postoperative period4 Changes of active and total ghrelin, GLP-1 and PYY following restrictive bariatric surgery and their impact on satiety: comparison of sleeve gastrectomy and adjustable gastric banding5 Prioritization and willingness to pay for bariatric surgery: the patient perspective6 Ventral hernia at the time of laparoscopic gastric bypass surgery: Should it be repaired?7 Linear stapled gastrojejunostomy with transverse handsewn enterotomy closure significantly reduces strictures for laparoscopic Roux-en-Y bypass8 Laparoscopic biliopancreatic diversion with duodenal switch as second stage for super super morbidly obese patients. Do all patients benefit?9 Sleeve gastrectomy in the super super morbidly obese (BMI > 60 kg/m2): a Canadian experience10 Laparoscopic gastric bypass for the treatment of refractory idiopathic gastroparesis: a report of 2 cases11 Duodeno-ileal switch as a primary bariatric and metabolic surgical option for the severely obese patient with comorbidities: review of a single-institution case series of duodeno-ileal intestinal bypass12 Management of large paraesophageal hernias in morbidly obese patients with laparoscopic sleeve gastrectomy: a case series13 Early results of the Ontario bariatric surgical program: using the bariatric registry14 Improving access to bariatric surgical care: Is universal health care the answer?15 Early and liberal postoperative exploration can reduce morbidity and mortality in patients undergoing bariatric surgery16 Withdrawn17 Identification and assessment of technical errors in laparoscopic Roux-en-Y gastric bypass18 A valid and reliable tool for assessment of surgical skill in laparoscopic Roux-en-Y gastric bypass19 Psychiatric predictors of presurgery drop-out following suitability assessment for bariatric surgery20 Predictors of outcomes following Roux-en-Y gastric bypass surgery at The Ottawa Hospital21 Prophylactic management of cholelithiasis in bariatric patients: Is routine cholecystectomy warranted?22 Early outcomes of Roux-en-Y gastric bypass in a publicly funded obesity program23 Similar incidence of gastrojejunal anastomotic stricture formation with hand-sewn and 21 mm circular stapler techniques during Roux-en-Y gastric bypass24 (CAGS Basic Science Award) Exogenous glucagon-like peptide-1 improves clinical, morphological and histological outcomes of intestinal adaptation in a distal-intestinal resection piglet model of short bowel syndrome25 (CAGS Clinical Research Award) Development and validation of a comprehensive curriculum to teach an advanced minimally invasive procedure: a randomized controlled trial26 Negative-pressure wound therapy (iVAC) on closed, high-risk incisions following abdominal wall reconstruction27 The impact of seed granting on research in the University of British Columbia Department of Surgery28 Quality of surgical care is inadequate for elderly patients29 Recurrence of inguinal hernia in general and hernia specialty hospitals in Ontario, Canada30 Oncostatin M receptor deficiency results in increased mortality in an intestinal ischemia reperfusion model in mice31 Laparoscopic repair of large paraesophageal hernias with anterior gastropexy: a multicentre trial32 Response to preoperative medical therapy predicts success of laparoscopic splenectomy for immune thrombocytopenic purpura33 Perioperative sepsis, but not hemorrhagic shock, promotes the development of cancer metastases in a murine model34 Measuring the impact of implementing an acute care surgery service on the management of acute biliary disease35 Patient flow and efficiency in an acute care surgery service36 The relationship between treatment factors and postoperative complications after radical surgery for rectal cancer37 Risk of ventral hernia after laparoscopic colon surgery38 Urinary metabolomics as a tool for early detection of Barrett’s and esophageal cancer39 Construct validity of individual and summary performance metrics associated with a computer-based laparo-scopic simulator40 Impact of a city-wide health system reorganization on emergency department visits in hospitals in surrounding communities41 Transcatheter aortic valve implantation for the nonoperative management of aortic stenosis: a cost-effectiveness analysis42 Breast cancer: racial differences in age of onset. A potential confounder in Canadian screening recommendations43 Risk taking in surgery: in and out of the comfort zone44 A tumour board in the office: Track those cancer patients!45 Increased patient BMI is not associated with advanced colon cancer stage or grade on presentation: a retrospective chart review46 Consensus statements regarding the multidisciplinary care of limb amputation patients in disasters or humanitarian emergencies. Report of the 2011 Humanitarian Action Summit Surgical Working Group on amputations following disasters or conflict47 Learning the CanMEDS role of professional: a pilot project of supervised discussion groups addressing the hidden curriculum48 Assessing the changing scope of training in Canadian general surgery programs: expected versus actual experience49 Predicting need for surgical management for massive gastrointestinal hemorrhage50 International health care experience: using CanMEDS to evaluate learning outcomes following a surgical mission in Mampong, Ghana51 The open abdomen: risk factors for mortality and rates of closure52 How surgeons think: an exploration of mental practice in surgical preparation53 The surgery wiki: a novel method for delivery of under-graduate surgical education54 Understanding surgical residents’ postoperative practices before implementing an enhanced recovery after surgery (ERAS) guideline at the University of Toronto55 From laparoscopic transabdominal to posterior retroperitoneal adrenalectomy: a paradigm shift in operative approach56 A retrospective audit of outcomes in patients over the age of 80 undergoing acute care abdominal surgery57 Canadian general surgery residents’ perspectives on work-hour regulations58 Timing of surgical intervention and its outcomes in acute appendicitis59 Preparing surgical trainees to deal with adverse events. An outline of learning issues60 Acute care surgical service: surgeon agreement at the time of handover61 Predicting discharge of elderly patients to prehospitalization residence following emergency general surgery62 Morbidity and mortality after emergency abdominal surgery in octo- and nonagenarians63 The impact of acute abdominal illness and urgent admission to hospital on the living situation of elderly patients64 A comparison of laparoscopic versus open subtotal gastrectomy for antral gastric adenocarcinoma: a North American perspective65 Minimally invasive excision of ectopic mediastinal parathyroid adenomas66 Perioperative outcomes of laparoscopic hernia repair in a tertiary care centre: a single institution’s experience67 Evaluation of a student-run, practical and didactic curriculum for preclerkship medical students68 Joseph Lister: Father of Modern Surgery69 Comparisons of melanoma sentinel lymph node biopsy prediction nomograms in a cohort of Canadian patients70 Local experience with myocutaneous flaps after extensive pelvic surgery71 The treatment of noncirrhotic splanchnic vein thrombosis: Is anticoagulation enough?72 Implementation of an acute care surgery service does not affect wait-times for elective cancer surgeries: an institutional experience73 Use of human collagen mesh for closure of a large abdominal wall defect, after colon cancer surgery, a case report74 The role of miR-200b in pulmonary hypoplasia associated with congenital diaphragmatic hernia75 Systematic review and meta-analysis of electrocautery versus scalpel for incising epidermis and dermis76 Accuracy of sentinel lymph node biopsy for early breast cancer in the community setting in St. John’s, New-foundland: results of a retrospective review77 Acute surgical outcomes in the 80 plus population78 The liberal use of platelets transfusions in the acute phase of trauma resuscitation: a systematic review79 Implementation of an acute care surgical on call program in a Canadian community hospital80 Short-term outcomes following paraesophageal hernia repair in the elderly patient81 First experience with single incision surgery: feasibility in the pediatric population and cost evaluation82 The impact of the establishment of an acute care surgery unit on the outcomes of appendectomies and cholecystectomies83 Description and preliminary evaluation of a low-cost simulator for training and evaluation of flexible endoscopic skills84 Tumour lysis syndrome in metastatic colon cancer: a case report85 Acute care surgery service model implementation study at a single institution86 Colonic disasters approached by emergent subtotal and total colectomy: lessons learned from 120 consecutive cases87 Acellular collagen matrix stent to protect bowel anastomoses88 Lessons we learned from preoperative MRI-guided wire localization of breast lesions: the University Health Network (UHN) experience89 Interim cost comparison for the use of platinum micro-coils in the operative localization of small peripheral lung nodules90 Routine barium esophagram has minimal impact on the postoperative management of patients undergoing esophagectomy for esophageal cancer91 Iron deficiency anemia is a common presenting issue with giant paraesophageal hernia and resolves following repair92 A randomized comparison of different ventilation strategies during thoracotomy and lung resection93 The Canadian Lung Volume Reduction Surgery study: an 8-year follow-up94 A comparison of minimally invasive versus open Ivor-Lewis esophagectomy95 A new paradigm in the follow-up after curative resection for lung cancer: minimal-dose CT scan allows for early detection of asymptomatic cancer activity96 Predictors of lymph node metastasis in early esophageal adenocarcinoma: Is endoscopic resection worth the risk?97 How well can thoracic surgery residents operate? Comparing resident and program director opinions98 The impact of extremes of age on short- and long-term outcomes following surgical resection of esophageal malignancy99 Epidermal growth factor receptor targeted gold nanoparticles for the enhanced radiation treatment of non–small cell lung cancer100 Laparoscopic Heller myotomy results in excellent outcomes in all subtypes of achalasia as defined by the Chicago classification101 Neoadjuvant chemoradiation versus surgery in managing esophageal cancer102 Quality of life postesophagectomy for cancer!103 The implementation, evolution and translocation of standardized clinical pathways can improve perioperative outcomes following surgical treatment of esophageal cancer104 A tissue-mimicking phantom for applications in thoracic surgical simulation105 Sublobar resection compared with lobectomy for early stage non–small cell lung cancer: a single institution study106 Not all reviews are equal: the quality of systematic reviews and meta-analyses in thoracic surgery107 Do postoperative complications affect health-related quality of life after video-assisted thoracoscopic lobectomy for patients with lung cancer? A cohort study108 Thoracoscopic plication for palliation of dyspnea secondary to unilateral diaphragmatic paralysis: A worthwhile venture?109 Thoracic surgery experience in Canadian general surgery residency programs110 Perioperative morbidity and pathologic response rates following neoadjuvant chemotherapy and chemoradiation for locally advanced esophageal carcinoma111 An enhanced recovery pathway reduces length of stay after esophagectomy112 Predictors of dysplastic and neoplastic progression of Barrett’s esophagus113 Recurrent esophageal cancer complicated by tracheoesophageal fistula: management by means of palliative airway stenting114 Pancreaticopleural fistula-induced empyema thoracis: principles and results of surgical management115 Prognostic factors of early postoperative mortality following right extended hepatectomy116 Optimizing steatotic livers for transplantation using a cell-penetrating peptide CPP-fused heme oxygenase117 Video outlining the technical steps for a robot-assisted laparoscopic pancreaticoduodenectomy118 Establishment of a collaborative group to conduct innovative clinical trials in Canada119 Hepatic resection for metastatic malignant melanoma: a systematic review and meta-analysis120 Acellular normothermic ex vivo liver perfusion for donor liver preservation121 Pancreatic cancer and predictors of survival: comparing the CA 19–9/bilirubin ratio with the McGill Brisbane Scoring System122 Staged liver resections for bilobar hepatic colorectal metastases: a single centre experience123 Economic model of observation versus immediate resection of hepatic adenomas124 Resection of colorectal liver metastasis in the elderly125 Acceptable long-term survival in patients undergoing liver resection for metastases from noncolorectal, non-neuroendocrine, nonsarcoma malignancies126 Patient and clinicopathological features and prognosis of CK19+ hepatocellular carcinomas: a case–control study127 The management of blunt hepatic trauma in the age of angioembolization: a single centre experience128 Liver resections for noncolorectal and non-neuroendocrine metastases: an evaluation of oncologic outcomes129 Developing an evidence-based clinical pathway for patients undergoing pancreaticoduodenectomy130 Hepatitis C infection and hepatocellular carcinoma in liver transplant: a 20 year experience131 The effect of medication on the risk of post-ERCP pancreatitis132 Temporal trends in the use of diagnostic imaging for patients with hepato-pancreato-biliary (HPB) conditions: How much ionizing radiation are we really using?196 A phase II study of aggressive metastasectomy for intra-and extrahepatic metastases from colorectal cancer133 Why do women choose mastectomy for breast cancer treatment? A conceptual framework for understanding surgical decision-making in early-stage breast cancer134 Synoptic operative reporting: documentation of quality of care data for rectal cancer surgery135 Learning curve analysis for cytoreductive surgery: a useful application of the cumulative sum (CUSUM) method136 Pancreatic cancer is strongly associated with a unique urinary metabolomic signature137 Concurrent neoadjuvant chemo/radiation in locally advanced breast cancer138 Impact of positron emission tomography on clinical staging of newly diagnosed rectal cancer: a specialized single centre retrospective study139 An evaluation of intraoperative Faxitron microradiography versus conventional specimen radiography for the excision of nonpalpable breast lesions140 Comparison of breast cancer treatment wait-times in the Southern Interior of British Columbia in 2006 and 2010141 Factors affecting lymph nodes harvest in colorectal carcinoma142 Laparoscopic adrenalectomy for metastases143 You have a message! Social networking as a motivator for fundamentals of laparoscopic surgery (FLS) training144 The evaluation and validation of a rapid diagnostic and support clinic for women assessment for breast cancer145 Oncoplastic breast surgery: oncologic benefits and limitations146 A qualitative study on rectal cancer patients’ preferences for location of surgical care147 The effect of surgery on local recurrence in young women with breast cancer148 Elevated IL-6 and IL-8 levels in tumour microenvironment is not associated with increased serum levels in humans with Pseudomyxoma peritonei and peritoneal mesothelioma149 Conversion from laparoscopic to open approach during gastrectomy: a population-based analysis150 A scoping review of surgical process improvement tools (SPITs) in cancer surgery151 Splenectomy during gastric cancer surgery: a population-based study152 Defining the polo-like kinase 4 (Plk4) interactome in cancer cell protrusions153 Neoadjuvant imatinib mesylate for locally advanced gastrointestinal stromal tumours154 Implementing results from ACOSOG Z0011: Practice-changing or practice-affirming?155 Should lymph node retrieval be a surgical quality indicator in colon cancer?156 Long-term outcomes following resection of retroperitoneal recurrence of colorectal cancer157 Clinical research in surgical oncology: an analysis of clinicaltrials.gov158 Radiation therapy after breast conserving surgery: When are we missing the mark?159 The accuracy of endorectal ultrasound in staging rectal lesions in patients undergoing transanal endoscopic microsurgery160 Quality improvement in gastrointestinal cancer surgery: expert panel recommendations for priority research areas161 Factors influencing the quality of local management of ductal carcinoma in situ: a cohort study162 Papillary thyroid microcarcinoma: Does size matter?163 Hyperthermic isolated limb perfusion for extremity soft tissue sarcomas: systematic review of clinical efficacy and quality assessment of reported trials164 Adherence to antiestrogen therapy in seniors with breast cancer: How well are we doing?165 Parathyroid carcinoma: Challenging the surgical dogma?166 A qualitative assessment of the journey to delayed breast reconstruction195 The role of yoga therapy in breast cancer patients167 Outcomes reported in comparative studies of surgical interventions168 Enhanced recovery pathways decrease length of stay following colorectal surgery, but how quickly do patients actually recover?169 The impact of complications on bed utilization after elective colorectal resection170 Impact of trimodal prehabilitation program on functional recovery after colorectal cancer surgery: a pilot study171 Complex fistula-in-ano: Should the plug be abandoned in favour of the LIFT or BioLIFT?172 Prognostic utility of cyclooxygenase-2 expression by colon and rectal cancer173 Laparoscopic right hemicolectomy with complete mesocolic excision provides acceptable perioperative outcomes but is complex and time-consuming: analysis of learning curves for a novice minimally invasive surgeon174 Intraoperative quality assessment following double stapled circular colorectal anastomosis175 Improving patient outcomes through quality assessment of rectal cancer care176 Are physicians willing to accept a decrease in treatment effectiveness for improved functional outcomes for low rectal cancer?177 Turnbull-Cutait delayed coloanal anastomosis for the treatment of distal rectal cancer: a prospective cohort study178 Preoperative high-dose rate brachytherapy in preparation for sphincter preservation surgery for patients with advanced cancer of the lower rectum179 Impact of an enhanced recovery program on short-term outcomes after scheduled laparoscopic colon resection180 The clinical results of the Turnbull-Cutait delayed coloanal anastomosis: a systematic review181 Is a vertical rectus abdominus flap (VRAM) necessary? An analysis of perineal wound complications182 Fistula plug versus endorectal anal advancement flap for the treatment of high transsphincteric cryptoglandular anal fistulas: a systematic review and meta-analysis183 Maternal and neonatal outcomes following colorectal cancer surgery184 Transanal drainage to treat anastomotic leaks after low anterior resection for rectal cancer: a valuable option185 Trends in colon cancer in Ontario: 2002–2009186 Validation of electronically derived short-term outcomes in colorectal surgery187 A population-based assessment of transanal and endoscopic resection for adenocarcinoma of the rectum188 Laparoscopic colorectal surgery in the emergency setting: trends in the province of Ontario from 2002 to 2009189 Prevention of perineal hernia after laparoscopic and robotic abdominoperineal resection: review with case series of internal hernia through pelvic mesh which was placed in attempt to prevent perineal hernia190 Effect of rectal cancer treatments on quality of life191 The use of antibacterial sutures as an adjunctive preventative strategy for surgical site infection in Canada: an economic analysis192 Impact of socioeconomic status on colorectal cancer screening and stage at presentation: preliminary results of a population-based study from an urban Canadian centre193 Initial perioperative results of the first transanal endoscopic microsurgery (TEM) program in the province of Quebec194 Use of negative pressure wound therapy decreases perineal wound infections following abdominal perineal resection

Author

Fayez, R., primary, AlMuntashery, A., primary, Bodie, G., primary, Almamar, A., primary, Gill, R.S., primary, Raîche, I., primary, Mueller, C.L., primary, Moustarah, F., primary, Khokhotva, M., primary, Anvari, M., primary, Kwong, J., primary, Elkassem, S., primary, Bonrath, E., primary, Zevin, B., primary, Sockalingam, S., primary, Smith, C., primary, Whitlock, K.A., primary, Suri, M., primary, Palter, V.N., primary, Wakeam, E., primary, Khan, R.S.A., primary, Martelli, V., primary, Malik, A., primary, Young, P.Y., primary, Daigle, C., primary, McCreery, G., primary, Seth, R., primary, Paskar, D., primary, Sudarshan, M., primary, Richardson, D., primary, Haggar, F., primary, Davis, V.W., primary, Rivard, J., primary, Agzarian, J., primary, Racz, J., primary, Winocour, J., primary, Zilbert, N.R., primary, Decker, C., primary, Neumann, K., primary, Gosney, J.E., primary, Wissanji, H., primary, Chadi, S.A., primary, Alhabboubi, M., primary, Partridge, E., primary, Olszewski, M., primary, Chan, R., primary, Nadler, A., primary, Hameed, U., primary, Brotherhood, H., primary, Menezes, A.S., primary, MacDonald, B., primary, Rakovich, G., primary, Hilsden, R., primary, Merani, S., primary, Davis, P., primary, Davis, P.J.B., primary, Cools-Lartigue, J., primary, Ojah, J., primary, Julien, F., primary, Carter, D., primary, Pitt, D., primary, Banks, B.A., primary, Rudovics, A., primary, Ravichandran, P., primary, Anantha, R., primary, Aad, I., primary, Kholdebarin, R., primary, Aird, L.N.F., primary, Wong, S.L., primary, Payne, J.R.M., primary, Hallet, J., primary, Farries, L., primary, Raiche, I., primary, Botkin, C., primary, Morency, D., primary, Berger-Richardson, D., primary, Isa, A.D., primary, Dupuis, I, primary, Schweigert, M., primary, Koubi, S., primary, Ernjakovic, M., primary, Grant, K., primary, Carrott, P., primary, Stafford, T., primary, Malthaner, R., primary, Hanna, W.C., primary, Lee, L., primary, Markar, S., primary, Razzak, R., primary, Bharadwaj, S.C., primary, Ashrafi, A.S., primary, Ouellette, D., primary, Bottoni, D.A., primary, Knickle, C., primary, Coughlin, S., primary, Gazala, S., primary, Donahoe, L., primary, Walker, K., primary, Li, C., primary, Alnasser, S., primary, Zhuruk, A., primary, Hanouf, A., primary, Vanounou, T., primary, Karanicolas, P., primary, Aubin, J.-M., primary, Yeung, J.C., primary, Dumitra, S., primary, Simoneau, E., primary, Vanounou, T.T., primary, Howe, B., primary, Hawel, J., primary, Jang, J.-H., primary, Bertens, K., primary, Rekman, J.F., primary, Wei, A.C., primary, Ouellet, J.-F., primary, Covelli, A., primary, Maniar, R., primary, Sun, S., primary, Brackstone, M., primary, Boissonneault, R., primary, Kim, S.H.H., primary, Baliski, C., primary, Arnaout, A., primary, Wedman, D., primary, Nostedt, M., primary, Hebbard, P., primary, Shetty, S.J., primary, Dixon, M., primary, Kazazian, K., primary, Lemke, M., primary, Wells, B., primary, Musselman, R.P., primary, Zih, F. Si Wai, primary, Nassif, M., primary, Leon-Carlyle, M., primary, Krotneva, S., primary, Bradley, N.L., primary, Trabulsi, N., primary, Chin-Lenn, L., primary, Cheng, H., primary, Petrucci, A.M., primary, Sandhu, L., primary, Neville, A., primary, Yang, I., primary, Prabhu, K. Lobo, primary, Melich, G., primary, Knowles, S., primary, Borowiec, A.M., primary, Kolozsvari, N.O., primary, Tuttle, P., primary, VanHouwelingen, L., primary, Boulanger-Gobeil, C., primary, Chan, B.P., primary, Phang, P.T., primary, Goldstein, L.J., primary, Wen, C., primary, Lebrun, A., primary, Roy, M., additional, Villeneuve, S., additional, AlMuntashery, A., additional, Demyttenaere, S., additional, Christou, N., additional, Court, O., additional, Fayez, R., additional, Bonrath, E., additional, Hagen, J., additional, Okrainec, A., additional, Sullivan, P., additional, Grantcharov, T., additional, Sharma, A., additional, Karmali, S., additional, Birch, D.W., additional, Majumdar, S.R., additional, Wang, X., additional, Tuepah, R., additional, Klarenbach, S.W., additional, Sharma, A.M., additional, Padwal, R.J., additional, Smith, C., additional, Haggar, F., additional, Moloo, H., additional, Poulin, E.C., additional, Martel, G., additional, Yelle, J.-D., additional, Mamazza, J., additional, Jackson, T.D., additional, Penner, T., additional, Pitzul, K., additional, Urbach, D.R., additional, Biertho, L., additional, Hould, F.-S., additional, Lebel, S., additional, Lescelleur, O., additional, Marceau, S., additional, Marceau, P., additional, Biron, S., additional, Yusuf, S., additional, Pitzul, K.B., additional, Jackson, T., additional, Lindsay, D., additional, Smith, L., additional, Zevin, B., additional, Dedy, N., additional, Grantcharov, T.P., additional, Bonrath, E.M., additional, Aggarwal, R., additional, Cassin, S., additional, Crawford, S., additional, Khan, A., additional, Hawa, R., additional, Brar, B., additional, Raîche, I., additional, Dent, R., additional, Gill, R.S., additional, Ali, T., additional, Shi, X., additional, Whitlock, K.A., additional, Sarkhosh, K., additional, Turner, J.M., additional, Nation, P.N., additional, Wizzard, P., additional, Brubaker, P.L., additional, Gisalet, D.L., additional, Wales, P.W., additional, Tien, H., additional, Spencer, F., additional, Brenneman, F., additional, Kowal, J., additional, Wiseman, S.M., additional, Fraser, S.A., additional, Vedel, I., additional, Deban, M., additional, Holcroft, C., additional, Monette, M., additional, Monette, J., additional, Bergman, S., additional, Bell, C., additional, Stukel, T., additional, Mueller, T.F., additional, Lucykx, V.A., additional, Lukowski, C.M., additional, Compston, C.A., additional, Churchill, T.A., additional, Khadaroo, R.G., additional, Vogt, K., additional, Dubois, L., additional, Gray, D., additional, Ananth, A., additional, Tai, L.-H., additional, Lam, T., additional, Falls, T., additional, Souza, C., additional, Bell, J., additional, Auer, R., additional, Parry, N., additional, Leslie, K., additional, Alhabboubi, M., additional, St-Louis, E., additional, Deckelbaum, D., additional, Razek, T., additional, Feldman, L.S., additional, Khwaja, K., additional, Porter, G., additional, Johnson, P., additional, Boushey, R., additional, Raiche, I., additional, Schiller, D.E., additional, Eurich, D., additional, Sawyer, M.B., additional, Vergis, A., additional, Unger, B., additional, Hardy, K., additional, Andrew, C., additional, Gillman, L., additional, Park, J., additional, Prodger, J., additional, Kelly, W., additional, Kelly, S., additional, Prodger, D., additional, Ewara, E., additional, Martin, J., additional, Sarma, S., additional, Chu, M., additional, Schlachta, C., additional, Zaric, G., additional, Al-Ali, K., additional, Briggs, K., additional, George, R., additional, Murnaghan, M.L., additional, Leung, A., additional, Regehr, G., additional, Moulton, C.-A., additional, Mahmud, S., additional, Metcalfe, J., additional, McKay, A., additional, Hochman, D., additional, Burkle, F.M., additional, Redmond, A.D., additional, McQueen, K., additional, Desrosiers, E., additional, Gilbert, A., additional, Ott, M.C., additional, Sudarshan, M., additional, Jessula, S., additional, Alburakan, A., additional, Iqbal, S., additional, Aikins, C., additional, Roberts, N., additional, Cil, T., additional, Marshall, J., additional, Pederson, K., additional, Erichsen, S., additional, White, J., additional, Aarts, M.-A., additional, Victor, J.C., additional, Pearsall, E., additional, McLeod, R.S., additional, Penner, T.P., additional, Karimuddin, A., additional, Hall, C., additional, Bawan, S., additional, Malik, S., additional, Hayashi, A., additional, McAlister, C., additional, Zhang, N., additional, DesRosiers, Emilie, additional, Mills, A., additional, Crozier, M., additional, Lee, L., additional, Maxwell, J., additional, Partridge, E., additional, Chad, S., additional, Steigerwald, S., additional, Mapiour, D., additional, Roberts, D., additional, MacPherson, C., additional, Donahoe, L., additional, Mercer, D., additional, Hopman, W., additional, Latulippe, J.-F., additional, Knowles, S., additional, Moffat, B., additional, Switzer, N., additional, Tul, Y., additional, Widder, S., additional, Molinari, 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A.F., additional, Hardy, P., additional, Muirhead, R.M., additional, Masters, J., additional, Poulin, H. Moloo. E.C., additional, Milbrandt, C., additional, Sideris, L., additional, Grenier-Vallée, P., additional, Dubé, P., additional, Kurashima, Y., additional, Kaneva, P., additional, Fried, G.M., additional, Vassiliou, M.C., additional, Kwan, A.H.-L., additional, Solymosi, N., additional, Rauh, N., additional, Dubecz, A., additional, Renz, M., additional, Ofner, D., additional, Stein, H.J., additional, Borgaonkar, M., additional, Crystal, P., additional, Easson, A., additional, Escallon, J., additional, Reedijk, M., additional, Leong, W.L., additional, McCready, D.R., additional, Clifton, J., additional, Mayo, J., additional, Noreau-Nguyen, M., additional, Mulder, D.S., additional, Ferri, L.E., additional, Markar, S., additional, Hong, J., additional, Low, D.E., additional, Maslow, A., additional, Davignon, K., additional, Ng, T., additional, Tan, L., additional, Aruranian, J., additional, Kosa, S., additional, Murphy, G., additional, Allison, F., additional, Moshonov, H., additional, Darling, G.E., additional, Waddell, T.K., additional, De Perrot, M., additional, Cypel, M., additional, Yasufuku, K., additional, Keshavjee, S., additional, Paul, N.S., additional, Pierre, A.F., additional, Darling, G., additional, Pedneault, C., additional, Low, D., additional, Roa, W., additional, Löbenberg, R., additional, McEwan, S., additional, Bédard, E.L., additional, Louie, B.E., additional, Farivar, A.S., additional, McHugh, S.P., additional, Aye, R.W., additional, Tan-Tam, C., additional, De Vera, M., additional, Bond, R.J., additional, Ong, S.R., additional, Johal, B., additional, Schellenberg, D., additional, Po, M., additional, Nissar, S., additional, Lund, C., additional, Ahmadi, S.Y., additional, Wakil, N., additional, Rakovich, G., additional, Beauchamps, G., additional, Preston, S., additional, Baker, C., additional, Campbell, G., additional, Malthaner, R.A., additional, Bethune, D., additional, Henteleff, H., additional, Johnston, M., additional, Buduhan, G., additional, Coughlin, H. Emmerton, additional, Roth, L., additional, Bhandari, M., additional, Malthaner, R., additional, Johnson, J., additional, Kutsogiannis, J., additional, Bédard, E., additional, Rammohan, K., additional, Stewart, K., additional, Gruchy, J., additional, Xu, Z., additional, Ncuti, A., additional, Neville, A., additional, Watson, D., additional, Vassiliou, M., additional, Carli, F., additional, Av, R., additional, Mayrand, S., additional, Franco, E., additional, Stadlhuber, R.J., additional, Thumfart, L., additional, Croome, K., additional, Leeper, R., additional, Hernandez, R., additional, Livingstone, S., additional, Sapp, J., additional, Woodhall, D., additional, Alwayn, I., additional, Lam-McCulloch, J., additional, Balaa, F., additional, Jayaraman, S., additional, Quan, D., additional, Wei, A., additional, Guyatt, G., additional, Rekman, J.F., additional, Fairfull-Smith, R.J., additional, Mimeault, R., additional, Balaa, F.K., additional, Boehnert, M.S., additional, Bazerbachi, F., additional, Knaak, J.M., additional, Selzner, Nazia, additional, McGilvray, I.D., additional, Rotstein, O.D., additional, Adeyi, O.A., additional, Levy, G.A., additional, Grant, D.R., additional, Selzner, M., additional, Khalil, J. Abou, additional, Jamal, M., additional, Chaudhury, P., additional, Zogopoulos, G., additional, Petrakos, P., additional, Tchervenkov, J., additional, Barkun, J., additional, Jamal, M.H., additional, Hassanain, M., additional, Salman, A., additional, Tran, T., additional, Metrakos, P., additional, Groeschl, R.T., additional, Geller, D.A., additional, Marsh, J.W., additional, Gamblin, T.C., additional, Kim, P.T.W., additional, Greig, P. D., additional, Gallinger, S., additional, Wei, A.C., additional, Fischer, S.E., additional, Cleary, S.P., additional, Vogt, K.N., additional, Gray, D.K., additional, Aubin, J.M., additional, Fairfull-Smith, J.J., additional, Devitt, K.S., additional, Ramjaun, A., additional, Gallingher, S., additional, Alabbad, S., additional, Constantinos, D., additional, Hassanein, M., additional, Paraskevas, S., additional, Tanyingoh, D., additional, Dixon, E., additional, Kaplan, G.G., additional, Myers, R.P., additional, Howard, T.J., additional, Sutherland, F.R., additional, Zyromski, N.J., additional, Ball, C.G., additional, Coburn, N., additional, Law, C.H., additional, Greig, P., additional, Steven, G., additional, Baxter, N., additional, Fitch, M., additional, Wright, F., additional, Hochman, D.J., additional, Wirtzfeld, D.A., additional, Yaffe, C.S., additional, Yip, B., additional, Silverman, R., additional, McConnell, Y.J., additional, Temple, W.J., additional, Mack, L.A., additional, Bathe, O.F., additional, Scott, L., additional, Vandenberg, T., additional, Perera, F., additional, Potvin, K., additional, Chambers, A., additional, Loungnarath, R., additional, DeBroux, É., additional, Lavertu, S., additional, Donath, D., additional, Ayoub, J.-P., additional, Tehfé, M., additional, Richard, C., additional, Cornacchi, S.D., additional, Heller, B., additional, Farrokhyar, F., additional, Babra, M., additional, Lovrics, P.J., additional, Liberto, C., additional, Ghosh, S., additional, McLean, R., additional, Schiller, D., additional, Dumitra, S., additional, Duplisea, J., additional, Wexler, S., additional, Seely, J., additional, Smylie, J., additional, Knight, K., additional, Robertson, S., additional, Watters, J., additional, Zhang, T., additional, Arneout, A., additional, Wirtzfeld, D., additional, Yun, L., additional, Rakovitch, E., additional, Warner, E., additional, McCready, D., additional, Hodgson, N., additional, Quan, M.L., additional, Natarajan, B., additional, Govindarajan, V., additional, Thomas, P., additional, Loggie, B.W., additional, Brar, S., additional, Mahar, A., additional, Law, C., additional, Wiebe, M., additional, Baxter, N.N., additional, Gagliardi, A.R., additional, Kennedy, E.D., additional, Zih, F., additional, Rosario, C., additional, Dennis, J., additional, Gingras, A.-C., additional, Swallow, C., additional, Ko, Y.-J., additional, Rowsell, C., additional, Law, C.H.L., additional, Saskin, R., additional, Quan, M.-L., additional, Xie, M., additional, McLaughlin, K., additional, Marginean, C., additional, Moyana, T.N., additional, Boushey, R.P., additional, Auer, R.C., additional, Razik, R., additional, Haase, E., additional, Mathieson, A., additional, Smith, A.J., additional, Swallow, C.J., additional, Barnes, A., additional, Scheer, A.S., additional, Sabri, E., additional, Auer, R.A.C., additional, Reidel, K., additional, Trabulsi, N., additional, Meterissian, S., additional, Tamblyn, R., additional, Mayo, N., additional, Meguerditchian, A.N., additional, Brown, J.A., additional, Hamm, J., additional, Phang, P.T., additional, Raval, M.J., additional, Taylor, B., additional, Meguerditchian, A., additional, Hamm, J.D., additional, Patakfalvi, L., additional, Nassif, M., additional, Turcotte, R., additional, Nichols, A., additional, Riedel, K.E., additional, Winslade, N.E., additional, Grégoire, J.-P., additional, Abrahamovicz, M., additional, Megueerditchian, A., additional, Pasieka, J., additional, McMillan, C., additional, Lipa, J., additional, Snell, L., additional, Tomlinson, G., additional, Liberman, A.S., additional, Charlebois, P., additional, Stein, B., additional, Capretti, G., additional, Power, A., additional, Augustin, B., additional, Gamsa, A., additional, Kim, D.-J., additional, Feldman, L., additional, Vu, L., additional, Gown, A., additional, Jones, S., additional, Wiseman, S., additional, Jeong, D. Hyoun, additional, Hur, H., additional, Baik, S. Hyuk, additional, Kim, N. Kyu, additional, Faria, J., additional, Min, B. Soh, additional, Lumb, K., additional, Colquhoun, P., additional, Schmocker, S., additional, Huang, H., additional, Krzyzanowska, M. K., additional, Brierley, J., additional, Milot, H., additional, Lebrun, A., additional, Drolet, S., additional, Bouchard, A., additional, Grégoire, R.C., additional, Vuong, T., additional, DeBroux, E., additional, Liberman, S., additional, Powell, R., additional, Fowler, A., additional, Martin, K., additional, Pereira, G., additional, Einarsdottir, K., additional, Gagné, J.P., additional, Thibault, C., additional, Bouchard, P., additional, Gomes, T., additional, Musselman, R.P., additional, Mamdani, M., additional, Al-Omran, M., additional, AlObeed, O., additional, Armstrong, J.B.P., additional, Fergusson, D.A., additional, Forster, A.J., additional, Gomes, Tara, additional, Chan, B.P., additional, Al-Obaid, O., additional, Lim, D. Ro, additional, Gordon, P.H., additional, Lo, A., additional, Pinsk, I., additional, Brown, C., additional, Raval, M., additional, Cheng, H., additional, Wong, C., additional, Johnston, N., additional, Stephen, W., additional, Lindsay, L., additional, Forbes, S., additional, and Parry, N.G., additional

Published
2012
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34. A Multicenter Phase II Trial of Bortezomib in Patients with Previously Untreated Multiple Myeloma: Efficacy with Manageable Toxicity in Patients with Unexpectedly High Rates of Baseline Peripheral Neuropathy.

Author

Richardson, Paul, primary, Chanan-Khan, A., primary, Schlossman, R., primary, Munshi, N., primary, Wen, P., primary, Briemberg, H., primary, Kuter, D., primary, Oaklander, A., primary, Lonial, S., primary, Hassoun, H., primary, Doss, D., primary, Lunde, L., primary, Hayes, S., primary, McKenney, M., primary, Hande, K., primary, Lai, L., primary, Freeman, A., primary, Dinand, K., primary, McAlister, C., primary, Warren, D., primary, Collins, D., primary, Esseltine, D., primary, Amato, A., primary, and Anderson, K., primary

Published
2005
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36. BEST1-related autosomal dominant vitreoretinochoroidopathy: a degenerative disease with a range of developmental ocular anomalies.

Author

Vincent, A., McAlister, C., VandenHoven, C., and Héon, E.

Subjects
*GLAUCOMA diagnosis, *RETINAL degeneration, *RETINAL diseases, *EYE diseases, *OPHTHALMOLOGY
Abstract

PurposeTo describe the spectrum of phenotypic characteristics of BEST1-related autosomal dominant vitreoretinochoroidopathy (ADVIRC) in a family with p.V86M mutation.MethodsA retrospective review of the clinical, psychophysical, and electrophysiological phenotypes of six subjects with ADVIRC. Five family members were sequenced for mutations in the BEST1gene.ResultsA heterozygous change, p.V86M (c.256G>A), was identified in the BEST1gene in the three affected subjects tested, and was shown to segregate with the disease phenotype. The distance visual acuity ranged from 20/25 to absent perception of light. Clinical features observed included angle closure glaucoma (n=2), microcornea with shallow anterior chamber (n=1), iris dysgenesis (n=2), cataracts (n=4), classical peripheral concentric band of retinal hyperpigmentation (n=5), and optic nerve dysplasia (n=1). Full-field electroretinogram response amplitudes ranged from low normal (two cases; 27 and 32 years) to non-recordable (two cases; 42 and 63 years). Goldmann fields were normal in two (27 and 28 years) but were abnormal in two older subjects. Optical coherence tomography showed macular thinning in the proband, whereas his affected daughter had normal macular thickness. Electro-oculography showed borderline Arden's ratio (1.50) in the lone case tested (27 years).ConclusionADVIRC is a slowly progressive vitreoretinal degeneration that demonstrates marked intra-familial phenotypic variability. Optic nerve dysplasia and iris dysgenesis are novel observations that extend the ocular phenotype of ADVIRC. [ABSTRACT FROM AUTHOR]

Published
2011
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37. Pulmonary Exposure to Magnéli Phase Titanium Suboxides Results in Significant Macrophage Abnormalities and Decreased Lung Function

Author

Dylan K. McDaniel, Veronica M. Ringel-Scaia, Holly A. Morrison, Sheryl Coutermarsh-Ott, McAlister Council-Troche, Jonathan W. Angle, Justin B. Perry, Grace Davis, Weinan Leng, Valerie Minarchick, Yi Yang, Bo Chen, Sky W. Reece, David A. Brown, Thomas E. Cecere, Jared M. Brown, Kymberly M. Gowdy, Michael F. Hochella, and Irving C. Allen

Subjects
cytotoxicity, air pollution, nanoparticle, TixO2x−1, in vivo, environmental exposure, Immunologic diseases. Allergy, RC581-607
Abstract

Coal is one of the most abundant and economic sources for global energy production. However, the burning of coal is widely recognized as a significant contributor to atmospheric particulate matter linked to deleterious respiratory impacts. Recently, we have discovered that burning coal generates large quantities of otherwise rare Magnéli phase titanium suboxides from TiO2 minerals naturally present in coal. These nanoscale Magnéli phases are biologically active without photostimulation and toxic to airway epithelial cells in vitro and to zebrafish in vivo. Here, we sought to determine the clinical and physiological impact of pulmonary exposure to Magnéli phases using mice as mammalian model organisms. Mice were exposed to the most frequently found Magnéli phases, Ti6O11, at 100 parts per million (ppm) via intratracheal administration. Local and systemic titanium concentrations, lung pathology, and changes in airway mechanics were assessed. Additional mechanistic studies were conducted with primary bone marrow derived macrophages. Our results indicate that macrophages are the cell type most impacted by exposure to these nanoscale particles. Following phagocytosis, macrophages fail to properly eliminate Magnéli phases, resulting in increased oxidative stress, mitochondrial dysfunction, and ultimately apoptosis. In the lungs, these nanoparticles become concentrated in macrophages, resulting in a feedback loop of reactive oxygen species production, cell death, and the initiation of gene expression profiles consistent with lung injury within 6 weeks of exposure. Chronic exposure and accumulation of Magnéli phases ultimately results in significantly reduced lung function impacting airway resistance, compliance, and elastance. Together, these studies demonstrate that Magnéli phases are toxic in the mammalian airway and are likely a significant nanoscale environmental pollutant, especially in geographic regions where coal combustion is a major contributor to atmospheric particulate matter.

Published
2019
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47. Exploring the Challenges of Recruiting Older People for a Randomised Trial Assessing the Feasibility of Treating White Coat Hypertension in the UK General Practices: A Mixed-methods study.

Author

Mensah E, Ali K, Okorie M, Bremner S, McAlister C, Perry N, and Rajkumar C

Abstract

Introduction: There is a recognised association between white coat hypertension (WCH) and adverse cardiovascular outcomes in older adults. However, there is no consensus on the management of WCH in this group. The objective of the Hypertension in the Very Elderly Trial (HYVET-2) study was to assess the feasibility of randomising 100 patients > 75years with WCH from General Practice in the UK to treatment or usual care. The study did not randomise any patients. In this follow-up study, we sought to explore the reasons for not recruiting., Methods: Furthermore, using a mixed-methods study design, staff from 29 General Practice (GP) sites and the Clinical Research Network (CRN) in Kent, Surrey, and Sussex (KSS), UK, were sent an online questionnaire about local research facilities and infrastructure, and HYVET-2 study methodology and target population demographics., Results: Nineteen (19) individuals responded to the online questionnaires (15 primary care staff, 4 CRN staff). Moreover, using a framework approach, we identified six themes summarising challenges to HYVET-2 recruitment. These themes are established approaches of primary care towards managing WCH in older people, target patient demographics, study design complexity, patient- facing study documents, limited research resources in primary care, and identification of eligible patients using existing coding., Conclusion: Our experience showed that recruiting older people from primary care to a WCH study was not feasible. A national scoping survey amongst primary care physicians in the UK, as well as robust patient and public involvement (PPI) targeting older people with WCH, might improve recruitment in future studies addressing the management of WCH in older people., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Published
2024
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48. Neutralization, effector function and immune imprinting of Omicron variants.

Author

Addetia A, Piccoli L, Case JB, Park YJ, Beltramello M, Guarino B, Dang H, de Melo GD, Pinto D, Sprouse K, Scheaffer SM, Bassi J, Silacci-Fregni C, Muoio F, Dini M, Vincenzetti L, Acosta R, Johnson D, Subramanian S, Saliba C, Giurdanella M, Lombardo G, Leoni G, Culap K, McAlister C, Rajesh A, Dellota E Jr, Zhou J, Farhat N, Bohan D, Noack J, Chen A, Lempp FA, Quispe J, Kergoat L, Larrous F, Cameroni E, Whitener B, Giannini O, Cippà P, Ceschi A, Ferrari P, Franzetti-Pellanda A, Biggiogero M, Garzoni C, Zappi S, Bernasconi L, Kim MJ, Rosen LE, Schnell G, Czudnochowski N, Benigni F, Franko N, Logue JK, Yoshiyama C, Stewart C, Chu H, Bourhy H, Schmid MA, Purcell LA, Snell G, Lanzavecchia A, Diamond MS, Corti D, and Veesler D

Subjects
Animals, Cricetinae, Humans, Mice, Angiotensin-Converting Enzyme 2 immunology, Angiotensin-Converting Enzyme 2 metabolism, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal immunology, Cross Reactions, Immune Evasion, Membrane Fusion, Neutralization Tests, Mutation, Memory B Cells immunology, COVID-19 Vaccines immunology, Antibodies, Neutralizing chemistry, Antibodies, Neutralizing immunology, COVID-19 immunology, COVID-19 prevention & control, COVID-19 virology, SARS-CoV-2 classification, SARS-CoV-2 genetics, SARS-CoV-2 immunology
Abstract

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain 1 (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting., (© 2023. The Author(s).)

Published
2023
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49. Follow Up imaging After Left Atrial Appendage Occlusion-Something or Nothing and for How Long?

Author

Nestelberger T, Alfadhel M, McAlister C, and Saw J

Subjects
Humans, Follow-Up Studies, Treatment Outcome, Echocardiography, Transesophageal, Cardiac Catheterization methods, Atrial Appendage diagnostic imaging, Atrial Appendage surgery, Atrial Fibrillation diagnostic imaging, Atrial Fibrillation surgery, Atrial Fibrillation complications
Abstract

Routine postprocedural imaging with transesophageal echocardiography or cardiac computed tomography angiography is the most commonly used imaging modality for follow-up surveillance usually performed 1 to 6 months after the procedure. Imaging enables recognition of well-suited and sealed devices in the left atrial appendage as well as of potential harmful complications such as peri-device leaks, device-related thrombus, and device embolization, which may lead to further surveillance observation with recurrent imaging, reinitiation of oral anticoagulants, or additional interventional procedures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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50. Stroke Prevention With Left Atrial Appendage Closure in Patients With Atrial Fibrillation and Prior Intracranial Hemorrhage.

Author

Gilhofer TS, Nestelberger T, Kang M, Inohara T, Alfadhel M, McAlister C, Reddavid C, Samuel R, Field T, Teal P, Benevente O, Tsang M, and Saw J

Abstract

Background: Oral anticoagulation (OAC) is deemed a relative contraindication after intracranial hemorrhage (ICH) if the cause cannot be eliminated and the risk of recurrence is high. That leaves atrial fibrillation (AF) patients at high risk of thromboembolic events. Endovascular left atrial appendage closure (LAAC) can be an alternative to OAC for patients requiring stroke prevention., Methods: We performed a retrospective single-centre analysis of 138 consecutive ICH patients with nonvalvular AF and high stroke risk who underwent LAAC between 2010 and 2022 at Vancouver General Hospital. We report the baseline characteristics, procedural results, and follow-up data, comparing the observed stroke/transient ischemic attack (TIA) rate with the predicted event rate based on their CHA 2 DS 2 -VASc scores., Results: The average age was 76.1 ± 8.5 years; the mean CHA 2 DS 2 -VASc score was 4.4 ± 1.5; and the mean HAS-BLED score was 3.7 ± 0.9. The procedural success rate was 98.6%, and the complication rate was 3.6% with no periprocedural death, stroke, or TIA. The antithrombotic regimen post-LAAC consisted of short-term dual antiplatelet therapy (1-6 months) followed by aspirin alone for a minimum of 6 months in 86.2%. At mean follow-up of 14.7 ± 13.7 months, 9 deaths (6.5%, 7 cardiovascular, 2 noncardiovascular), 2 strokes (1.4%), and 1 TIA (0.7%) had occurred. The annualized observed stroke/TIA rate was 1.8%, which was lower than the adjusted predicted stroke rate of 7.0% (95% confidence interval: 4.8%-9.2%). Two patients (1.5%) suffered another ICH (both on aspirin monotherapy). One device-related thrombus (0.7%) was confirmed and treated with OAC without sequelae., Conclusion: Endovascular LAAC is a feasible alternative to OAC for stroke prevention in patients with nonvalvular AF and prior ICH., (© 2023 The Authors.)

Published
2023
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