Hyperacute multi-organ thromboembolic storm in COVID-19: a case report.

Acute viral pneumonia, hypoxemic respiratory failure and severe inflammatory response are hallmarks of severe coronavirus disease 2019 (COVID-19). The COVID-19-associated inflammatory state may further lead to symptomatic thromboembolic complications despite prophylaxis. We report a 66-year-old female patient with post-mortem diagnosis of COVID-19 who presented progressive livedo racemosa, acute renal failure and myocardial injury, as well as an absence of respiratory symptoms. Transthoracic echocardiography showed severe spontaneous echo contrast in the right cardiac chambers and right-sided cardiac overload presumed to result from pulmonary microvascular thrombosis or embolism. D-dimer levels were increased. The patient developed an acute ischemic stroke and died 2 days following presentation despite therapeutic anticoagulation. Her predominantly thromboembolic presentation supports the concept of coronavirus infection of endothelial cells and hypercoagulability, or COVID-19 endotheliitis. The case we report highlights that COVID-19-associated hyperacute multi-organ thromboembolic storm may precede or present disproportionately to respiratory involvement.

Role of Bacillus subtilis Spore Core Water Content and pH in the Accumulation and Utilization of Spores' Large 3-Phosphoglyceric Acid Depot, and the Crucial Role of This Depot in Generating ATP Early during Spore Germination.

The development of Bacillus spore cores involves the accumulation of 3-phosphoglycerate (3PGA) during sporulation, following core acidification to ~6.4, and before decreases in core water content occur due to Ca-dipicolinc acid (CaDPA) uptake. This core acidification inhibits phosphoglycerate mutase (PGM) at pH 6.4, allowing 3PGA accumulation, although PGM is active at pH 7.4. Spores' 3PGA is stable for months at 4 °C and weeks at 37 °C. However, in wild-type spore germination, increases in core pH to 7.5−8 and in core water content upon CaDPA release and cortex peptidoglycan hydrolysis allow for rapid 3PGA catabolism, generating ATP; indeed, the earliest ATP generated following germination is from 3PGA catabolism. The current work found no 3PGA in those Bacillus subtilis spores that do not accumulate CaDPA during sporulation and have a core pH of ~7.4. The ATP production in the germination of 3PGA-less spores in a poor medium was minimal, and the germinated spores were >99% dead. However, the 3PGA-replete spores that germinated in the poor medium accumulated >30 times more ATP, and >70% of the germinated spores were found to be alive. These findings indicate why 3PGA accumulation during sporulation (and utilization during germination) in all the Firmicute spores studied can be crucial for spore revival due to the generation of essential ATP. The latter finding further suggests that targeting PGM activity during germination could be a novel way to minimize the damaging effects of spores.

Colour Doppler ultrasound and the giant cell arteritis probability score for the diagnosis of giant cell arteritis: a Canadian single-centre experience.

OBJECTIVES: The aim was to compare the accuracy of colour Doppler ultrasonography (CDUS) and temporal artery biopsy (TAB) to establish the final diagnosis of GCA and to determine how the GCA probability score (GCAPS) performs as a risk stratification tool. METHODS: Descriptive statistics were performed on a retrospective cohort of patients referred to our vasculitis referral centre between 1 July 2017 and 1 October 2020 for suspected GCA. CDUS, TAB, centre-specific TAB (vasculitis centre vs referring hospitals) and GCAPS were compared against the final diagnosis of GCA as determined by a GCA expert; CDUS was also compared with TAB results. RESULTS: Data from 198 patients were included: 60 patients with GCA and 138 patients without GCA. Sixty-two patients had a TAB. Using the final diagnosis by a GCA expert as a reference, the sensitivity, specificity, positive predictive value and negative predictive value were 93.3%, 98.5%, 96.6% and 97.1% for CDUS and 69.2%, 100%, 100% and 81.8% for TAB, respectively. The false-negative rate was 6.7% for CDUS and 30.8% for TAB. False-negative TAB mostly occurred when performed in referring hospitals (57.1%) as opposed to our vasculitis centre (21.1%). With a cut-off at 9.5 points, sensitivity for GCAPS was 98.3% and specificity 74.3%. CONCLUSION: CDUS of the temporal and axillary arteries showed a high sensitivity and specificity and helped to diagnose GCA in patients with negative TAB. We validated that GCAPS is a useful clinical tool, with a score of <9.5 making the diagnosis of GCA improbable.

Atorvastatin-induced necrotizing autoimmune myositis: An emerging dominant entity in patients with autoimmune myositis presenting with a pure polymyositis phenotype.

The general aim of this study was to evaluate the disease spectrum in patients presenting with a pure polymyositis (pPM) phenotype. Specific objectives were to characterize clinical features, autoantibodies (aAbs), and membrane attack complex (MAC) in muscle biopsies of patients with treatment-responsive, statin-exposed necrotizing autoimmune myositis (NAM). Patients from the Centre hospitalier de l'Université de Montréal autoimmune myositis (AIM) Cohort with a pPM phenotype, response to immunosuppression, and follow-up ≥3 years were included. Of 17 consecutive patients with pPM, 14 patients had a NAM, of whom 12 were previously exposed to atorvastatin (mean 38.8 months). These 12 patients were therefore suspected of atorvastatin-induced AIM (atorAIM) and selected for study. All had aAbs to 3-hydroxy-3-methylglutaryl coenzyme A reductase, and none had overlap aAbs, aAbs to signal recognition particle, or cancer. Three stages of myopathy were recognized: stage 1 (isolated serum creatine kinase [CK] elevation), stage 2 (CK elevation, normal strength, and abnormal electromyogram [EMG]), and stage 3 (CK elevation, proximal weakness, and abnormal EMG). At diagnosis, 10/12 (83%) patients had stage 3 myopathy (mean CK elevation: 7247 U/L). The presenting mode was stage 1 in 6 patients (50%) (mean CK elevation: 1540 U/L), all of whom progressed to stage 3 (mean delay: 37 months) despite atorvastatin discontinuation. MAC deposition was observed in all muscle biopsies (isolated sarcolemmal deposition on non-necrotic fibers, isolated granular deposition on endomysial capillaries, or mixed pattern). Oral corticosteroids alone failed to normalize CKs and induce remission. Ten patients (83%) received intravenous immune globulin (IVIG) as part of an induction regimen. Of 10 patients with ≥1 year remission on stable maintenance therapy, IVIG was needed in 50%, either with methotrexate (MTX) monotherapy or combination immunosuppression. In the remaining patients, MTX monotherapy or combination therapy maintained remission without IVIG. AtorAIM emerged as the dominant entity in patients with a pPM phenotype and treatment-responsive myopathy. Isolated CK elevation was the mode of presentation of atorAIM. The new onset of isolated CK elevation on atorvastatin and persistent CK elevation on statin discontinuation should raise early suspicion for atorAIM. Statin-induced AIM should be included in the differential diagnosis of asymptomatic hyperCKemia. Three patterns of MAC deposition, while nonpathognomonic, were pathological clues to atorAIM. AtorAIM was uniformly corticosteroid resistant but responsive to IVIG as induction and maintenance therapy.

CanVasc Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitides.

OBJECTIVE: The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties and researchers with expertise in vasculitis. One of its aims is to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. METHODS: Diagnostic and therapeutic questions were developed based on the results of a national needs assessment survey. A systematic review of existing non-Canadian recommendations and guidelines for the diagnosis and management of AAV and studies of AAV published after the 2009 European League Against Rheumatism/European Vasculitis Society recommendations (publication date: January 2009) until November 2014 was performed in the Medline database, Cochrane library, and main vasculitis conference proceedings. Quality of supporting evidence for each therapeutic recommendation was graded. The full working group as well as additional reviewers, including patients, reviewed the developed therapeutic recommendations and nontherapeutic statements using a modified 2-step Delphi technique and through discussion to reach consensus. RESULTS: Nineteen recommendations and 17 statements addressing general AAV diagnosis and management were developed, as well as appendices for practical use, for rheumatologists, nephrologists, respirologists, general internists, and all other healthcare professionals more occasionally involved in the management of patients with AAV in community and academic practice settings. CONCLUSION: These recommendations were developed based on a synthesis of existing international guidelines, other published supporting evidence, and expert consensus considering the Canadian healthcare context, with the intention of promoting best practices and improving healthcare delivery for patients with AAV.

Development of Canadian Recommendations for the Management of ANCA-Associated Vasculitides: Results of the National Needs Assessment Questionnaire.

OBJECTIVES: To study variations in Canadian clinical practice patterns for the management of ANCA-associated vasculitis (AAV) and identify points to consider for the development of national recommendations. MATERIAL AND METHODOLOGY: A 30-item needs assessment questionnaire was sent to all members of the Canadian Vasculitis network (CanVasc), Canadian Rheumatology Association (CRA), Canadian Thoracic Society (CTS) and Canadian Society of Nephrology (CSN). Respondent characteristics, practice patterns, concerns and expectations were analyzed. RESULTS: Among 132 physicians who followed at least 1 vasculitis patient and responded to the survey, 39% stated that they felt confident in their management of AAV. Several variations in practice were observed regarding diagnostic procedure, induction and maintenance treatments and use of biologics; some were due to logistic constraints (difficulties in access to some specific tests, drugs or care; lack of health care coverage for the costs). The top 5 topics for which recommendations are expected involve treatment for remission induction, maintenance, refractory disease, and relapse as well as biologics. CONCLUSION: Practice variations identified in this needs assessment survey will serve to formulate key questions for the development of CanVasc recommendations.