Dynamics of DHA and EPA supplementation: incorporation into equine plasma, synovial fluid, and surfactant glycerophosphocholines.

INTRODUCTION: Horses with asthma or osteoarthritis frequently receive ω-3 fatty acid supplements. Docosahexaenoic (DHA; 22:6) and eicosapentaenoic (EPA; 20:5) acids are essential ω-3 fatty acid precursors of anti-inflammatory mediators and components of structural glycerophospholipids (GPL) that act as reservoirs of these fatty acids. Analysis of the incorporation of dietary DHA + EPA into GPL pools in different body compartments has not been undertaken in horses. OBJECTIVES: We undertook a detailed study of dietary supplementation with DHA + EPA in horses and monitored incorporation into DHA- and EPA-containing glycerophosphocholines (GPC) 38:5, 38:6, 40:5, and 40:6 in plasma, synovial fluid (SF), and surfactant. METHODS: Horses (n = 20) were randomly assigned to the supplement or control group and evaluated on days 0, 30, 60, and 90. GPC in plasma, SF, and surfactant were measured by high-resolution mass spectrometry with less than 3 ppm mass error. Validation of DHA and EPA incorporation into these GPC was conducted utilizing MS2 of the [M + Cl]- adducts of GPC. RESULTS: Dietary supplementation resulted in augmented levels of GPC 38:5, 38:6, 40:5, and 40:6 in all compartments. Maximum incorporation into GPCs was delayed until 60 days. Significant increases in the levels of GPC 38:5, 40:5, and 40:6, containing docosapentaenoic acid (DPA; 22:5), also was noted. CONCLUSIONS: DHA and EPA supplementation results in augmented storage pools of ω-3 essential fatty acids in SF and surfactant GPC. This has the potential to improve the ability of anti-inflammatory mechanisms to resolve inflammatory pathways in these critical compartments involved in arthritis and asthma.

Intraoperative discovery of melanosis coli during emergent bowel resection for perforation.

A patient was taken to the operating room with a presumptive diagnosis of necrotic small bowel and colon. During the procedure, it was noted that she had black mucosa throughout the colon. Several factors suggested viable colonic tissue, and the decision was made to not resect the colon as originally planned. Final pathology of the specimen would later reveal melanosis coli, an ultimately benign diagnosis. Further questioning of the patient found that she had taken a herbal laxative supplement containing several components which are known to cause melanosis coli. We hope that this case report will serve as a reminder to surgeons and clinicians to remember melanosis coli as a clinical entity when confronted with blackened or darkened colonic mucosa. On review of available literature, we identified other cases in which melanosis coli was discovered intraoperatively, and we propose a number of factors to support intraoperative decision making.

Making the Correct Diagnosis in Thrombotic Microangiopathy: A Narrative Review.

PURPOSE OF REVIEW: Thrombotic microangiopathy (TMA) is suspected in patients presenting with thrombocytopenia and evidence of a microangiopathic hemolytic anemia. Patients with TMA can be critically ill, so rapid and accurate identification of the underlying etiology is essential. Due to better insights into pathophysiology and causes of TMA, we can now categorize TMAs as thrombotic thrombocytopenic purpura, postinfectious (mainly Shiga toxin-producing Escherichia coli-induced) hemolytic uremic syndrome (HUS), TMA associated with a coexisting condition, or atypical HUS (aHUS). We recognized an unmet need in the medical community to guide the timely and accurate identification of TMA, the selection of tests to clarify its etiology, and the sequence of steps to initiate treatment. SOURCES OF INFORMATION: Key published studies relevant to the identification, classification, and treatment of TMAs in children or adults. These studies were obtained through literature searches conducted with PubMed or based on the prior knowledge of the authors. METHODS: This review is the result of a consultation process that reflects the consensus of experts from Canada, the United States, and the United Arab Emirates. The members represent individuals who are clinicians, researchers, and teachers in pediatric and adult medicine from the fields of hematology, nephrology, and laboratory medicine. Authors, through an iterative review process identified and synthesized information from relevant published studies. KEY FINDINGS: Thrombotic thrombocytopenic purpura occurs in the setting of insufficient activity of the von Willebrand factor protease known as ADAMTS13. Shiga toxin-producing Escherichia coli-induced hemolytic uremic syndrome, also known as "typical" HUS, is caused by gastrointestinal infections with bacteria that produce Shiga toxin (initially called verocytotoxin). A variety of clinical conditions or drug exposures can trigger TMA. Finally, aHUS occurs in the setting of inherited or acquired abnormalities in the alternative complement pathway leading to dysregulated complement activation, often following a triggering event such as an infection. It is possible to break the process of etiological diagnosis of TMA into 2 distinct steps. The first covers the initial presentation and diagnostic workup, including the processes of identifying the presence of TMA, appropriate initial tests and referrals, and empiric treatments when appropriate. The second step involves confirming the etiological diagnosis and moving to definitive treatment. For many forms of TMA, the ultimate response to therapies and the outcome of the patient depends on the rapid and accurate identification of the presence of TMA and then a standardized approach to seeking the etiological diagnosis. We present a structured approach to identifying the presence of TMA and steps to identifying the etiology including standardized lab panels. We emphasize the importance of early consultation with appropriate specialists in hematology and nephrology, as well as identification of whether the patient requires plasma exchange. Clinicians should consider appropriate empiric therapies while following the steps we have recommended toward definitive etiologic diagnosis and management of the TMA. LIMITATIONS: The evidence base for our recommendations consists of small clinical studies, case reports, and case series. They are generally not controlled or randomized and do not lend themselves to a stricter guideline-based methodology or a Grading of Recommendations Assessment, Development and Evaluation (GRADE)-based approach.

JUSTIFICATION: La microangiopathie thrombotique (MAT) est suspectée chez les patients présentant une thrombocytopénie et la preuve d'une anémie hémolytique microangiopathique (AHMA). Les patients atteints de MAT peuvent être gravement malades, il est donc essentiel de déterminer rapidement et précisément l'étiologie sous-jacente. Grâce à une meilleure connaissance de la physiopathologie et des causes de la MAT, nous pouvons désormais classer les MAT par catégorie: purpura thrombocytopénique thrombotique (PTT), syndrome hémolytique urémique post-infectieux (SHU) principalement induit par STEC (Escherichia coli produisant la toxine Shiga), ou MAT associée à une affection coexistante ou à un SHU atypique (SHUa). Nous avons constaté un besoin dans la communauté médicale pour guider à la fois la détection rapide et précise de la MAT, la sélection des tests pour clarifier son étiologie et la séquence des étapes menant à l'initiation du traitement. SOURCES: Des recherches documentaires sur PubMed et les connaissances antérieures des auteurs ont permis de colliger les principales études publiées portant sur la détection, la classification et le traitement de la MAT chez les enfants ou les adultes. MÉTHODOLOGIE: Cet examen est le résultat d'un processus de consultation qui reflète le consensus des experts du Canada, des États-Unis et des Émirats arabes Unis. Les membres représentent des cliniciens, des chercheurs et des enseignants en médecine pédiatrique et adulte dans les domaines de l'hématologie, de la néphrologie et de la médecine de laboratoire. Les auteurs, par le biais d'un processus d'examen itératif, ont colligé et synthétisé l'information provenant des études publiées jugées pertinentes. PRINCIPAUX RÉSULTATS: Le PTT survient lors d'une activité insuffisante de la protéase du facteur Willebrand connue sous le nom d'ADAMTS13. Le SHU-STEC, aussi appelé SHU « typique ¼, est causé par des infections gastro-intestinales dues à des bactéries produisant la toxine Shiga (initialement appelée vérocytotoxine). Plusieurs états pathologiques ou expositions à des médicaments peuvent déclencher la MAT. Quant au SHU atypique (SHUa), il survient en présence d'anomalies héréditaires ou acquises de la voie du complément alternatif qui mènent à un dérèglement de l'activation du complément, souvent à la suite d'un événement déclencheur comme une infection. On peut diviser le processus de diagnostic étiologique de la MAT en deux étapes distinctes. La première couvre la présentation initiale et le diagnostic, y compris les processus de détection de la MAT, les tests initiaux et aiguillages appropriés, ainsi que les traitements empiriques si nécessaire. La deuxième étape consiste à confirmer le diagnostic étiologique et à procéder au traitement définitif. Pour de nombreuses formes de MAT, la réponse ultime aux traitements et le résultat du patient dépendent de la détection rapide et précise de la MAT et ensuite, d'une approche standardisée pour la recherche du diagnostic étiologique. Nous présentons une approche structurée pour détecter la présence de MAT ainsi qu'une démarche pour rechercher l'étiologie, y compris des tableaux de laboratoire normalisés. Nous soulignons l'importance d'une consultation précoce avec les spécialistes appropriés en hématologie et en néphrologie, et de la détermination d'un éventuel besoin d'échange de plasma (PLEX) pour le patient. Les cliniciens devraient envisager les traitements empiriques appropriés tout en suivant la démarche que nous recommandons pour le diagnostic étiologique définitif et la gestion de la MAT. LIMITES: La base factuelle de nos recommandations est constituée de petites études cliniques, de rapports de cas et de séries de cas. Ces études ne sont généralement pas contrôlées ou randomisées et ne se prêtent pas à une méthodologie plus stricte basée sur des lignes directrices ni à une approche fondée sur le GRADE (Grading of Recommendations Assessment, Development and Evaluation).

Blood-brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder of systemic microthrombosis and organ ischemia. The etiology of chronic cerebrovascular outcomes in iTTP survivors is largely unknown. In this pilot study, we measured blood-brain barrier (BBB) permeability in patients with iTTP at the start of remission and 6 months later. This prospective pilot study included 7 adult patients with incident iTTP. Eligibility criteria included ADAMTS13 activity < 10% and detectable inhibitor at diagnosis. Patients were recruited from London Health Sciences Centre in Canada (2017-2019) within 3 days of hospital admission and followed for 6 months after remission (defined as normalization of platelet count and lactate dehydrogenase with no clinical signs or symptoms of microvascular injury for more than 30 days after the last plasma exchange). All patients had cerebral computed tomography perfusion scans with BBB permeability surface product measurements. Patients (5 women, 2 men) had a mean age of 48 years (range, 21-77 years). At diagnosis, patients had a mean platelet count of 22 (standard deviation [SD], 25) × 109/L. At the start of remission, mean BBB permeability surface product was 0.91 (0.30) mL/min/100 g. Six months later, the mean permeability surface product was 0.56 (0.22) mL/min/100 g, with a mean difference of -0.312 mL/min/100 g (95% confidence interval: -0.4729 to -0.1510; P = .0032). In this pilot study of patients with iTTP, pathologically increased BBB permeability was evident, and although there was some improvement, this persisted 6 months after remission. Future work will explore the chronicity of these findings and their clinical implications.