COVID-19-associated coagulopathy in children: A multicenter observational cohort study.

SARS-CoV-2 infection (coronavirus disease 2019 [COVID-19]) induces a stark procoagulant state, with many hospitalized adults developing thrombosis despite prophylactic anticoagulation. This study aimed to characterize hemostatic parameters and associated clinical outcomes of COVID-19, such as thrombosis and bleeding, in children and to assess thromboprophylaxis use. This multicenter observational cohort study included 79 patients aged up to 18 years admitted to all pediatric hospitals in Québec, Canada, with SARS-CoV-2 infection during a 5-month period. D-dimers were elevated in 18/19 patients (94.7%) and fibrinogen in 15/26 patients (60%). Eleven patients (13.9%) received anticoagulant thromboprophylaxis. One thrombotic event and one major bleed were observed.

Management of acquired hemophilia A: Review of current evidence.

Acquired hemophilia A (AHA) is a rare acquired bleeding disorder caused by autoantibodies against autologous factor VIII (FVIII). It is a disease that most commonly affects the elderly, but it has been described in children and during the post-partum period. It is idiopathic in 50% of cases and is associated with autoimmune disease, malignancy, pregnancy, infection or certain medications in the other 50%. The diagnosis should be suspected in patients with an isolated prolonged aPPT without previous personal or familial bleeding history. Treating the bleeding and eradication of the inhibitor is the mainstay of treatment. The first line of treatment for acute bleeding is the use of bypassing agents. The most commonly used method for eradicating the inhibitor is immunosuppression, namely corticosteroids alone or in combination with cyclophosphamide. This review summarises current knowledge and reviews management options and guidelines.

Management of acquired von Willebrand syndrome.

Acquired von Willebrand syndrome (AVWS) is a rare acquired bleeding disorder that resembles von Willebrand disease by its clinical symptoms and laboratory findings, but differs by its negative personal and family history of bleeding diathesis. AVWS is mostly seen in the elderly, but it has been described in children, often in those with congenital heart disease and Wilms tumor. It is most commonly associated with lymphoproliferative, myeloproliferative, cardio-vascular, or autoimmune diseases, solid tumors, and certain drugs. The diagnosis should be suspected in a patient who is known for one of these underlying conditions and who presents with new onset of bleeding or who will be undergoing an invasive procedure. Treatment of the underlying condition, when possible, usually results in correction of AVWS. When acute bleeding occurs or the underlying condition is not treated, emphasis should be put on control and prevention of bleeding. Many options are available. DDAVP is the first line of treatment for bleeding. vWF concentrates are used to treat bleeding that is unresponsive to DDAVP and as prophylaxis before procedures. This review summarises current knowledge and reviews the different management options for bleeding.

Quality indicators for paediatric palliative care.

OBJECTIVES: To apply quality indicators for paediatric palliative care and evaluate performance in one service provision area. METHODS: After institutional review board approval, medical records were abstracted for well-defined and measurable quality indicators for children with chronic complex conditions (CCCs) between January 2006 and December 2011 (n=50) at a university medical centre. RESULTS: Of the 50 children with a CCC (mean age 64 months, 48% female), 39 (78%) died in hospital, 11 (22%) died at home and 13 (26%) were <1 month of age. In the final month of their life, 10 patients (20%) required an unplanned visit to the emergency department and seven (14%) were admitted. Only four patients (8%) were admitted for >14 days in their final month of life. Goals of care were addressed in a timely manner 60% of the time. An invasive procedure was performed in the final month of life in 27 (44%) patients. Bereavement follow-up was offered to 25 (50%) families. A palliative care consultant was involved with 17 (34%) patients. Palliative care was associated with less frequent invasive procedures in the final month of life and more frequent documentation of the preferred place of death. CONCLUSION: Performance on these particular quality indicators was unsatisfactory across a diverse group of children with CCCs, indicating important opportunities for improvement. Methods used to improve the quality of other aspects of paediatric care, including emphasis on efficient work systems, practical tools and interdisciplinary teamwork, should be used for ensuring delivery of high-quality palliative care.

OBJECTIFS: Mettre en application des indicateurs de qualité en soins palliatifs pédiatriques et en évaluer l'exécution dans une région de prestation des services. MÉTHODOLOGIE: Après avoir obtenu l'approbation du conseil de révision de l'établissement, les chercheurs ont résumé les dossiers médicaux d'un centre de santé universitaire de janvier 2006 à décembre 2011. Ils visaient ainsi établir des indicateurs de qualité bien définis et mesurables auprès d'enfants ayant des problèmes de santé complexes et chroniques (PSCC; n=50). RÉSULTATS: Sur les 50 enfants ayant des PSCC (âge moyen de 64 mois, 48 % de filles), 39 (78 %) sont décédés à l'hôpital, 11 (22 %) sont décédés à la maison et 13 (26 %) avaient moins d'un mois. Au cours du dernier mois de leur vie, dix patients (20 %) ont dû se rendre à la salle d'urgence sans l'avoir planifié et sept (14 %) ont été hospitalisés. Seulement quatre patients (8 %) ont été hospitalisés plus de 14 jours pendant le dernier mois de leur vie. Dans 60 % des cas, les objectifs des soins ont été abordés dans un délai convenable. Au cours du dernier mois de leur vie, 27 patients (44 %) ont subi une intervention invasive. Par ailleurs, 25 familles (50 %) se sont fait offrir un suivi du deuil, et un consultant en soins palliatifs est intervenu auprès de 17 patients (34 %). Les soins palliatifs favorisaient la diminution du nombre d'interventions invasives pendant le dernier mois de vie et l'augmentation de la consignation du lieu privilégié pour mourir. CONCLUSION: L'exécution de ces indicateurs de qualité était insatisfaisante dans un groupe diversifié de patients ayant des PSCC, ce qui est indicateur d'importantes possibilités d'amélioration. Il faudrait recourir aux méthodes utilisées pour améliorer la qualité d'autres aspects des soins pédiatriques, en s'attardant à des systèmes de travail, des outils pratiques et un travail d'équipe interdisciplinaire efficaces, pour assurer la prestation de soins palliatifs de qualité.

Canadian Pediatric Neuro-Oncology Standards of Practice.

Primary CNS tumors are the leading cause of cancer-related death in pediatrics. It is essential to understand treatment trends to interpret national survival data. In Canada, children with CNS tumors are treated at one of 16 tertiary care centers. We surveyed pediatric neuro-oncologists to create a national standard of practice to be used in the absence of a clinical trial for seven of the most prevalent brain tumors in children. This allowed description of practice across the country, along with a consensus. This had a multitude of benefits, including understanding practice patterns, allowing for a basis to compare in future research and informing Health Canada of the current management of patients. This also allows all children in Canada to receive equivalent care, regardless of location.

Author Correction: Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome.

In the version of this article originally published, the main-text sentence "In three patients of European ancestry, we identified the germline variant encoding p.Ile97Met in TIM-3, which was homozygous in two (P12 and P13) and heterozygous in one (P15) in the germline but with no TIM-3 plasma membrane expression in the tumor" misstated the identifiers of the two homozygous individuals, which should have been P13 and P14. The error has been corrected in the HTML, PDF and print versions of the paper.

Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL), a non-Hodgkin lymphoma, can be associated with hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune activation that adversely affects survival1,2. T cell immunoglobulin mucin 3 (TIM-3) is a modulator of immune responses expressed on subgroups of T and innate immune cells. We identify in ~60% of SPTCL cases germline, loss-of-function, missense variants altering highly conserved residues of TIM-3, c.245A>G (p.Tyr82Cys) and c.291A>G (p.Ile97Met), each with specific geographic distribution. The variant encoding p.Tyr82Cys TIM-3 occurs on a potential founder chromosome in patients with East Asian and Polynesian ancestry, while p.Ile97Met TIM-3 occurs in patients with European ancestry. Both variants induce protein misfolding and abrogate TIM-3's plasma membrane expression, leading to persistent immune activation and increased production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß, promoting HLH and SPTCL. Our findings highlight HLH-SPTCL as a new genetic entity and identify mutations causing TIM-3 alterations as a causative genetic defect in SPTCL. While HLH-SPTCL patients with mutant TIM-3 benefit from immunomodulation, therapeutic repression of the TIM-3 checkpoint may have adverse consequences.