Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement Presenting with Polycythemia Vera and T-cell Acute Lymphoblastic Leukemia.

Myeloid/lymphoid neoplasm with fibroblast growth factor 1 rearrangements (MLN-FGFR1) represents a rare group of hematologic neoplasms, with approximately 100 cases reported to date. A 69-year-old woman with a history of polycythemia and leukocytosis, with negative molecular testing for JAK2, CALR, and MPL, presented with diffuse adenopathy. A lymph node (LN) biopsy revealed effacement by T-lymphoblasts, consistent with T-cell acute lymphoblastic lymphoma (T-ALL). A staging bone marrow (BM) biopsy demonstrated trilineage hyperplasia, which, taken together with the patient's elevated hemoglobin and low serum erythropoietin level, fulfilled diagnostic criteria for polycythemia vera. Karyotype and fluorescence in situ hybridization on both the BM and LN demonstrated a FGFR1 rearrangement due to t(8;13), consistent with MLN-FGFR1. Whole genome sequencing on the LN additionally identified a pathogenic frameshift mutation of ASXL1 NC_000020.11:g32434646dup NM_015338.6(ASXL1):c.1934dup p.(Gly646Trpfs) predicted to result in loss of protein function, a finding also observed in 8.1% of BM reads. Both the BM and LN harbored missense variants in HDAC4 NM_001378414.1(HDAC4):c.[2763G>A]; [2763=] p.(Met921Ile) and CHEK2 NM_007194.4(CHEK2):c.[538C>T];[538=] p.(Arg180Cys), with an unknown significance. Despite initial response to Mini-CVD + venetoclax, the patient subsequently experienced rapid clinical deterioration and death. We report the second case of MLN-FGFR1 with an ASXL1 mutation and the first case with HDAC4 and CHEK2 variants.

DIRECTIVE CLINIQUE CONJOINTE DE LA SOGC ET DE LA SCP: Directive clinique no 424 : Prise en charge du cordon ombilical chez le nourrisson prématuré ou à terme.

Objectif: Évaluer l'effet du clampage retardé du cordon et de la traite du cordon ombilical sur les risques de mortalité et de morbidité maternelles et néonatales en contexte de grossesses monofœtale ou gémellaire. Population cible: Femmes enceintes dont la grossesse monofœtale ou gémellaire est à terme ou avant terme. Bénéfices risques et coûts: Chez les prématurés de grossesse monofœtale, le clampage retardé de 60 à 120 secondes idéalement, mais d'au moins 30 secondes, réduit le risque de mortalité et de morbidité. Chez les jumeaux prématurés, le clampage retardé est associé à certains bénéfices. Chez les nourrissons de grossesse monofœtale à terme, le clampage retardé de 60 secondes améliore les paramètres hématologiques. Chez les grands prématurés, la traite du cordon ombilical augmente le risque d'hémorragie intraventriculaire. Données probantes: Une recherche a été effectuée au moyen des bases de données Medline, PubMed, Embase et Cochrane Library, de leur création jusqu'à mars 2020, à partir de termes MeSH et de mot-clés liés au clampage retardé du cordon et à la traite du cordon ombilical. Le présent document est un résumé des données probantes et non pas une revue méthodologique. Méthodes de validation: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]).

JOINT SOGC-CPS CLINICAL PRACTICE GUIDELINE: Guideline No. 424: Umbilical cord management in preterm and term infants.

Objective: To assess the impact of deferred (delayed) cord clamping (DCC) and umbilical cord milking in singleton and twin gestations on maternal and infant mortality and morbidity. Target Population: Women who are pregnant with preterm or term singletons or twins. Benefits Harms and Costs: In preterm singletons, DCC for (ideally) 60 to 120 seconds, but at least for 30 seconds, reduces infant risk of mortality and morbidity. DCC in preterm twins is associated with some benefits. In term singletons, DCC for 60 seconds improves hematological parameters. In very preterm infants, umbilical cord milking increases risk for intraventricular hemorrhage. Evidence: Searches of Medline, PubMed, Embase, and the Cochrane Library from inception to March 2020 were undertaken using Medical Subject Heading (MeSH) terms and key words related to deferred cord clamping and umbilical cord milking. This document represents an abstraction of the evidence rather than a methodological review. Validation Methods: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations).

Guideline No. 424: Umbilical Cord Management in Preterm and Term Infants.

OBJECTIVE: To assess the impact of deferred (delayed) cord clamping (DCC) and umbilical cord milking in singleton and twin gestations on maternal and infant mortality and morbidity. TARGET POPULATION: People who are pregnant with preterm or term singletons or twins. BENEFITS, HARMS, AND COSTS: In preterm singletons, DCC for (ideally) 60 to 120 seconds, but at least for 30 seconds, reduces infant risk of mortality and morbidity. DCC in preterm twins is associated with some benefits. In term singletons, DCC for 60 seconds improves hematological parameters. In very preterm infants, umbilical cord milking increases risk for intraventricular hemorrhage. EVIDENCE: Searches of Medline, PubMed, Embase, and the Cochrane Library from inception to March 2020 were undertaken using Medical Subject Heading (MeSH) terms and key words related to deferred cord clamping and umbilical cord milking. This document represents an abstraction of the evidence rather than a methodological review. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED USERS: Maternity and newborn care providers.

Directive clinique no 424 : Prise en charge du cordon ombilical chez le nourrisson prématuré ou à terme.

OBJECTIF: Évaluer l'effet du clampage retardé du cordon et de la traite du cordon ombilical sur les risques de mortalité et de morbidité maternelles et néonatales en contexte de grossesses monofœtale ou gémellaire. POPULATION CIBLE: Femmes enceintes dont la grossesse monofœtale ou gémellaire est à terme ou avant terme. BéNéFICES, RISQUES ET COûTS: Chez les prématurés de grossesse monofœtale, le clampage retardé de 60 à 120 secondes idéalement, mais d'au moins 30 secondes, réduit le risque de mortalité et de morbidité. Chez les jumeaux prématurés, le clampage retardé est associé à certains bénéfices. Chez les nourrissons de grossesse monofœtale à terme, le clampage retardé de 60 secondes améliore les paramètres hématologiques. Chez les grands prématurés, la traite du cordon ombilical augmente le risque d'hémorragie intraventriculaire. DONNéES PROBANTES: Une recherche a été effectuée au moyen des bases de données Medline, PubMed, Embase et Cochrane Library, de leur création jusqu'à mars 2020, à partir de termes MeSH et de mots clés liés au clampage retardé du cordon et à la traite du cordon ombilical. Le présent document est un résumé des données probantes et non pas une revue méthodologique. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CIBLES: Fournisseurs de soins de maternité et néonataux.

Is 5q deletion in de novo Acute Myelogenous Leukemia (AML) with excess blasts a surrogate marker for the cryptic t(7;21)(p22;q22)? A case report and review of literature.

Although the 5q- syndrome is common in both de novo and treatment related myelodysplastic syndrome (MDS) and the World Health Organization defined 5q- syndrome as a specific type of MDS, it is less common in acute myelogenous leukemia (AML). Recently, it was suggested that AML with diploidy/tetraploidy and/or 5q alterations may be associated with the cryptic translocation, t(7;21)(p22;q22) resulting in RUNX1-USP42 gene fusion and this association may have been underestimated. Here, we report another case of de novo AML with cryptic t(7;21)(p22;q22) associated with a 5q deletion.

Bi-allelic amplification of ATM gene in blastoid variant of mantle cell lymphoma: a novel mechanism of inactivation due to chromoanagenesis?

BACKGROUND: Mantle cell lymphoma (MCL) is derived from naïve CD5+ B-cells with the cytogenetic hallmark translocation 11;14. The presence of additional abnormalities is associated with blastoid variants in MCL (BMCL) and confers a poor prognosis. Many of these tumors also show deletion or loss of heterozygosity (LOH) of the ATM gene and biallelic ATM inactivation show significantly higher chromosomal imbalances. CASE PRESENTATION: Here we report a 52 year-old male who presented to the clinic with worsening dyspnea, fever, chills, diffuse lymphadenopathy, splenomegaly and leukocytosis with blastoid cells circulating in blood. The bone marrow aspirate showed about 40% abnormal blast-looking cells and biopsy revealed a remarkable lymphoid infiltrate. The patient was diagnosed with blastoid variant mantle cell lymphoma (BMCL). Chromosome analysis on bone marrow showed a complex karyotype. FISH analysis from B-cell lymphoma panel showed bi-allelic amplification of ATM gene. Other abnormalities were present including CCND1/IGH fusion, confirming the MCL diagnosis, in addition to RB1 and p53 deletion. High resolution SNP-microarray studies showed complex copy number changes, especially on chromosomes 7 and 11, consistent with chromoanagenesis. Microarray studies also showed LOH at the ATM locus indicating the amplification seen on FISH is not biallelic. CONCLUSION: To the best of our knowledge, ATM gene amplification is not previously reported in BMCL and our case suggests a novel mechanism of ATM inactivation caused by chromoanagenesis resulting in mutant allele specific imbalance with copy number gain.

No. 396-Fetal Health Surveillance: Intrapartum Consensus Guideline.

OBJECTIVE: To present evidence and recommendations regarding use, classification, interpretation, response, and documentation of fetal surveillance in the intrapartum period and to provide information to help minimize the risk of birth asphyxia while maintaining the lowest possible rate of obstetrical intervention. INTENDED USERS: Members of intrapartum care teams, including but not limited to obstetricians, family physicians, midwives and nurses, and their learners TARGET POPULATION: Intrapartum women OPTIONS: All methods of uterine activity assessment and fetal heart rate surveillance were considered in developing this document. OUTCOMES: The impact, benefits, and risks of different methods of surveillance on the diverse maternal-fetal health conditions have been reviewed based on current evidence and expert opinion. No fetal surveillance method will provide 100% detection of fetal compromise; thus, all FHS methods are viewed as screening tests. As the evidence continues to evolve, caregivers from all disciplines are encouraged to attend evidence-based Canadian educational programs every 2 years. EVIDENCE: Literature published between January 1976 and February 2019 was reviewed. Medline, the Cochrane Database, and international guidelines were used to search the literature for all studies on intrapartum fetal surveillance. VALIDATION METHODS: The principal and contributing authors agreed to the content and recommendations. The Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The level of evidence has been determined using the criteria and classifications of the Canadian Task Force on Preventive Health Care. BENEFITS, HARM, AND COSTS: Consistent interdisciplinary use of the guideline, appropriate equipment, and trained professional staff enhances safe intrapartum care. Women and their support person(s) should be informed of the benefits and harms of different methods of fetal health surveillance. RECOMMENDATIONS: CommunicationSupport During Active LabourPrinciples of Intrapartum Fetal SurveillanceSelecting the Method of Fetal Heart Rate Monitoring: Intermittent Auscultation or Electronic Fetal MonitoringPaper SpeedAdmission AssessmentsEpidural AnalgesiaIntermittent Auscultation in LabourElectronic Fetal Monitoring in LabourClassification of Intrapartum Fetal SurveillanceMaternal Heart RateFetal Health Surveillance Assessment in the Active Second Stage of LabourIntrauterine ResuscitationDigital Fetal Scalp StimulationFetal Scalp Blood SamplingUmbilical Cord Blood GasesDocumentationFetal Surveillance Technology Not RecommendedFetal Health Surveillance Education.

No396 - Surveillance du bien-être fœtal : Directive clinique de consensus des soins intrapartum.

OBJECTIF: La présente directive fournit des données probantes et des recommandations relativement à la surveillance fœtale en période intrapartum par rapport à son utilisation, à sa classification, à son interprétation, aux réactions du fournisseur de soins et à l'inscription des données de surveillance. Cette directive vise à fournir les renseignements qui peuvent potentiellement limiter le risque d'asphyxie du nouveau-né tout en maintenant les interventions obstétricales au plus bas taux possible. UTILISATEURS CONCERNéS: Les membres de l'équipe de soins intrapartum, y compris, notamment, les obstétriciens, les médecins de famille, les sages-femmes, les infirmières et leurs apprenants. POPULATION CIBLE: Femmes en période intrapartum. OPTIONS: Toutes les méthodes d'évaluation de l'activité utérine et de surveillance de la fréquence cardiaque fœtale ont été prises en compte dans l'élaboration du présent document. RéSULTATS: Les conséquences, bienfaits et risques des différentes méthodes de surveillance sur la variété d'états de santé fœto-maternelle ont fait l'objet d'évaluations fondées sur les données probantes actuelles et l'opinion de spécialistes. Aucune méthode de surveillance fœtale n'offre une détection infaillible de tout danger pour le fœtus; ainsi, toutes les méthodes de SBEF sont considérées comme des tests de dépistage. Étant donné que les données probantes évoluent continuellement, les fournisseurs de soins, toutes disciplines confondues, sont encouragés à suivre tous les deux ans un programme de formation canadien fondé sur des données probantes. DONNéES PROBANTES: La littérature publiée entre juin 1976 et février 2019 a été passée en revue. Les bases de données Medline et Cochrane ainsi que les directives internationales ont été utilisées afin de chercher dans la littérature toutes les études sur la surveillance fœtale intrapartum. MéTHODES DE VALIDATION: Le contenu et les recommandations ont été approuvés par les auteurs principaux et collaborateurs. Le conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version définitive aux fins de publication. La qualité des résultats a été déterminée au moyen des critères et des catégories établis par le Groupe d'étude canadien sur les soins de santé préventifs. AVANTAGES, PRéJUDICE ET COûTS: L'utilisation interdisciplinaire cohérente de la présente directive, l'équipement adéquat et le personnel compétent améliorent la sécurité des soins intrapartum. Il convient d'informer les femmes et leurs personnes de soutien des bienfaits et des préjudices inhérents aux différentes méthodes de surveillance du bien-être fœtal. RECOMMANDATIONS: Communication Soutien durant la phase active du travail Principes de surveillance fœtale intrapartum Choix de la méthode de surveillance de la fréquence cardiaque fœtale : auscultation intermittente ou surveillance électronique fœtale Vitesse de déroulement du papier Évaluation d'admission Anesthésie péridurale Auscultation intermittente pendant le travail Surveillance électronique fœtale pendant le travail Classification de la surveillance fœtale intrapartum Fréquence cardiaque maternelle Évaluation de la surveillance du bien-être fœtal à la phase active du deuxième stade du travail Réanimation intra-utérine Stimulation digitale du cuir chevelu fœtal Prélèvement de sang au cuir chevelu fœtal Gazométries du cordon ombilical Données à consigner Technologies de surveillance fœtale non recommandées à l'heure actuelle Formation en surveillance du bien-être fœtal.

No. 282-Rural Maternity Care.

OBJECTIVE: To provide an overview of current information on issues in maternity care relevant to rural populations . EVIDENCE: Medline was searched for articles published in English from 1995 to 2012 about rural maternity care . Relevant publications and position papers from appropriate organizations were also reviewed . OUTCOMES: This information will help obstetrical care providers in rural areas to continue providing quality care for women in their communities .

Complex Chromosomal Rearrangements in B-Cell Lymphoma: Evidence of Chromoanagenesis? A Case Report.

Genomic instability is a well-known hallmark of cancer. Recent genome sequencing studies have led to the identification of novel phenomena called chromothripsis and chromoanasynthesis in which complex genomic rearrangements are thought to be derived from a single catastrophic event rather than by several incremental steps. A new term chromoanagenesis or chromosomal rebirth was coined recently to group these two one-step catastrophic events together. These phenomena suggest an evolutionary modality for cancer cells to circumvent individual mutational events with one simultaneous shattering of chromosomes resulting in the random reassembling of segmented genetic material to form complex derivative chromosomes. We report a case of possible chromoanagenesis in a patient with diffuse large B-cell lymphoma. Chromosome analysis from the biopsy showed a complex karyotype with multiple numerical and structural rearrangements including a translocation of chromosomes 3 and 7 involving the BCL6 gene region, with the derivative chromosome further rearranging with chromosomes 14, 7, and 22 with involvement of the IGH gene region. Fluorescence in situ hybridization studies confirmed these findings. Chromosomal microarray studies showed multiple complex copy number variations including a chromosome 12 abnormality, the complexity of which appears to suggest the phenomenon of chromoanagenesis. Our case further illustrates that lymphomagenesis can be complex and may arise from a catastrophic event resulting in multiple complex chromosome rearrangements.

Optimal strategy for obtaining routine chromosome analysis by using negative fractions of CD138 enriched plasma cells.

Fluorescence in situ hybridization (FISH) is superior to routine chromosome analysis (RCA) in detecting important prognostic genetic abnormalities in plasma cell dyscrasia (PCD); however, its sensitivity is hampered due to paucity of plasma cells (PC) in whole bone marrow (BM). Studies showed that the abnormality detection rate in enriched plasma cells (EPC) is greater than unselected plasma cells (UPC), but purification techniques are limiting to only FISH when sample volumes are inadequate. Not performing RCA may compromise patient care since RCA is equally important for detecting non-PC related abnormalities when the diagnosis is undefined. To resolve this critical issue, we designed a study where an immuno-magnetic CD138 enriched positive selection was used for FISH while the negative fraction (NF) was used to retrieve other myeloid elements for RCA. Parallel FISH studies were performed using UPC and CD138 EPC, while karyotyping was achieved using whole BM and discarded myeloid elements from the NF. Results showed that the abnormality rate of EPC was doubled compared to UPC for FISH, and CA displayed 100% success rate using the NF. PCD related chromosome abnormalities were confined to whole BM while non-PCD related abnormalities were found in both whole BM and NF. Our results demonstrate the feasibility of using the NF for RCA.

Rural maternity care.

OBJECTIVE: To provide an overview of current information on issues in maternity care relevant to rural populations. EVIDENCE: Medline was searched for articles published in English from 1995 to 2012 about rural maternity care. Relevant publications and position papers from appropriate organizations were also reviewed. OUTCOMES: This information will help obstetrical care providers in rural areas to continue providing quality care for women in their communities. Recommendations 1. Women who reside in rural and remote communities in Canada should receive high-quality maternity care as close to home as possible. 2. The provision of rural maternity care must be collaborative, woman- and family-centred, culturally sensitive, and respectful. 3. Rural maternity care services should be supported through active policies aligned with these recommendations. 4. While local access to surgical and anaesthetic services is desirable, there is evidence that good outcomes can be sustained within an integrated perinatal care system without local access to operative delivery. There is evidence that the outcomes are better when women do not have to travel far from their communities. Access to an integrated perinatal care system should be provided for all women. 5. The social and emotional needs of rural women must be considered in service planning. Women who are required to leave their communities to give birth should be supported both financially and emotionally. 6. Innovative interprofessional models should be implemented as part of the solution for high-quality, collaborative, and integrated care for rural and remote women. 7. Registered nurses are essential to the provision of high-quality rural maternity care throughout pregnancy, birth, and the postpartum period. Maternity nursing skills should be recognized as a fundamental part of generalist rural nursing skills. 8. Remuneration for maternity care providers should reflect the unique challenges and increased professional responsibility faced by providers in rural settings. Remuneration models should facilitate interprofessional collaboration. 9. Practitioners skilled in neonatal resuscitation and newborn care are essential to rural maternity care. 10. Training of rural maternity health care providers should include collaborative practice as well as the necessary clinical skills and competencies. Sites must be developed and supported to train midwives, nurses, and physicians and provide them with the skills necessary for rural maternity care. Training in rural and northern settings must be supported. 11. Generalist skills in maternity care, surgery, and anaesthesia are valued and should be supported in training programs in family medicine, surgery, and anaesthesia as well as nursing and midwifery. 12. All physicians and nurses should be exposed to maternity care in their training, and basic competencies should be met. 13. Quality improvement and outcome monitoring should be integral to all maternity care systems. 14. Support must be provided for ongoing, collaborative, interprofessional, and locally provided continuing education and patient safety programs.