Coexisting Cardiac and Hematologic Disorders.

Patients with concomitant cardiac and hematologic disorders presenting for noncardiac surgery are challenging. Anemic patients with cardiac disease should be approached in a methodical fashion. Transfusion triggers and target should be based on underlying symptomatology. The approach to anticoagulation management in patients with artificial heart valves, cardiac devices, or severe heart failure in the operative setting must encompass a complete understanding of the rationale of a patient\u27s therapy as well as calculate the risk of changing this regimen. This article focuses common disorders and discusses strategies to optimize care in patients with coexisting cardiac and hematologic disease

Systematic profiling of DNMT3A variants reveals protein instability mediated by the DCAF8 E3 ubiquitin ligase adaptor

Clonal hematopoiesis is a prevalent age-related condition associated with greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations is unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, finding that 74% were loss-of-function mutations. Half of these variants exhibited reduced protein stability and, as a class, correlated with greater clonal expansion and AML development. We investigated the mechanisms underlying the instability using a CRISPR screen and uncovered regulated destruction of DNMT3A mediated by the DCAF8 E3 ubiquitin ligase adaptor. We establish a new paradigm to classify novel variants that has prognostic and potential therapeutic significance for patients with hematologic disease

Eosinophilic dermatosis of hematologic malignancy: a case report

Eosinophilic dermatosis of hematologic malignancy (EDHM) is a dermatosis characterized by tissue eosinophilia that has been previously reported as insect bite-like reaction. It is a rare condition with a wide variety of clinical presentations ranging from papules, nodules, or blisters that simulate arthropod bites, to the formation of plaques of differing sizes. We report a case of eosinophilic dermatosis of hematologic malignancy in a patient with a hematoproliferative disorder

Gaucher Disease and Myelofibrosis: A Combined Disease or a Misdiagnosis?

Background: Gaucher disease (GD) and primary myelofibrosis (PMF) share similar clinical and laboratory features, such as cytopenia, hepatosplenomegaly, and marrow fibrosis, often resulting in a misdiagnosis. Case Report: We report here the case of a young woman with hepatosplenomegaly, leukopenia, and thrombocytopenia. Based on bone marrow (BM) findings and on liver biopsy showing extramedullary hematopoiesis, an initial diagnosis of PMF was formulated. The patient refused stem cell transplantation from an HLA-identical sibling. Low-dose melphalan was given, without any improvement. Two years later, a BM evaluation showed Gaucher cells. Low glucocerebrosidase and high chitotriosidase levels were indicative for GD. Molecular analysis revealed N370S/complex I mutations. Enzyme replacement therapy with imiglucerase was commenced, resulting in clinical and hematological improvements. Due to an unexpected and persistent organomegaly, PMF combined with GD were suspected. JAK2V617F, JAK2 exon 12, MPL, calreticulin, and exon 9 mutations were negative, and BM examination showed no marrow fibrosis. PMF was excluded. Twenty years after starting treatment, the peripheral cell count and liver size were normal, whereas splenomegaly persisted. Conclusion: In order to avoid a misdiagnosis, a diagnostic algorithm for patients with hepatosplenomegaly combined with cytopenia is suggested

Gab Adapter Proteins as Therapeutic Targets for Hematologic Disease

The Grb-2 associated binder (Gab) family of scaffolding/adaptor/docking proteins is a group of three molecules with significant roles in cytokine receptor signaling. Gabs possess structural motifs for phosphorylation-dependent receptor recruitment, Grb2 binding, and activation of downstream signaling pathways through p85 and SHP-2. In addition, Gabs participate in hematopoiesis and regulation of immune response which can be aberrantly activated in cancer and inflammation. The multifunctionality of Gab adapters might suggest that they would be too difficult to consider as candidates for “targeted” therapy. However, the one drug/one target approach is giving way to the concept of one drug/multiple target approach since few cancers are addicted to a single signaling molecule for survival and combination drug therapies can be problematic. In this paper, we cover recent findings on Gab multi-functionality, binding partners, and their role in hematological malignancy and examine the concept of Gab-targeted therapy

Nosocomial Infection Outbreak due to SARS-COV-2 in a Hospital Unit of Particularly Vulnerable Patients

[Abstract] Objectives: To report a COVID-19 outbreak among workers and inpatients at a medical ward for especially vulnerable patients. Methods: Descriptive study of a nosocomial COVID-19 outbreak registered in March-April 2020 at medical ward of onco-hematological patients in an Spanish hospital. Confirmed cases were hospitalized patients, healthcare and non-healthcare workers who tested positive by PCR on a nasopharyngeal swab. Results: Twenty-two COVID-19 cases (12 workers and 10 inpatients) were laboratory-confirmed. Initial cases were a healthcare provider and a visitor who tested positive. The median patients age was 73 years (range 62-88). The main reason of admission was haematological in 8 patients and oncologic in 2. All patients followed an immunosuppressive treatment, 5/10 with high-flow oxygen nebulizations. Five patients presented a moderate/serious evolution, and 5 patients died. The mean workers age was 42.1±10.9. One healthworker required Intensive Care Unit admission, and all of them recovered completely. Conclusions: In the hospital setting, close patients surveillance for SARS-CoV-2 is essential, especially in immunosuppressed patients. Replacing nebulizations or high-flow oxygen therapies, when other equivalent options were available, to reduce dispersion, and controlling ventilation ducts, together with hygiene measures and an active follow-up on inpatients, visitors and workers appear to be important in preventing nosocomial outbreaks

Mannose-binding lectin gene variants and infections in patients receiving autologous stem cell transplantation

BACKGROUND: Serious infections are common in patients undergoing autologous stem cell transplantation (ASCT) mainly because of the effects of immunosuppression. The innate immune system plays an important role in the defense against different infections. Mannose binding lectin (MBL) is a central molecule of the innate immune system. There are several promoter polymorphisms and structural variants of the MBL2 gene that encodes for this protein. These variants produce low levels of MBL and have been associated with an increased risk for infections. METHODS: Prospective cohort study. The incidence, severity of infections and mortality in 72 consecutive patients with hematologic diseases who underwent ASCT between February 2006 and June 2008 in a tertiary referral center were analyzed according to their MBL2 genotype. INNO-LiPA MBL2 was used for MBL2 gene amplification and genotyping. Relative risks (RR) (IC95%) as measure of association were calculated. Multivariate analysis was performed using logistic regression. RESULTS: A statistically significant higher number of fungal infections was found in patients with MBL2 variants causing low MBL levels (21.1%versus1.9%, p=0.016). In this MBL2 variant group infection was more frequently the cause of mortality than in the MBL2 wild-type group (p=0.05). Although not statistically significant, there was a higher incidence of major infections in the MBL2 variant group as well as a higher number of infections caused by gram-positive bacteria. CONCLUSIONS: Low-producer MBL2 genotypes were associated with an increased number of fungal infections in ASCT patients, which would suggest that MBL has a protective role against such infections. ASCT patients with MBL2 variant genotypes are more likely to die as a result of an infection