Glycemic Control and Plasma Levels of Pro-Inflammatory and Pro-Thrombotic Biomarkers in Diabetic Patients Presenting with Acute Pulmonary Embolism.

Type I and type II diabetes are closely associated with a pro-inflammatory state and to a pro-thrombotic state. The role of glycemic control in pulmonary embolism (PE) is poorly understood and requires additional investigation. The aim of this study is to investigate the relationship between glycemic control and thrombo-inflammatory biomarkers in a PE patient cohort compared to normal samples. Demographic and clinical information for 86 diabetic patients and 106 non-diabetic patients presenting with acute PE was collected via retrospective chart review. Plasma levels of pro-inflammatory (C-reactive protein [CRP], tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]) and pro-thrombotic (d-dimer, plasminogen activator inhibitor-1 [PAI-1], tissue plasminogen activator [tPA], thrombin activatable fibrinolysis inhibitor [TAFI], von-Willebrand factor [vWF], endogenous glycosaminoglycans [GAGs]) biomarkers were drawn within 24 hours of diagnosis of acute PE. Data was also obtained for a population of healthy adult controls. All the pro-inflammatory and pro-thrombotic biomarkers were elevated in diabetic PE patients in comparison to healthy controls. None of the biomarkers were elevated in diabetic PE patients when compared to non-diabetic PE patients. There was no difference in the levels of the pro-inflammatory biomarkers according to glycemic control. The plasma level of TAFI was elevated in diabetic patients with poor glycemic control. Diabetic patients were more likely to have a more severe PE. These studies demonstrate that thrombo-inflammatory biomarkers are elevated in diabetic PE patients with associated comorbidities in comparison to normal individuals. However, there is no difference between the PE cohort alone in comparison to PE with diabetes. The role of TAFI within the continuum of diabetic vascular disease warrants additional investigation.

Endogenous Glycosaminoglycans in Various Pathologic Plasma Samples as Measured by a Fluorescent Quenching Method.

Endogenous glycosaminoglycans (GAGs) with a similar structure to heparin are widely distributed in various tissues. A fluorescence probe, namely Heparin Red, can detect polyanionic GAGs in plasma samples. The purpose of this study is to measure endogenous GAGs in various plasma samples obtained from different pathologic states in comparison to healthy controls utilizing this method. Plasma samples were obtained from patient groups including atrial fibrillation (AF), end-stage-renal-disease (ESRD), diabetes mellitus (DM), sepsis, cancer, liver disease (LD), and pulmonary embolism (PE). Normal human plasma (NHP) was used as healthy controls. The Heparin Red kit from Red Probes (Münster, Germany) was used for the quantification of endogenous GAGs in each sample before and after heparinase I degradation. All results were compiled as group means ± SD for comparison. NHP was found to have relatively low levels of endogenous GAGs with a mean concentration of 0.06 µg/mL. The AF, ESRD, DM, and sepsis patient samples had a mean endogenous GAG concentration of 0.55, 0.72, 0.92, and 0.94 µg/mL, respectively. The levels of endogenous GAGs were highest in cancer, LD, and PE patient plasma samples with a mean concentration of 1.95, 2.78, and 2.83 µg/mL, respectively. Heparinase I degradation resulted in a decline in GAG levels in plasma samples. These results clearly show that detectable Heparin Red sensitive endogenous GAGs are present in circulating plasma at varying levels in various patient groups. Additional studies are necessary to understand this complex pathophysiology.

The Relationship Between Thrombo-Inflammatory Biomarkers and Cellular Indices of Inflammation in Lymphoma Patients.

INTRODUCTION: Thrombo-inflammatory biomarkers play an important role in the pathogenesis of lymphoma. We aimed to characterize the interrelationship of thrombo-inflammatory biomarkers and blood cellular indices in lymphoma patients. MATERIALS AND METHODS: Ninety-eight lymphoma patient samples were collected from Lymphoma Center of Clinic of Hematology, University of Belgrade, Serbia. Normal controls (n = 50) represented plasma from healthy individuals. Plasminogen activator inhibitor (PAI-1), D-Dimer, factor XIII, C-reactive protein (CRP), microparticles (Mp), Von Willebrand factor (vWF), total protein S, urokinase-type plasminogen activator (uPA), tumor necrosis factor (TNFα), ß2-glycoprotein I (ß2GPI), and fibronectin levels were measured utilizing commercially-available ELISA methods. Thrombin generation profile (TGA) was measured using a fluorometric kinetic assay. Platelets, leukocytes, lymphocytes, and neutrophils were measured in conjunction with the complete blood profile. RESULTS: Statistically significant differences were noted in levels of PAI-1, D-Dimer, factor XIII, CRP, microparticles, vWF, uPA, TNFα, ß2GPI, fibronectin, and TGA when compared to normal (all P values < .001). Platelet to leukocyte ratio (PLA) correlated to TNFα and fibronectin (R = -0.31 and -0.53, respectively) and the platelet to neutrophil ratio (PNR) correlated to factor XIII and ß2GPI (R = 0.40 and 0.40, respectively). CONCLUSION: Plasma samples from lymphoma patients demonstrated a significantly altered thrombo-inflammatory biomarker profile that has notable correlations to blood cellular indices.

The COVID-19 Pandemic and the Need for an Integrated and Equitable Approach: An International Expert Consensus Paper.

BACKGROUND: One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. MANAGEMENT: Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. CURRENT ISSUES: The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. PERSPECTIVES: There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). CONCLUSION: The "PDA strategy" integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.

Outcomes of Chronic Myeloid Leukemia Patients With Early Molecular Response at 3 and 6 Months: A Comparative Analysis of Generic Imatinib and Glivec.

BACKGROUND: The molecular response at 3 months of the original imatinib (OI) in patients with chronic myeloid leukemia has prognostic significance; however, this has never been tested for generic imatinib (GI). PATIENTS AND METHODS: We evaluated the BCR-ABL1 [international reporting scale (IS)] transcript levels at 3 and 6 months to determine whether an early molecular response (EMR) had a prognostic effect on the outcome among chronic myeloid leukemia patients receiving GI. Ninety patients were divided into 2 groups, according to the imatinib they received, as OI (group A) and GI (group B). RESULTS: Two groups were equally balanced for age, gender, Sokal risk score, and optimal response. The 2 groups did not differ in achieving an EMR at 3 months, and patients with EMR at 3 months had significantly superior complete cytogenetic response and major molecular response rates compared with patients who did not achieve an EMR in both groups. The percentage of an optimal response [BCR-ABL1 (IS), < 1%] and a warning response [BCR-ABL1 (IS), 1%-10%] at 6 months was 93% and 95% for groups A and B, respectively (P = .553). Patients with an optimal response (OR) at both 3 and 6 months had significantly superior event-free survival rates compared with patients without an OR in groups A and B. CONCLUSION: The results of the present study have demonstrated most probably for the first time that an OR at 3 and 6 months in patients receiving either first-line GI and OI is clearly associated with greater response and event-free survival rates. Prospective randomized trials with larger numbers of patients and longer follow-up periods are needed to address the effect of EMR in patients receiving GI.

Allogeneic stem cell transplantation in a blast-phase chronic myeloid leukemia patient with carbapenem-resistant Klebsiella pneumoniae tricuspid valve endocarditis: A case report.

In chronic myeloid leukemia (CML), the occurrence of blastic transformation is rare. Treatment outcome is generally poor. Allogeneic stem cell transplantation (allo-SCT) is the only potentially curative treatment option for advanced-phase CML. Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates are associated with high morbidity and mortality rates, particularly in patients with haematological malignancies. Infection and colonization by these multiresistant bacteria may represent a challenge in SCT recipients for the management of post-transplantation complications, as well as for the eligibility to receive a transplant in patients who acquire the pathogen prior to the procedure. We herein report the case of a blast-phase CML patient with a highly resistant, CRKP-associated tricuspid valve endocarditis, who was treated with a combination of systemic antimicrobial therapy and surgical valve repair, and subsequently underwent a successful allo-SCT.

Complete Remission of Burkitt Lymphoma After Surgical Excision: A Case Report.

Burkitt lymphoma (BL) is a highly aggressive B cell non-Hodgkin lymphoma that has a high proliferation rate. The prognosis for BL is generally favorable, with cure rate of 75-90 % with modern chemoimmunotherapy regimens. Prompt administration of multiagent immunochemotherapy regimens is critical, because BL is almost always fatal if left untreated. Nevertheless here we report a case of BL that is still in complete remission after more than 4 years without any further treatment after surgical excision of the involved lymph node.

Isolated extramedullary cutaneous relapse despite concomitant severe graft-vs.-host disease and tissue chimerism analysis in a patient with acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: A case report.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with acute lymphoblastic leukemia (ALL). The curative potential of allo-HSCT for ALL is, in part, due to the graft-vs.-leukemia (GVL) effect, in addition to the intensive conditioning chemo-radiotherapy. However, relapse remains the major cause of treatment failure following allo-HSCT for ALL. In the allo-HSCT setting, testing for genetic markers of hematopoietic chimerism has become a part of the routine diagnostic program. Routine chimerism analysis is usually performed in peripheral blood or bone marrow; in fact, little is known about the value of tissue chimerism in patients with extramedullary relapse (EMR) after the allo-HSCT setting. The present study reports on, a case of a patient with ALL who experienced isolated cutaneous EMR despite ongoing graft-vs.-host disease (GVHD), and the results of peripheral blood and skin tissue chimerism studies using multiplex polymerase chain reaction (PCR) of short tandem repeats (STR-PCR). The present case demonstrates that, although complete remission and/or chimerism may be achieved in the bone marrow, chimerism achieved at the tissue level, and the subsequent GVL effect, may be limited, despite concomitant severe GVHD following allo-HSCT. Our tissue chimerism analysis results provide a good example of how skin tissue may be a 'sanctuary' site for effector cells of GVL, despite active GVHD and complete hematopoetic chimerism.

Myelodysplastic syndrome with t(9;22)(p24;q11.2), a BCR-JAK2 fusion: case report and review of the literature.

The human JAK2 gene is mainly targeted by two types of genetic lesions that play roles in the pathogenesis of hematologic malignancies: intragenic mutations and chromosomal translocations. Chromosomal translocations of JAK2 are typically associated with myeloid or lymphoid malignancies with an aggressive course and poor outcome. Here we report a t(9;22)(p24;q11.2) translocation, in a MDS patient and review results associated with BCR-JAK2 fusion reported in the literature.