Preclinical Studies on Convalescent Human Immune Plasma-Derived Exosome: Omics and Antiviral Properties to SARS-CoV-2.

The scale of the COVID-19 pandemic forced urgent measures for the development of new therapeutics. One of these strategies is the use of convalescent plasma (CP) as a conventional source for passive immunity. Recently, there has been interest in CP-derived exosomes. In this report, we present a structural, biochemical, and biological characterization of our proprietary product, convalescent human immune plasma-derived exosome (ChipEXO), following the guidelines set forth by the Turkish Ministry of Health and the Turkish Red Crescent, the Good Manufacturing Practice, the International Society for Extracellular Vesicles, and the Gene Ontology Consortium. The data support the safety and efficacy of this product against SARS-CoV-2 infections in preclinical models.

Thrombotic Thrombocytopenic Purpura Cases and Consumption of Large Quantities of Energy Drink: Related or Coincidence?

The vast majority of cases of thrombotic thrombocytopenic purpura (TTP) are the result of acquired antibodies which inhibit the activity of the ADAMTS13 enzyme. Acquired TTP is more frequently seen in young females or in individuals with autoimmune disease. The development of antibodies against ADAMTS13 may also result from the administration or consumption of drugs and other substances. However, specific laboratory tests to identify the pathogenic mechanism of a particular drug may not be available, and the role of a potentially implicated drug or other ingested substance may not be clear. In this report we present 2 acquired TTP cases involving the consumption of a large amount of energy drink.

Meeting Report: The Equality Project on Endocrine Complications in Thalassemia: Selected Highlights from the First Turkish Congress, Antalya, 10th-11th December 2018.

Major difficulties reported by endocrinologists /pediatricians/ hematologists in the care of thalassemic patients with endocrine complications were: lack of facilities, correct interpretation of tests, unfamiliarity with medical treatment and the cost of diagnostics and therapeutics. Therefore, there is a felt need to educate and train more endocrinologists/pediatricians/hematologists in this field in order to optimise growth and prevent endocrine complications. To achieve this goal, in 2015, a project called Equality was submitted by three countries (Turkey, Spain and Italy) and approved by the European Union (EU) with the aim to train doctors and nurses, taking care of youth and young adults TM patients, in the prevention, diagnosis, and management of endocrine disorders. The selected highlights of the First Turkish Congress held in Antalya (10th-11th December 2018) are reported. Overall the conference provided a wide coverage of conventional treatment of thalassemias and endocrine complications in patients with ß-thalassemia major. Regular surveillance, early diagnosis, treatment and follow-up in a multi-disciplinary specialized setting are recommended.

Combination therapy with azacitidine, etoposide, and cytarabine in the treatment of elderly acute myeloid leukemia patients: A single center experience.

AIMS: The prognosis of acute myeloid leukemia (AML) in elderly patients is worse due to age and comorbidities. Lately, monotherapy with hypomethylating agents like azacitidine (Aza) has been used to prolong overall survival (OS) in AML patients. Herein, we present a retrospective study investigating treatment responses and OS of Aza in combination with etoposide (Eto) and cytarabine (ARA-C) in elderly. MATERIALS AND METHODS: In this study, therapies and outcomes of 37 newly diagnosed AML patients, >60 years old, and ineligible for intensive chemotherapy were investigated retrospectively. Patients were grouped according to the treatments they received as follows - Group 1: low-dose conventional therapies as hydroxyurea, low-dose ARA-C, or best supportive care (n = 11); Group 2: Aza alone (n = 6); Group 3: Aza in combination with Eto and ARA-C (Aza + Eto + ARA-C, n = 20). RESULTS: It was found that an Aza + Eto + ARA-C combination therapy had significantly better overall response rates (P = 0.002). Combination group had significantly better OS than Group 1 (8 months vs. 1 month, P < 0.001), the difference between combination and monotherapy was not significant. The OS was also associated with age and performance status, but the difference was still statistically significant after adjustment for these factors, especially for patients with younger age and better performance. CONCLUSIONS: We concluded that combination therapy of Aza with Eto and ARA-C increases response rates, and prolong survival for this poor prognosed patient group. We believe that larger controlled studies investigating Aza combinations with other antileukemic drugs will contribute to the development of tolerable treatment protocols for elderly AML patients.

Heterozygote Hemoglobin G-Coushatta as the Cause of a Falsely Decreased Hemoglobin A1C in an Ion-exchange HPLC Method.

Glycated hemoglobin (HbA1c) is used for the assessment of glycemic control in patients with diabetes. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA1c measurement. Here, we report two cases of Hemoglobin G-Coushatta (HBB:c.68A>C) variant that interferes in the measurement of HbA1c by a cation-exchange HPLC (CE-HPLC) method. HbA1c was measured by a CE-HPLC method in a Tosoh HLC-723 G7 instrument. The HbA1c levels were 2.9% and 4%. These results alerted us to a possible presence of hemoglobinopathy. In the hemoglobin variant analysis, HbA2 levels were detected as 78.3% and 40.7% by HPLC using the short program for the Biorad Variant II. HbA1c levels were measured by an immunoturbidimetric assay in a Siemens Dimension instrument. HbA1c levels were reported as 5.5% and 5.3%. DNA mutation analysis was performed to detect the abnormal hemoglobin variant. Presence of Hemoglobin G-Coushatta variant was detected in the patients. The Hb G-Coushatta variants have an impact on the determination of glycated hemoglobin levels using CEHPLC resulting in a false low value. Therefore, it is necessary to use another measurement method.

The Predictive Role of the Neutrophil/Lymphocyte Ratio in Survival with Multiple Myeloma: A Single Center Experience.

BACKGROUND: Recent studies have shown a positive correlation between tumor-related immune response markers and the poor outcome in solid tumors. In this study, we aimed to investigate the neutrophil/lymphocyte ratio (NLR) in multiple myeloma. To the best of our knowledge, this would be the second report concerning this topic. METHODS: We retrospectively reviewed the data for 52 multiple myeloma patients. The patients were grouped using the baseline NLR as NLR ≤ 1.72 and NLR > 1.72 using receiver operating characteristic analysis to determine a cut off. We compared the two groups in terms of both the known prognostic factors of the myeloma and the overall survival (OS). RESULTS: Our study showed that NLR is associated with C-reactive protein and ß2 microglobulin (P = 0.02 and P = 0.001, respectively). The patients with NLR > 1.72 had significantly worse stages, performance status, and kidney functions. The whole group's OS was estimated as 35.1 months while the patients with lower NLR had better OS when compared with those with NLR > 1.72 (42.75 and 26.14 months, respectively, P: 0.04). CONCLUSION: Neutrophil/lymphocyte ratio, which is associated with stage, performance status, and kidney functions, can be used in daily practice as a predictor for survival in multiple myeloma. Simply adding NLR to the routine charts may enrich our data for larger studies.

Comparative Evaluation of Common Comorbidity Scores and Freiburger Comorbidity Index as Prognostic Variables in a Real Life Multiple Myeloma Population.

Multiple myeloma (MM) is a disease of the geriatric population with a median age at diagnosis of 69 years but most clinicians consider performance status and comorbidities rather than chronological age in determining prognosis and treatment. The purpose of this study was to assess whether and which comorbidity indices predict survival in a real life population of MM. We calculated Charlson Comorbidity Index (CCI), age combined Charlson index (CCI-age), Hematopoietic cell transplantation-specific comorbidity index (HCT-SCI) and Freiburger comorbidity index (FCI) retrospectively for 66 MM patients and compared their impact on treatment responses and overall survival (OS). Treatment response was significantly worse in groups with high CCI, CCI-age, HCT-SCI scales (p < 0.05), but FCI's effect on treatment response was not significant. However, while no significant relationship was determined between other comorbidity indices with OS, it was related only with FCI-CI (p = 0.006). FCI, developed in this patient group, was the only prognostic index with a significant effect on OS in the evaluation of comorbidities in MM patients with different scores, but its relationship to treatment responses was not significant contrary to other indices. While this small patient group gave us hope regarding the use of FCI in practice, multi-center studies are still required.

The value of isovolumic acceleration for the assessment of right ventricular function in acute pulmonary embolism.

AIM: The aim of this study was to assess the value of tricuspid annulus myocardial isovolumic acceleration (IVA) in the assessment of right ventricular function in patients with acute pulmonary embolism (PE). METHODS: Fifteen patients (mean age 60.6±11.3 years) with acute PE were enrolled and a control group was formed of 15 patients with a similar mean age (60.3±11.5). Patients who were diagnosed with acute PE by thoracic computed tomography angiography underwent transthoracic echocardiography at the time of diagnosis and at one month after diagnosis. RESULTS: In the control group IVA was 2.8±0.2 m/s(2), while in the acute PE group, it was 2.0±0.1 m/s(2) at the time of diagnosis and 2.9±0.1 m/s(2) at the end of the first month. When IVA values of acute PE patients at the end of the first month were compared with their initial values and those of the control group, they had normalized (control and acute PE p<0.0001; control and PE at one-month follow-up p=0.983). CONCLUSION: In our study, IVA was shown to be a reliable marker of right ventricular systolic function in patients with acute PE.

Serious skin reaction associated with imatinib in a patient with chronic myeloid leukemia.

Imatinib mesylate (STI 571) is one of the fundamental chemotherapeutic agents used in the treatment of the chronic, accelerated and blastic phases of chronic myelocytic leukemia (CML), gastrointestinal stromal tumors and Philadelphia chromosome-positive acute lymphoblastic leukemia. It selectively inhibits receptor tyrosine kinases. Its effects limit the use of this drug. We present a case with a serious skin reaction requiring the discontinuation of the drug and that developed in relation to imatinib therapy. Six months prior, a 61-year-old male patient presenting to the hematology polyclinic with complaints of weight loss and sweating was hospitalized due to high leukocyte value. As a result of the hemogram, biochemistry analyses, peripheral blood smear examination, bone marrow aspiration evaluation, cytogenetic examination using FISH and PCR that were performed, CML was diagnosed. Additionally, to exclude myelofibrosis, we examined a bone marrow biopsy. Imatinib mesylate was started at 400 mg/day orally. In the fourth month of treatment, the patient complained of itching and a skin rash. Although the drug dose was reduced (300 mg/day), his complaints gradually increased. The skin biopsy result was superficial perivascular dermatitis. Imatinib was discontinued, and the patient was started on corticosteroid. The lesions disappeared completely. A month later, the patient was restarted on imatinib mesylate. However, the lesions recurred more prominently. His itching increased. The patient was considered intolerant to imatinib mesylate, and a second-generation tyrosine kinase inhibitor, dasatinib 100 mg/day, was started orally. The follow-up and treatment continues for the patient, who has been taking dasatinib 100 mg/day for the last two months without any skin finding or complaints. Imatinib mesylate-induced skin reactions are associated with the pharmacologic effect of the drug rather than hypersensitivity to the drug. Skin reactions are frequently observed, and this side effect is dose dependent. However, the interesting aspect of our case was that despite dose reduction, skin findings gradually increased, and eventually the drug had to be discontinued.