This study aimed to explore the effectiveness and safety of Myxoma virus (MYXV) in MM cell lines and primary myeloma cells obtained from patients with multiple myeloma. Myeloma cells were isolated from MM patients and cultured. MYXV, lenalidomide, and bortezomib were used in MM cells. The cytotoxicity assay was investigated using WST-1. Apoptosis was assessed through flow cytometry with Annexin V/PI staining and caspase-9 concentrations using ELISA. To explore MYXV entry into MM cells, monoclonal antibodies were used. Moreover, to explore the mechanisms of MYXV entry into MM cells, we examined the level of GFP-labeled MYXV within the cells after blocking with monoclonal antibodies targeting BCMA, CD20, CD28, CD33, CD38, CD56, CD86, CD117, CD138, CD200, and CD307 in MM cells. The study demonstrated the effects of treating Myxoma virus with lenalidomide and bortezomib. The treatment resulted in reduced cell viability and increased caspase-9 expression. Only low-dose CD86 blockade showed a significant difference in MYXV entry into MM cells. The virus caused an increase in the rate of apoptosis in the cells, regardless of whether it was administered alone or in combination with drugs. The groups with the presence of the virus showed higher rates of early apoptosis. The Virus, Virus + Bortezomib, and Virus + Lenalidomide groups had significantly higher rates of early apoptosis (p < 0.001). However, the measurements of late apoptosis and necrosis showed variability. The addition of MYXV resulted in a statistically significant increase in early apoptosis in both newly diagnosed and refractory MM patients. Our results highlight that patient-based therapy should also be considered for the effective management of MM.

Multiple myeloma (MM), which affects plasma cells, is the second most common hematological malignancy. Despite the development of new drugs and treatment protocols, patient survival has not reached the desired level. In this study, we investigated the effects of Myxoma virus (MYXV), an oncolytic virus, on autophagy in myeloma cells. We analyzed protein expression of ATG-5, p62, Beclin-1, LC3B, and the apoptosis marker Bcl-2 as autophagy markers in human U-266 and mouse MOPC 315 myeloma cell lines treated with different doses of MYXV. In addition, autophagic images in myeloma cells were investigated using transmission electron microscopy (TEM). In the first 24 hours, which is the early stage of autophagy, ATG-5 and Beclin-1 expression were increased in the U-266 and MOPC-315 cell lines in the groups that received 15 multiplicity of infection (moi) MYXV. At 48 hours, a significant increase was detected in the expression of LC3B, which is a late indicator. Autophagosomes were observed in myeloma cells on TEM. MYXV shows an antimyeloma effect by increasing autophagy in myeloma cells.

Aims: This study aimed to explore the incidence of osteoporosis in patients with diabetes mellitus (DM) who have been on a long-term pioglitazone regimen, and to ascertain the link between pioglitazone usage and the onset of osteoporosis. Methods: We enrolled patients prospectively and conducted a comparative analysis between two groups of DM patients: those who had been using pioglitazone for a period exceeding two years, and those with no history of pioglitazone use. Bone Mineral Density (BMD) was assessed using dual energy X-ray absorptiometry (DEXA). Results: There were no significant differences in age, gender, disease duration, fasting plasma glucose levels, and HbA1c levels between pioglitazone users and non-users. However, a significant variation was found in the BMD measurements. Patients on pioglitazone had an L1-L4 vertebra BMD T-score of -1.3, compared to -0.9 in non-users (p<0.05), signifying a substantial divergence in BMD between both cohorts. Furthermore, it was observed that patients with a disease duration of less than 10 years had higher BMD T-scores compared to those with disease durations exceeding 10 years, suggesting a decrease in BMD with increased disease longevity. Moreover, a higher BMD was observed in patients aged less than 50 years in comparison to those aged over 60 years. Conclusion: Despite the clinical preference for pioglitazone in the management of DM and insulin resistance, our findings suggest that it may affect bone metabolism adversely in the long run. Hence, careful monitoring is advised during extended periods of pioglitazone use. To investigate the incidence of osteoporosis in patients with DM who use pioglitazone for a long time and to determine the relationship between pioglitazone and the cause of this osteoporosis.

Aims: MM (Multiple myeloma) is the second most common hematological malignancy. In addition to the recent advances in treatment, new parameters are used in clinical practice in diagnosis and follow-up. sFLC (free chain kappa and lambda) shows the activation of the disease depending on the rate of MM malignant cell secretion in serum. However, the plasma cell (PC) ratio in bone marrow biopsy is still the gold standard in diagnosis. We examined the dynamic correlation between the PC ratio and the number of sFLC-related cells and the secretion rate. We aimed to examine whether a low PC ratio could be in a more aggressive form with a higher sFLC secretion with too much activity, thus examining the correlation between them. Methods: A total of 62 newly diagnosed MM patients admitted to Başkent University Faculty of Medicine İstanbul Hospital were included in the study. At the time of diagnosis, sFLC values were requested simultaneously with bone marrow biopsy. Radiological images were obtained with PET CT/MRI or CT. Results: In all MM groups, bone marrow PH percentages were not correlated with sFLC regardless of subtype. IgG kappa type MM had the highest sFLC values despite the lowest number of PHs, while Lambda light chain MM had the lowest sFLC despite the highest PH rates. Conclusion: These results showed us that sFLC rates are independent of the percentage of PC in MM. We believe that the two are not correlated and should be followed up together in the follow-up of the disease.

Background: We have aimed at exposing left ventricular diastolic functions and the presence of known genetic mutations for familial erythrocytosis, in patients who exhibit idiopathic erythrocytosis. Methods: Sixty-four patients with idiopathic erythrocytosis (mean age, 46.4 ± 2.7 years) and 30 age-matched healthy subjects were prospectively evaluated. The regions of interest of the erythropoietin receptor, hemoglobin beta-globin, von Hippel-Lindau, hypoxia-inducible factor 2 alpha, and Egl-9 family hypoxia-inducible factor genes were amplified by PCR. Left ventricular (LV) mass was measured by M-mode and 2-dimensional echocardiography. LV diastolic functions were assessed by conventional echocardiography and tissue Doppler imaging. Results: As a result of genetic analyses, genetic mutations for familial erythrocytosis were detected in 5 patients. It has been observed in our study that the risk of cardiovascular disorders is higher in patients. Interventricular septum thickness, left atrial diameter, and some diastolic function parameters such as deceleration time and isovolumetric relaxation time have been found to be significantly higher in idiopathic erythrocytosis group than in the controls. Conclusion: This study has shown that LV diastolic functions were impaired in patients with idiopathic erythrocytosis. In this patient group with increased risk of cardiovascular disorders, the frequent genetic mutations have been detected in 5 patients only. Therefore, further clinical investigations are needed as novel genetic mutations may be discovered in patients with idiopathic erythrocytosis because of cardiovascular risk.

Rationale: Portal vein thrombosis (PVT) has a complex pathophysiologic pathway and may cause life-threatening clinical complications. Malignancies, hepatic cirrhosis, auto-immune disorders, previous splenectomy, and other causes of thrombocytosis (over 1,000,000/mL) are the most common causes of PVT. On the other hand, hematologic disorders and infectious processes in the abdominal cavity may cause PVT uncommonly. We present a case of PVT following acute appendicitis and laparoscopic appendectomy in this report. Patient concerns: A 32-year-old male was admitted to our emergency room due to lower quadrant pain and vomiting. Acute appendicitis was diagnosed and after a routine laparoscopic appendectomy, the patient was discharged. The patient was admitted to the emergency room with nonspecific epigastric pain on postoperative day 30. Diagnoses: Portal vein thrombosis was diagnosed by computed tomography. Hematologic investigations revealed a homozygous mutation of the methylene tetrahydrofolate 1298 gene. Interventions: Immediate low-molecular-weight heparin administration was initiated. The gastrointestinal system council and interventional radiology team opted for a medical approach and converted the low-molecular-weight heparin to apixaban. Outcomes: The computed tomography revealed the complete resolution of the thrombus on postoperative day 100. Lessons: Laparoscopic appendectomy can be complicated by portomesenteric axis thrombosis. When unusual findings are encountered during the postoperative follow-up period, rapid and detailed examinations should be performed.