Signet ring cell carcinoma metastasis in the bone marrow accompanied by cancer related thrombotic microangiopathy as a first presentation.

Cancer related thrombotic microangiopathies usually cause a diagnostic dilemma for hematologists and clinicians. In this case report, we presented a fifty-nine-year-old man who was admitted to our hospital with microangiopathic hemolytic anemia and thrombocytopenia due to the carcinoma metastasis to the bone marrow. As a result of rapid evaluations, it was revealed that the histological subtype of the cancer was signet ring cell carcinoma, and despite all the interventions, the patient died at a very short time after the initial presentation. Regardless of all the innovations in the diagnosis and treatment of thrombotic microangiopathies, cancer-associated thrombotic microangiopathy is still fatal and deadly today.

The Utility of CONUT Score in Diffuse Large B Cell Lymphoma Patients.

BACKGROUND: Assessment of nutritional status is gaining more importance in cancer patients because nutritional status is associated with response to chemotherapy, side effects of cancer treatment and disease progression. Several studies that were performed on patients with solid malignancies have shown the clinical significance of CONUT score (Controlling nutritional status). AIMS: Therefore we tried to show the utility of CONUT score in newly diagnosed Diffuse Large B Cell Lymphoma (DLBCL) patients which is the most frequently seen B Cell Lymphoma type. METHODS: Data of the 81 patients diagnosed with DLBCL were retrospectively evaluated. The primary endpoint of our study was to evaluate and classify newly diagnosed DLBCL patients according to the CONUT score and secondary endpoint was to show any relationship with CONUT score and overall survival. Patients' demographics, treatment details, stages, extranodal involvements, the presence of bulky disease, response to treatment options and overall survivals were evaluated from medical recordings. RESULTS: Univariate cox regression analysis CONUT score was associated with overall survival (HR: 2.34-95% CI: 1.55-3.24 P = 0.040). On multivariate Cox regression analysis model CONUT score ≥5 was found to be an independent prognostic factor for overall survival (HR: 4.96-95% CI: 1.77-13.97- P = 0.002). CONCLUSION: The value of obtaining nutritional status in cancer patients is underestimated and CONUT score is simple, easily applicable and in our opinion is going to fill the gap especially in DLBCL patients.

Reproductive toxic effects and possible mechanisms of zonisamide in male rats.

Zonisamide (ZNS) is an anticonvulsant which is used to treat the symptoms of epilepsy. Although it is frequently used during reproductive ages, studies that investigated the effects of ZNS on reproductive system are limited. Therefore, we aimed to assess the effects of ZNS on male reproductive system by oral administration to rats in 25, 50, and 100 mg/kg doses for 28 days. After the exposure period, sperm concentration, motility, morphology, and DNA damage, as biomarkers of reproductive toxic effects, were determined, and histopathological examination of testis was performed. In addition, levels of the hormones that play a role in the regulation of reproductive functions, such as follicle-stimulating hormone, luteinizing hormone (LH), and testosterone were measured and the levels of oxidative stress biomarkers that take part in the reproductive pathologies such as catalase, superoxide dismutase, glutathione, and malondialdehyde, were determined. Reproductive toxic effects related to ZNS administration were shown by the significant decrease of sperm concentration and normal sperm morphology in ZNS groups. Additionally, pathological findings were observed in the testicular tissues of ZNS-administered groups dose dependently. In addition, serum LH and testosterone levels were significantly decreased in the ZNS groups. Decreased catalase activities and increased malondialdehyde levels in ZNS groups were evaluated as oxidative stress findings in the testis tissue. It could be expressed that ZNS administration induced dose-dependent reproductive toxic effects in rats, and pathological findings associated with the reproductive system could be the result of that hormonal changes and testicular oxidative stress, which in turn might be considered as possible mechanisms of male reproductive toxicity.

Assessment of trazodone-induced cardiotoxicity after repeated doses in rats.

Trazodone (TRZ) is an antidepressant drug commonly used in the treatment of depression, anxiety, and insomnia. Although some studies demonstrated the adverse effects of TRZ related to cardiovascular system, the conflicting results were observed in these studies. Therefore, we aimed to investigate the cardiac adverse effects of TRZ in rats at repeated doses in our study. In accordance with this purpose, TRZ was administered orally to rats at 5, 10, and 20 mg/kg doses for 28 days. Electrocardiogram records, serum aspartate aminotransferase (AST), lactate dehydrogenase, creatine kinase-myoglobin band, cardiac troponin-T (cTn-T) levels, DNA damage in cardiomyocytes, and histologic view of heart tissues were evaluated. In addition, glutathione (GSH) and malondialdehyde (MDA) levels were measured to determine the oxidative status of cardiac tissue after TRZ administration. Heart rate was decreased, PR interval was prolonged, and QRS and T amplitudes were decreased in 20 mg/kg TRZ-administered group compared to the control group. Serum AST and cTn-T levels were significantly increased in 10 and 20 mg/kg TRZ-administered rats with respect to control rats. DNA damage was significantly increased in these groups. Additionally, degenerative histopathologic findings were observed in TRZ-administered groups. Although there was no difference in MDA levels between groups, GSH levels were significantly decreased in 10 and 20 mg/kg TRZ-administered groups compared to the control group. Our results have shown that TRZ induced cardiotoxicity in rats dose-dependently. It is assumed that oxidative stress related to GSH depletion may be accompanied by these adverse effects.

Frailty in patients with acute myeloid leukaemia, conceptual misapprehension of chronological age.

In haematology practice, patients with acute myeloid leukaemia (AML) are generally assessed for frailty only if they are older and not able to tolerate intensive and remission targeted treatments. We aimed to focus on frailty in patients with AML, in all ages and aimed to evaluate its role and practicality in daily routine. Data of patients diagnosed and treated for AML between 2006 and 2016 are recorded and assessed for their survival predictivity. One hundred and ninety-seven patients were <65 years of age and 175 were ≥65. Majority of the younger patients showed ECOG 2 performance (119, 60.4%). Combined with ECOG scale, G8 scale showed survival predictivity in younger patients as well as older patients. Nutritional status showed a strong predictivity in younger patients while remained insignificant in older patients. VES13 scale showed similar predictivity strength for survival in both age groups (p = .001). Young AML patients should be thoroughly evaluated as older patients. ECOG performance evaluation should be supported with further scales. Young patients with lower ECOG scores may be regarded as vulnerable with scales embracing dimensions such as nutrition, perception of disease, depression and cognition. Nutrition should be within the main goals of intensive treatment and is related with survival.

CD11c expression in chronic lymphocytic leukemia revisited, related with complications and survival.

INTRODUCTION: Chronic lymphocytic leukemia (CLL) is a disorder of mature but dysfunctional monoclonal B cells. Microenvironment, antigenic stimulation and genetical mutations are demonstrated in etiopathogenesis. We aimed to evaluate the expression of CD11c in patients with CLL and its possible clinical significance. METHODS: Data of 259 patients with CLL between 2010 and 2016 in Trakya University Faculty of Medicine, including age at diagnosis, sex, whole blood count, stage, percentage of CLL cells in bone marrow, line of treatments, development of Richter's transformation and secondary tumors, autoimmune complications, IgG level, prognostic cytogenetic analysis, and length of survival were recorded from files. RESULTS: 151 patients were male (58.3%) and 108 were male (41.7%). Mean age was 70 (21-92) years. CD11c was observed to be positive (>%20) in 103 patients (39.8%). Development of Richter's transformation, secondary tumors and ITP was significantly frequent in patients with CD11c positivity (P values .000, .003, .000 respectively). Also, IgG levels were significantly lower in this group (P = .000). Hemoglobin level, RAI stage and bone marrow CLL infiltration percentage were statistically related with CD11c (P values .036, .037, .000 respectively). Finally, CD11c was statistically related (in positive group 70 months, negative group 79 months, P = .001). CONCLUSION: CD11c, expressed not only in Hairy cell leukemia but also in dendritic cells, macrophages and monocytes is a differentiation marker for inflammation. Prolonged inflammation in the microenvironment of CLL cells may cause a susceptibility to autoimmune disorders and secondary tumors in CLL, in this way, an increase in mortality.

Eculizumab therapy in a patient with dense-deposit disease associated with partial lipodystropy.

BACKGROUND: Dense deposit disease (DDD) (also known as membranoproliferative glomerulonephritis type II) in childhood is a rare glomerulonephritis with frequent progression to end-stage renal disease (ESRD) and a high recurrence after kidney transplantation. The pathophysiologic basis of DDD is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade. CASE-DIAGNOSIS/TREATMENT: A 14-year-old girl presented with edema and nephrotic range proteinuria. Blood tests showed hypoalbuminemia, nephrotic range proteinuria, normal renal function, and a low C3 level. Renal biopsy confirmed the diagnosis of crescentic DDD. Complement analysis revealed strong AP activation (low C3), positive C3 nephritic factor (C3NeF), and a decreased complement factor H (CFH) levels with CFH polymorphisms. Therapy with eculizumab was considered after the failure of corticosteroid and plasmapheresis to modulate the ongoing massive proteinuria and persistence of low serum C3 levels. There was a marked clinical and biochemical response following the administration of eculizumab. CONCLUSIONS: Our case emphasizes the efficacy of eculizumab in the management of crescentic DDD in a patient with a normal renal function, in a short follow-up period. Considering previously reported cases, it appears that eculizumab represents a promising new approach which may prevent progression to ESRD in a subset of patients with DDD.

In the search for new anticancer drugs. 28. Synthesis and evaluation of highly active aminoxyl labeled amino acid derivatives containing the [N'-(2-chloroethyl)-N'-nitrosoamino]carbonyl group.

The aminoxyl (nitroxyl) labeled (2-chloroethyl)nitrosocarbamoyl (CNC) derivatives of amino acids, i.e., N-[[N'-(2-chloroethyl)-N'-nitrosoamino]carbonyl]-A-(1-oxy-2,2,6,6- tetramethylpiperidin-4-yl)amides, A = glycyl (10a), A = L-alanyl (10b), A = L-valyl (10c), A = L-phenylalanyl (10d), were synthesized and evaluated in vitro for their anticancer activities against the murine lymphocytic leukemia P388. Compounds 10a-d possessed activities ranging from 242 to 456% increase in life span (%ILS). All CDF1 male mice treated with the highly active compounds 10b and 10c at 12 mg/kg/day for 9 days were alive after 30 days. Compounds 10a-d were then tested in vivo against the murine lymphoid leukemia L1210. Compounds 10a-d exhibited, on day 60, a %ILS of 496, 663, 663, and 581, respectively. All CDF1 male mice treated with the highly active compounds 10b and 10c at 12 mg/kg/day for 9 days were alive after 60 days. The lipophilicities of compounds 10a-d were determined using the UV method. The %ILS parameters obtained against the P388 and L1210 tumor lines were correlated with the corresponding lipophilicities, and a trend was generally observed toward an increase in cytotoxicity with a concomitant decrease in hydrophobicity.