Sezgin Etgül

The Evaluation of Neutrophil-Lymphocyte Ratio in Alzheimer’s Disease

Background/Aim: There is growing consensus in the literature that inflammation plays a significant role in the pathophysiology of Alzheimer’s disease (AD). The blood neutrophil-lymphocyte ratio (NLR) is a new, inexpensive and easily applicable marker of inflammation. The aim of this study was to investigate the association between NLR, as an inflammatory biomarker, and AD. Methods: 241 AD patients and 175 patients with normal cognitive function were evaluated in this study. Results: The mean ± SD NLR of AD patients was significantly higher than that of patients with normal cognitive function (3.21 ± 1.35 vs. 2.07 ± 0.74, p < 0.001, respectively). Receiver operating characteristic curve analysis suggested that the optimum NLR cutoff point for AD was 2.48 with 69.29% sensitivity, 79.43% specificity, 82.30% positive predictive values and 65.30% negative predictive values. Logistic regression analysis showed that elevated NLR (OR: 4.774, 95% CI: 2.821–8.076, p < 0.001) was an independent variable for predicting AD. Conclusion: Elderly people with AD have higher NLR than healthy controls. Elevated NLR levels are usually considered as an inflammatory marker. The results of this study suggested that inflammation plays a role in the pathogenesis of AD.

Epidemiology and emerging resistance in bacterial bloodstream infections in patients with hematologic malignancies

Abstract Background: The objective of this study was determine the frequency of bloodstream infections (BSIs) and the causative bacteria and their resistance patterns in patients with hematological malignancies (HMs) in a large tertiary care university hospital in Turkey over a 5-year period. Methods: A total of 2098 patients with HMs with 3703 neutropenic episodes were included. Patients were classified as high-risk (n = 843) and low-risk (n = 1255) groups and evaluated for frequency of BSIs, causative bacteria, and their resistance patterns. Results: The frequency of BSIs was 14.5%. The frequency of gram-negative BSIs in high-risk and low-risk groups was 10.7% and 5.4% (p < 0.001), respectively. The frequency of gram-positive BSIs in high-risk and low-risk groups was 7.0% and 3.9% (p < 0.001), respectively. Gram-negative bacteria predominated (52.6%), with Escherichia coli (17.3%) and Klebsiella spp. (11.0%) as the most frequent organisms. Coagulase-negative staphylococci (10.4%) and Corynebacterium spp. (6.3%) were the most common gram-positive bacteria (35.8%). The rate of extended-spectrum beta-lactamase (ESBL) production was 45% for E. coli and 58% for Klebsiella spp. Quinolone resistance was 58% for E. coli and 11% for Klebsiella spp.. The overall frequency of ceftazidime resistance in Pseudomonas aeruginosa was 28%, and 87% of Acinetobacter spp. were multidrug-resistant. Of Staphylococcus aureus isolates, 24.8% were resistant to methicillin. Conclusion: The dominating causes of BSIs in patients with HMs in our hospital are resistant gram-negative bacteria, which has made empirical antimicrobial choice a highly challenging issue in this patient population.

Optimizing mobilization strategies in difficult-to-mobilize patients: The role of plerixafor

Peripheral blood stem cell collection is currently the most widely used source for hematopoietic autologous transplantation. Several factors such as advanced age, previous chemotherapy, disease and marrow infiltration at the time of mobilization influence the efficacy of CD34(+) progenitor cell mobilization. Despite the safety and efficiency of the standard mobilization protocols (G-CSF ± chemotherapy), there is still a significant amount of mobilization failure rate (10-40%), which necessitate novel agents for effective mobilization. Plerixafor, is a novel agent, has been recently approved for mobilization of hematopoietic stem cells (HSCs). The combination of Plerixafor with G-CSF provides the collection of large numbers of stem cells in fewer apheresis sessions and can salvage those who fail with standard mobilization regimens. The development and optimization of practical algorithms for the use Plerixafor is crucial to make hematopoietic stem cell mobilization more efficient in a cost-effective way. This review is aimed at summarizing how to identify poor mobilizers, and define rational use of Plerixafor for planning mobilization in hard-to-mobilize patients.

Management of De Novo CML and Imatinib-Induced Acute Rhabdomyolysis With the Second-Generation TKI, Dasatinib

The aim of this report is to describe a newly diagnosed chronic myeloid leukemia (CML) patient who had imatinib mesylate (IM)-induced rhabdomyolysis and tolerated the second-generation tyrosine kinase inhibitor (TKI) dasatinib that controlled CML disease progression without precipitating the already present muscle damage. A 42-year-old man was admitted to the local hospital with left lumbar region pain. He had polycystic kidney disease, and leukocytosis in the routine tests had been observed. The patient admitted to our hematology outpatient unit for the evaluation of leukocytosis. After the investigations, he had been diagnosed as de novo chronic phase CML. In June 2014, he had been given IM 400 mg once a day. He was not taking any other drug. Pain began in both lower extremities 15 days after the start of medication. The patient’s baseline creatinine level was 1.5 mg/dL before the admission. The laboratory tests were as follows: creatinine 1.4 mg/dL, serum calcium and phosphorus levels in normal range, and creatine kinase (CK) levels 1533 U/L. Therefore, the patient was diagnosed as having rhabdomyolysis. The urine was clear in appearance, yellow colored, with a pH of 5, density 1010, protein glucose bilirubin ketone nitrite negative, and urobilinogen normal, with a few erythrocytes and leukocytes. Other causes of rhabdomyolysis (trauma or direct injury, excessive muscle activity, hereditary muscle enzyme defects, drugs and toxins, muscle hypoxia, metabolic and endocrine disorders, infections, temperature alterations, myocardial infarction, and stroke) were ruled out, and rhabdomyolysis was considered to have been caused by IM. We performed the Naranjo algorithm, and the score was 9 points. Therefore, IM treatment was stopped and secondgeneration TKI (dasatinib) was given instead. We preferred dasatinib because there are trials that confirmed the efficiency of dasatinib in patients with imatinib intolerance. Nilotinib could have also been used; however, its molecular mimicry cast doubts that it might cause the same intolerance and/or adverse events in terms of rhabdomyolysis. Two weeks after IM withdrawal, the pain in the patient’s extremities decreased, and CK levels were 195 U/L. His real-time polymerase chain reaction (PCR) analysis revealed that the disease was controlled with dasatinib treatment, and CK levels remained in normal ranges (Figure 1). He is still on follow-up with dasatinib in our clinic, without any sign of rhabdomyolysis. CML is a slowly progressive clonal malignant disease characterized by myeloid neoplastic expansion with heterogeneous clinical manifestations. CML could be functionally cured by the TKI drugs. IM is the first TKI to be used widely for CML treatment. Diarrhea, edema, myalgia, and skin reactions are common side effects of IM. In one previous study, myalgia occurred in 39% versus 22% of newly diagnosed chronic-phase CML patients who were treated with imatinib and dasatinib, respectively. Rarely, IM-induced rhabdomyolysis cases have been reported. Myalgia is a common side effect of IM. However, rhabdomyolysis with CK elevations is quite rare. In such a patient with CML, IM should be discontinued, and second-generation TKIs (such as dasatinib) should be administered. Because rhabdomyolysis recurs with the reintroduction of IM, the patient should be followed up while under secondgeneration TKIs. Dasatinib treatment could be used as an alternative TKI, so that CML remains under control during the rhabdomyolysis phase, and dasatinib does not precipitate the muscle damage with imatinib already present. It would have been better if we had investigated the plasma levels of imatinib in our patient; however, we failed to perform the plasma analyses. The interrelationships between IM and CK elevations are not well known. Some researchers suggest that IM-induced electrolyte imbalance is the reason for CK elevations. However, although our patient had polycystic kidney disease and creatinine levels of 1.4 mg/dL, he had no electrolyte imbalance. Monitoring the CML disease and TKI drug off-target risks are vital in clinical practice. Expected hematological, cytogenetic, and molecular responses to those drugs during the monitoring of CML vary based on some parameters. These parameters are the disease phase, mutational status, resistance profile, molecular BCR-ABL dynamics, compliance, patient drug adherence, and drug adverse effects. If there is myalgia with muscle weakness after the initiation of IM, rhabdomyolysis should be considered. No reports of rhabdomyolysis occurred during the clinical trial conducted for imatinib approval; however, postmarketing surveillance has captured some case reports of rhabdomyolysis. We have compared such cases in Table 1. In these cases, CK; complete blood count, including differential and platelet count; blood urea nitrogen; creatinine; routine electrolytes, including potassium, calcium, 579425 AOPXXX10.1177/1060028015579425Annals of PharmacotherapyMalkan et al research-article2015

Rebound Thrombocytosis following Induction Chemotherapy is an Independent Predictor of a Good Prognosis in Acute Myeloid Leukemia Patients Attaining First Complete Remission.

There are very few data about the relationship between acute myeloid leukemia (AML) prognosis and bone marrow recovery kinetics following chemotherapy. In this study, we aimed to assess the prognostic importance and clinical associations of neutrophil and platelet recovery rates and rebound thrombocytosis (RT) or neutrophilia (RN) in the postchemotherapy period for newly diagnosed AML patients. De novo AML patients diagnosed between October 2002 and December 2013 were evaluated retrospectively. One hundred patients were suitable for inclusion. Cox regression analysis using need for reinduction chemotherapy as a stratification parameter revealed RT as the only parameter predictive of OS, with borderline statistical significance (p = 0.06, OR = 7; 95% CI 0.92-53), and it was the only parameter predictive of DFS (p = 0.024, OR = 10; 95% CI 1.3-75). In order to understand whether RT or RN was related to a better marrow capacity or late consolidation, we considered neutrophil recovery time and platelet recovery time and nadir-first consolidation durations in all patients in the cohort. Both the marrow recovery duration and the time between marrow aplasia and first consolidation were shorter in RT and RN patients. To our knowledge, this is the first study to report a correlation between RT/RN and prognosis in AML.

A confusing case: pulmonary lesions including cavities, isolated left heart endocarditis and inferior vena cava thrombosis in a patient with perforated diverticulitis.

There are numerous causes of pulmonary cavitary lesions as infection (bacterial, parasitic and invasive fungal), Wegener granulomatosis (WG) and other vasculitis, sarcoidosis, malignancy, septic thromboembolism, airways disease (cystic bronchiectasis and bullae), pneumatoceles and traumatic parenchymal laceration. Herein, we present a case with perforated diverticulitis causing pulmonary cavitary lesions and a septic thrombus in the neighboring inferior vena cava.

Inoperable isolated cardiac hydatid cyst controlled with albendazole in an older adult with dementia

Hydatid cyst, a human parasitic disease, remains a clinical problem in undeveloped and developing countries. Although liver and lungs are regular sites of infection, rarely other organs such as the heart can be involved. Herein, we report an isolated cardiac hydatid cyst in an 87-year-old man. He had a history of dementia for 5 years and no history for cardiac or pulmonary disease. He presented with exertional dyspnoea which continued up to 6 months. The diagnosis was made by echocardiography and computed tomography (CT). The patient was inoperable and was treated with albendazole 10 mg/kg for 6 months. After a 6-month follow-up, echocardiography revealed reduction in the size of the cyst. We believe this is the first documented case of cardiac hydatid cyst which regressed with only medical treatment in an older adult with dementia.

Sole Infrequent Karyotypic Aberration Trisomy 6 in a Patient with Acute Myeloid Leukemia and Breast Cancer in Remission

Thank you very much for your valuable comments and sharing your experience. We agree for your contribution. In thalassemia patients, several transplantation centers categorised risk factors prior to allogenic hematopoietic stem cell transplantation. Pesaro classification assigned patients to three arms according to the absence or presence of one, two or three risk factors: hepatomegaly > 2 cm, portal fibrosis, and irregular chelation history [1]. It should be kept in mind that in a study by Ghavamzadeh et al., liver iron overload did not change after transplant (p=0.61) but hepatic fibrosis progressed (p=0.01) [2]. Allogeneic stem cell transplantation did not reduce liver iron overload and in fact liver fibrosis increased. Also steps for reducing iron overload should be taken in the post transplant setting [3]. Iron overload is still an essential issue in both pre and post transplant settings. Survival in transfusion-dependent thalassemia patients can be improved with proper understanding of the pathophysiology of thalassemia and iron toxicity.

Comparison of Myelodysplastic Syndrome Prognostic Scoring Systems.

Objective: Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease. Patients are at risk of developing cytopenias or progression to acute myeloid leukemia. Different classifications and prognostic scoring systems have been developed. The aim of this study was to compare the different prognostic scoring systems. Materials and Methods: One hundred and one patients who were diagnosed with primary MDS in 2003-2011 in a tertiary care university hospital’s hematology department were included in the study. Results: As the International Prognostic Scoring System (IPSS), World Health Organization Classification-Based Prognostic Scoring System (WPSS), MD Anderson Prognostic Scoring System (MPSS), and revised IPSS (IPSS-R) risk categories increased, leukemia-free survival and overall survival decreased (p<0.001). When the IPSS, WPSS, MPSS, and IPSS-R prognostic systems were compared by Cox regression analysis, the WPSS was the best in predicting leukemia-free survival (p<0.001), and the WPSS (p<0.001) and IPSS-R (p=0.037) were better in predicting overall survival. Conclusion: All 4 prognostic systems were successful in predicting overall survival and leukemia-free survival (p<0.001). The WPSS was found to be the best predictor for leukemia-free survival, while the WPSS and IPSS-R were found to be the best predictors for overall survival.

Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma

Objective: Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was to identify individual genes whose expression profiles match that of the one generated by cytotoxicity experiments for bortezomib. Materials and Methods: We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of metadata derived from relevant information. The E-MTAB-783 dataset containing expression data from 789 cancer cell lines including 8 myeloma cell lines with drug screening data from the Wellcome Trust Sanger Institute database obtained from ArrayExpress was “Robust Multi-array analysis” normalized using GeneSpring v.12.5. Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project. In order to identify individual genes whose expression profiles matched that of the one generated by cytotoxicity experiments for bortezomib, we used a linear regression-based approach, where we searched for statistically significant correlations between gene expression values and IC50 data. The intersections of the genes were identified in 8 cell lines and used for further analysis. Results: Our linear regression model identified 73 genes and some genes expression levels were found to very closely correlated with bortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways. Conclusion: The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.