Hematological Indices May Be Useful in the Diagnosis of Systemic Lupus Erythematosus and in Determining Disease Activity in Behçet's Disease.

OBJECTIVES: The aim of this study was to investigate the relationships between clinical features of rheumatic diseases and hematologic indices, including mean platelet volume (MPV), MPV/platelet ratio (MPR), platelet/lymphocyte ratio, and neutrophil/lymphocyte ratio (NLR). Subjects andMethods: Rheumatoid arthritis (RA; n = 91), systemic lupus erythematosus (SLE; n = 51), systemic sclerosis (SSc; n = 39), and Behçet's disease (BD; n = 53) patients, and 55 healthy controls (HC) were enrolled. Hematological indices were calculated and one-way analysis of variance, Mann-Whitney U and χ2 tests, and receiver operating characteristic (ROC) analyses were performed. RESULTS: The MPV and MPR were higher in the SLE group than the RA group (p < 0.05 and p < 0.01, respectively). ROC analysis indicated that MPV (area under the curve, AUC, 0.68, 95% CI 0.58-0.77) and MPR (AUC 0.69, 95% CI 0.59-0.78) were sensitive and specific markers for SLE against RA. The NLR was higher in the RA, SLE, and SSc groups compared to the HC group (p < 0.05, p < 0.001, and p < 0.01, respectively). The NLR was higher in the active BD patients than those that were inactive (p = 0.008). Besides, NLR was higher in patients with neuro-BD and patients with active genital ulcers compared to patients without neurological involvement (p < 0.01) and active genital ulcers (p < 0.05). CONCLUSION: The MPV and MPR were significantly higher in the SLE group than in the RA group. They were also higher in the active than in the inactive BD patients. The MPV and MPR are useful diagnostic tools for SLE, and NLR reflects disease activity in BD. However, further research should be performed to standardize these tools.

Effect of ethinyl estradiol-cyproterone acetate treatment on asymmetric dimethyl-arginine levels in women with polycystic ovary syndrome.

PURPOSE: Our study was undertaken to evaluate the levels of asymmetric dimethyl-arginine (ADMA) in a group of patients affected with polycystic ovary syndrome (PCOS)--under ethinyl estradiol-cyproterone acetate treatment or not--as compared with a group of healthy controls. METHODS: Fifty-eight women with PCOS and 45 patients as control group were included in the study. The 58 women with PCOS were separated into two groups: Group A (n = 29) were treated with an oral contraceptive pill containing 0.035 mg of ethinyl estradiol (EE) and 2 mg of cyproterone acetate (CA) (Diane-35) for 6 months. Group B (n = 29) did not take any drug. Group C (n = 45) was healthy women as control group. Serum levels of ADMA, lipid and glucose metabolism parameters, hormone profile were measured on the sixth month of treatment. RESULTS: ADMA levels were similar in women with PCOS and controls, whereas ADMA levels significantly decreased after a period of 6 months treatment with EE + CA in women with PCOS. ADMA levels and insulin resistance were decreased with treatment. However, patients with PCOS had significantly higher total cholesterol and Low-density lipoprotein cholesterol (LDL-C) compared to controls, treatment with EE + CA did not provide any improvement on lipid parameters. CONCLUSION: Serum ADMA levels and insulin resistance were lower in PCOS group treated with EE + CA than control group.

Local Renin-Angiotensin system in normal hematopoietic and multiple myeloma-related progenitor cells.

OBJECTIVE: The prominent functions of the local renin-angiotensin system (RAS) in primitive hematopoiesis further support the hypothesis that local autocrine bone marrow RAS could also be active in neoplastic hematopoiesis. The aim of this study is to examine critical RAS elements in normal CD34+ hematopoietic stem cells and multiple myeloma (MM)-related progenitor cells. MATERIALS AND METHODS: The study group comprised the total bone marrow cells (CBM) of 10 hematologically normal people, the CD34+ stem cell samples (CD34+CBM) of 9 healthy donors for allogeneic peripheral stem cell transplantation, and the CD34+ stem cell samples (CD34+MM) of 9 MM patients undergoing autologous peripheral stem cell transplantation. We searched for the gene expression of the major RAS components in healthy hematopoietic cells and myeloma cells by quantitative real-time polymerase chain reaction analysis. RESULTS: RENIN, angiotensinogen (ANGTS), and angiotensin converting enzyme-I (ACE I) mRNA expression levels of CBM were significantly higher than those in myeloma patients (p=0.03, p=0.002, and p=0.0008, respectively). Moreover, RENIN and ANGTS mRNA expression levels were significantly higher in CD34+ stem cell samples of healthy allogeneic donors compared to those in myeloma patients (p=0.001 and p=0.01). However, ACE I expression levels were similar in CD34+CBM and CD34+MM hematopoietic cells (p=0.89). CONCLUSION: Although found to be lower than in the CBM and CD34+CBM hematopoietic cells, the local RAS components were also expressed in CD34+MM hematopoietic cells. This point should be kept in mind while focusing on the immunobiology of MM and the processing of autologous cells during the formation of transplantation treatment protocols.

Hyper-CVAD regimen in routine management of adult acute lymphoblastic leukemia: a retrospective multicenter study.

Treatment of acute lymphoblastic leukemia is unsatisfactory in adults due to disease and patient-related factors and probably because adult chemotherapy regimens are weaker than pediatric protocols. Worries about inadequacy of adult regimens urged many hematologists, including us, to reconsider their routine treatment practices. In this retrospective multicenter study, we aimed to evaluate results of hyper-CVAD treatment in comparison to other intensive protocols. All patients aged ≤65 years who were commenced on intensive induction chemotherapy between 1999 and 2011 were included in the study. Sixty-eight of 166 patients received hyper-CVAD, 65 were treated with CALGB-8811 regimen and 33 with multiple other protocols. Limited number of patients who were treated with other intensive protocols and mature B-acute lymphoblastic leukemia cases who were mostly given hyper-CVAD were eliminated from the statistical analyses. In spite of a favorable complete remission rate (84.2%), overall (26.3 vs. 44.2% at 5 years, p = 0.05) and disease-free (24.9 vs. 48.2%, p = 0.001) survival rates were inferior with hyper-CVAD compared to CALGB-8811 due to higher cumulative nonrelapse mortality risk (29.7 vs. 5.9%, p = 0.003) and no superiority in cumulative relapse incidence comparison (45% for both arms, p = 0.44). Hyper-CVAD, in its original form, was a less favorable regimen in our practice.

Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic hematopoietic stem cell transplantation for acute leukemia patients: a single center experience.

Due to the high transplant related morbidity and mortality (TRM), relatively younger acute leukemia patients that have a good performance status and no comorbidity are eligible for myeloablative conditioning (MAC) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcomes of 84 consecutive adult patients with ALL (n=38) or AML (n=46) who underwent allo-HSCT from their HLA-identical siblings were evaluated retrospectively. The median age at transplantation was 34 (17-58 years) for the whole patient population. Of these, 24 patients received a MAC and 60 patients received a fludarabine-based reduced intensity conditioning regimen (RIC). After a median follow-up of 32 months (range, 1-119), for the entire group, the 3-year estimated overall survival (OS) was 57.5% and the disease-free survival (DFS) was 51.5%. The OS for ALL and AML patients were 53.9% vs 62.1%: and DFS were 50.5% and 53.4%, respectively. The 3-year estimated OS for RIC and MAC patients were 63.2% and 41.7%; and DFS were 57.1% and 34.7%, respectively. In ALL patients, conditioning regimens (RIC vs MAC) led to similar OS and DFS; however, in AML patients both OS (70.1% vs 21.4%) and DFS (59.3% vs 42.9%) were found to be higher in RIC patients compared to MAC recipients. Overall, the TRM at day 100 was 1.7% and has increased up to 5.1% at 1st year. In multivariate analysis, the diagnosis (p=0.03) and RIC regimen (p=0.027) were the prognostic variables for prolonged OS in all patients; and RIC regimen (p=0.031) was the only prognostic factor for prolonged OS in AML patients. The first complete remission (CR1) was correlated with a prolonged DFS as an independent variable for all patients (p=0.09). Eleven of the RIC patients (18.3%) and 6 of the MAC patients (25%) developed acute graft-versus-host disease (GvHD). Seventeen of the RIC patients (33.3%) and 4 of the MAC patients (16.7%) developed chronic GvHD. In conclusion, RIC conditioning regimens may provide a longer OS and DFS, especially in patients with AML who are in first CR, not eligible for MAC conditioning.

Co-expression of t(15;17) and t(8;21) in a Case of Acute Promyelocytic Leukemia: Review of the Literature.

UNLABELLED: Additional chromosomal abnormalities in acute myelogenous leukemia have been identified as one of the most important prognostic factors. Favorable chromosomal changes such as t(8;21), inv(16), and t(15;17) are associated with higher rates of complete remission and event-free survival. Translocation (15;17) characterizes acute promyelocytic leukemia (APL) (French-American-British class M3) in almost all patients. Secondary chromosomal abnormalities are also present in approximately 23%-29% of patients with newly diagnosed APL. The prognostic implications of t(8;21) and other secondary cytogenetic aberrations in APL are reviewed here. We present a 47-year-old woman diagnosed with APL whose initial cytogenetic analysis included both t(8;21) and t(15;17). The initial induction chemotherapy included 3 days of idarubicin (12 mg/m2/day) and daily all-trans retinoic acid (ATRA; 45 mg/m2/day). At the sixth week of treatment, a control bone marrow biopsy was found to be normocellular, t(15;17) bcr3 and t(8;21) were negative, and t(15;17) bcr1 fusion transcripts were reduced from 5007 (1.78525699%) copies per 1 µg RNA to 40 (0.00062020%) with real-time quantitative polymerase chain reaction. Consolidation with 4 days of idarubicin (5 mg/m2/day), ATRA (45 mg/m2/day for 15 days), and cytarabine (1 g/m2/day for 4 days) was then started. However, the patient became pancytopenic and had neutropenic fever after consolidation treatment. Unfortunately, she died 3 months after the time of APL diagnosis, due to acute respiratory distress syndrome-like respiratory problems and multiorgan dysfunction requiring respiratory support and hemodialysis. CONFLICT OF INTEREST: None declared.

Turkish Chronic Myeloid Leukemia Study: Retrospective Sectional Analysis of CML Patients.

OBJECTIVE: here have been tremendous changes in treatment and follow-up of patients with chronic myeloid leukemia (CML) in the last decade. Especially, regular publication and updating of NCCN and ELN guidelines have provided enermous rationale and base for close monitorization of patients with CML. But, it is stil needed to have registry results retrospectively to evaluate daily CML practices. MATERIALS AND METHODS: In this article, we have evaluated 1133 patients' results with CML in terms of demographical features, disease status, response, resistance and use of second-generation TKIs. RESULTS: The response rate has been found relatively high in comparison with previously published articles, and we detected that there was a lack of appropriate and adequate molecular response assessment. CONCLUSION: We concluded that we need to improve registry systems and increase the availability of molecular response assessment to provide high-quality patient care. CONFLICT OF INTEREST: None declared.

Nasal Natural Killer/T-cell Lymphoma with Skin, Eye, and Peroneal Nerve Involvement.

UNLABELLED: Nasal-type natural killer (NK)/T-cell lymphoma (NKTL) is a rare disease strongly associated with Epstein-Barr virus and is often localized to the upper aerodigestive tract at presentation. Extranodal NKTL may involve any extranodal site and disease beyond the nasal cavity is highly aggressive, with short survival time and poor response to therapy. Herein we present a 57-year-old male that had been treated with systemic chemotherapy and cranial radiotherapy for nasaltype NKTL in the palate with skin, right eye, and right peroneal nerve involvement. He was given salvage chemotherapy consisting of 3 cycles of ICE and his response to the therapy was satisfactory, except for persistent right drop foot. About 6 weeks later, the patient presented with bilateral total loss of vision and proptosis; therefore, DHAP chemotherapy was started. Unfortunately, after 1 cycle of the second salvage chemotherapy, he died due to severe fungal infection of the hard palate. Despite the fact that involvement of any extranodal site is possible, concurrent involvement of many systems in NKTL patients is unusual. Nasal-type NKTL has a poor prognosis, despite local radiotherapy and systemic chemotherapy. Physicians should be aware of this rare disorder than can only be diagnosed after extensive immunohistochemical studies. CONFLICT OF INTEREST: None declared.

Anxiety, Depression and Burnout Levels of Turkish Healthcare Workers at the End of the First Period of COVID-19 Pandemic in Turkey.

OBJECTIVE: COVID-19 pandemic affected the mental health of healthcare workers (HCWs) as well as their physical health. In this study, we aimed to evaluate the anxiety, depression and burnout levels of Turkish HCWs after the first period of the pandemic. METHODS: The participants filled sociodemographic data form, Hospital Anxiety and Depression Scale (HADS) and Maslach Burnout Inventory (MBI). RESULTS: In this study, 221 HCWs (68.8% female) with a median age of 28 (20-66) years were included. Concerning HADS cut-off points, 39.8% of the participants scored above the depression cut-off point, while 26.2% scored above the cut-off point for anxiety. The anxiety (HADS-A) and depression (HADS-D) scores of nurses and medical secretaries were significantly higher than the physicians. Also, the anxiety and depression rates of nurses were higher than both physicians and medical secretaries. Emotional exhaustion (MBI-EE) and depersonalization (MBI-D) scores were highest in nurses, followed by medical secretaries and physicians, respectively. In multivariate analysis, being a nurse (OR: 4.671, p = 0.044) or medical secretary (OR: 4.013, p = 0.048), requirement of using a mental health support line (OR: 4.641, p = 0.005), having any kind of addiction (OR: 2.562, p = 0.019) and being under antidepressant therapy (OR: 3.096, p = 0.036) significantly increased the risk of anxiety. However, in multivariate analyses, the only requirement of using a mental health support line significantly increased the risk of depression (OR: 8.542, p = 0.001). CONCLUSION: Female HCWs, nurses and medical secretaries experienced higher levels of mental health symptoms than male HCWs and physicians.

Effects of erdosteine on cyclosporine-A-induced hepatotoxicity in rats.

Cyclosporine A (CsA) is a potent immunosuppressive agent used for organ transplantations and various autoimmune disorders. However, hepatotoxicity due to CsA remains one of the major side effects. The use of antioxidants reduces the adverse effects of CsA. The aim of this study was to determine the protective effects of erdosteine on CsA-induced liver injury through tissue oxidant/antioxidant parameters and to evaluate light microscopic alterations in rat-liver tissues. Rats were randomly divided into four experimental groups: The control group received sunflower oil (2 mL/kg/day, per orally; p.o.), while the other groups were treated with CsA (25 mg/kg/day, p.o.) or erdosteine (10 mg/kg/day, p.o.) or CsA+erdosteine, respectively. Serum aspartate aminotransferase and alanine aminotransferase levels, tissue malondialdehyde and nitric oxide levels, and superoxide dismutase, glutathione peroxidase and catalase enzyme activities were measured. Histological examination was performed. CsA caused a significant deterioration in the hepatic function tests, morphology, and gave rise to severe oxidative stress in the liver. Erdostein significantly improved the functional and histological parameters and attenuated the oxidative stresss induced by CsA. Erdostein protects liver tissue against oxygen free radicals and prevents hepatic dysfunction and morphological abnormalities associated with chronic CsA administration.

Eculizumab before and after allogeneic hematopoietic stem cell transplantation in a patient with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the triad of intravascular hemolysis, venous thrombosis, and cytopenia. Treatment of PNH is generally supportive. Bone marrow transplantation is the only curative therapy for PNH, but is associated with significant morbidity and mortality. Herein, we present a patient with PNH that received eculizumab, a humanized monoclonal antibody that blocks activation of the terminal complement at C5, before and immediately following allogeneic peripheral stem cell transplantation. Prior to hematopoietic stem cell transplantation eculizumab treatment markedly reduced hemolysis and transfusion requirement; however, 1 d post transplantation a hemolytic episode occured, which was successfully stopped with eculizumab re-treatment. Afterwards the patient did not require additional transfusions. The results of this study indicate that early administration of eculizumab may be a safe and effective therapy for hemolytic episodes associated with allogeneic peripheral stem cell transplantation in patients with PNH.

The effects of L-carnitine therapy on respiratory function tests in chronic hemodialysis patients.

BACKGROUND: Respiratory functions are affected during hemodialysis. The strength of respiratory muscles, ultrafiltration rate, and acid-base balance have been suggested as important factors. L-carnitine is crucial for energy producing, utilization of fatty acid, and possible amino acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and especially by its loss during dialysis. This study was performed to investigate the chronic effects of L-carnitine treatment on respiratory functions in adults receiving chronic hemodialysis therapy. METHODS: A total of 20 hemodialysis patients were scheduled to take L-carnitine supplementation (20 mg/kg three times/week) (group 1), and the rest of 20 hemodialysis patients served as the control group and were observed without supplementation with L-carnitine (group 2). Pre- and post-dialytic L-carnitine levels and post-dialytic respiratory functions tests were performed in both groups at baseline and after six months. RESULTS: The average concentration of free and total carnitine levels increased significantly after six months of supplementation (p < 0.01). While a statistically significant increase between postdialytic forced expiratory volume in one second/forced vital capacity values after treatment period (77.10 +/- 12.15 and 83.00 +/- 14.49, before and after treatment, respectively, p < 0.05) was observed, the increase of vital capacity, forced expiratory volume in one second, and forced expiratory flow between 25-75% of expired vital capacity were not significant in the treatment group (p > 0.05). CONCLUSION: Intravenous L-carnitine supplementation could contribute to the management of respiratory dysfunction in chronic hemodialysis patients by improving FEV1/FVC. The mechanism by which LC causes these effects merits further investigation.

Moxifloxacin-Induced Visual Hallucinations, Alterations in Mood and Behavior, and Hyperglycemia.

Visual hallucinations are sensory perceptions that occur without external stimuli. Moxifloxacin-induced visual hallucinations are very rarely reported (<0.1%). We describe a 66-year-old woman, without any known neuropsychiatric disorder or illicit drug abuse, who experienced complex visual hallucinations, mood, and behavioral alterations secondary to peroral 1 dose of moxifloxacin treatment that persisted for approximately 36 hours. In addition, a sudden increase in her blood glucose level was noted which also improved a few days after discontinuation of moxifloxacin treatment. Although very rare, it should be kept in mind that moxifloxacin may coincidentally induce neuropsychiatric adverse effects and hyperglycemia. Clinicians should be alert to recognize such uncommon offending adverse drug reactions.

Association of visceral fat accumulation and adiponectin levels with colorectal neoplasia.

PURPOSE: There are few studies addressing the association between measured values of visceral fat accumulation (VFA), adiponectin, and colorectal neoplasia. Our purpose is to investigate the association of VFA and serum adiponectin levels with colorectal adenoma and carcinoma patients. For this purpose, 54 patients with colorectal adenoma and carcinoma, diagnosed by colonoscopic evaluation, and 50 healthy control subjects were included. Patients were subjected to measurement of VFA and adiponectin level and calculation of insulin resistance. RESULTS: Patients with colorectal carcinoma had lower plasma adiponectin levels compared with controls. VFA level did not differ between patients and controls. Adiponectin level was found to be uncorrelated with VFA in the colorectal cancer and adenoma group. No correlation was found between insulin resistance and plasma adiponectin level and VFA. CONCLUSION: Our findings suggest that decreased plasma adiponectin level may be a factor involved in the development of colon cancer or a secondary effect of the metabolic derangements in colorectal cancer.

Prevalence of proximal neoplasms among asymptomatic patients according to distal colorectal findings.

Colorectal cancer has been described in association with hyperplastic polyposis. Only half of proximal colon cancers are associated with distal adenomas. To compare the prevalence of proximal and advanced neoplasia between patients with distal hyperplastic polyps only; with distal adenomas with or without hyperplastic polyps; and with no distal polyps, we retrospectively analyzed data of 1,064 adults who underwent colonoscopy. Of these patients, 3% had neoplasia. Proximal neoplasia occurred in 0.8% of 945 patients with no distal polyps, compared to none of 19 with distal hyperplastic polyps (P > 0.05) and 6% with distal adenomas (P > 0.05). Proximal advanced neoplasia occurred in 0.6% patients with no distal polyps, compared with none with distal hyperplastic polyps (P > 0.05) and 6% with distal adenomas (P > 0.05). In conclusion, patients with distal hyperplastic polyps, unlike those with distal adenomas, do not exhibit an increased risk for proximal neoplasia or proximal advanced neoplasia compared to those with no distal polyps.