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.

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.

A chronic myeloid leukemia case with a variant translocation t(11;22) (q23;q11.2): masked Philadelphia or simple variant translocation?

Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia chromosome (Ph), usually due to a reciprocal translocation, t(9;22)(q34;q11.2). The remaining cases (2-10%) have variant translocation, and more rarely (~1%) a cryptic rearrangement is present which can be detected by fluorescence in situ hybridization analysis in a CML patient with a Ph-negative karyotype (Masked Ph). We present a masked/variant BCL-ABL-positive CML patient showing a t(11;22)(q23;q11.2) which was detected using a combined approach of conventional cytogenetics and reverse transcription polymerase chain reaction. In February 2013, the patient was diagnosed as having CML. Imatinib mesylate (400 mg/day), was then started. Under imatinib therapy a complete hematologic and cytogenetic response was attained. In December 2013, an increment in BCR-ABL/ABL transcript levels according to the International Scale (from 0.0471% to 1.4034%), indicating imatinib failure, was documented. Administration of nilotinib (400 mg twice daily) resulted in durable molecular response after 3 months. The patient is still on nilotinib treatment throughout the observation period with no sign of recurrence and adverse events.

Chronic lymphocytic lymphoma and concomitant renal cell carcinoma (Clear Cell Type): Review of the literature.

In the present report, a 73 years-old male patient who developed clear cell type renal cell carcinoma (RCC) 5 years after the diagnosis of chronic lymphocytic lymphoma (CLL) and plausible explanations for this association were discussed by the authors. The incidence of CLL and RCC occurring in the same patient is higher than that expected in the general population. Various explicative hypotheses of this concurrence include treatment-related development of a second malignancy, immunomodulatory mechanisms, viral aetiology, cytokine (interleukin 6) release from a tumor, and common genetic mutations. Further investigations are warranted.

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.

An unexpected and devastating adverse event of dasatinib: Rhabdomyolysis.

We, herein, describe a 52-year-old male whom developed rhabdomyolysis and acute renal failure likely related to dasatinib shortly after the administration of treatment. After withdrawal of dasatinib, the myalgia reduced, and his CK returned to normal levels within a week. On follow-up acute renal failure did resolve without requiring dialysis, but unfortunately the patient died of severe respiratory distress. We recommend that musculoskeletal symptoms should be monitorized during therapy with dasatinib, and CML patients with musculoskeletal symptoms should have CK levels checked in order to prevent this unexpected but devastating adverse event.

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.

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

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.

High frequency of autonomous T-cell proliferation compatible with T-cell large granular lymphocytic leukemia in patients with cytopenia of unknown etiology.

Large granular lymphocytic leukemia/lymphoproliferative disorder (LGL-L/LPD) is a heterogeneous neoplastic disease of large granular lymphocytes and is a well-known cause of cytopenias. We aimed to reveal the incidence of LGL-L/LPD in patients with cytopenia(s) of unknown etiology (CUE). Twenty-eight patients with CUE were investigated for LGL-L/LPD. T-cell LGL leukemia (LGL-L) was diagnosed in 12 (42.9 %) patients. The frequencies of LGL-L in patients who had anemia, neutropenia, and thrombocytopenia were 9/14 (64.2 %), 11/23 (47.8 %), and 3/10 (30 %), respectively. Seventeen of the 28 patients met the criteria of idiopathic cytopenia of undetermined significance (ICUS), and LGL-L was found in six (35.3 %) of them. We conclude that LGL-L is a rather common disease in patients with CUE and ICUS. It should be considered in this patient group and investigated thoroughly.

Clinical and pathological correlations of marrow PUMA and P53 expressions in myelodysplastic syndromes.

p53 is a key regulator of apoptosis. p53 upregulated modulator of apoptosis (PUMA) is a critical mediator of p53-dependent and independent apoptosis. The objective of this study was to evaluate the relationship of p53 and PUMA to the prognosis of MDS. Bone marrow biopsies of MDS patients at the time of diagnosis (n = 76) and at the time of transformation (n = 19) were included in the study group. The expression of p53 and PUMA was evaluated using immunohistochemistry. When compared to the control group, both p53 (p < 0.001) and PUMA (p = 0.012) expression levels were significantly higher in MDS group. In MDS group, there was a moderate positive correlation between p53 and PUMA expressions. PUMA expression was not correlated with event free and overall survival. However, overall survival was significantly lower in cases with p53 expression in more than 50% of the cells. There was an increase in PUMA expression in cases that showed transformation as compared to the initial diagnostic bone marrows but was not statistically significant. The correlation that existed between p53 and PUMA was lost in transformed cases. Our results showed that PUMA and p53 expressions are increased in MDS marrows compared to normal marrows. PUMA expression increases further during transformation while the expression of p53 is not significantly altered which suggests that PUMA alterations might be a late event during the evolution of MDS.

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.

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.

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.

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.