Progressive Multifocal Leukoencephalopathy Among Ibrutinib Treatment In Chronic Lymphocytic Leukemia.

INTRODUCTION: Both chronic lymphocytic leukemia (CLL) itself and the drugs used for its treatment, pose a risk for progressive multifocal leukoencephalopathy (PML). Although the relationship between Rituximab and PML is well known, case reports that have been recently published, suggest that ibrutinib; which is used in the treatment of CLL, may increase the risk of PML. CASE REPORT: Here, we report a case of 64 year-old female patient with CLL who was previously treated with rituximab, fludarabine and bendamustin but developed PML after receiving monotherapy with ibrutinib. According to Naranjo's algorithm, the causality relationship with the drug is possible with a score of 3. The patient initially exhibited neurological symptoms. Magnetic resonance of the brain revealed a bilateral asymmetric hyperintensity in the white matter involving the parietal and occipital lobules, and there was no mass effect, edema, hemorrhagic or iscemic lesions. No enhancement of contrast media was observed. The findings were consistent with demyelination and suggestive of PML. MANAGEMENT AND OUTCOME: Mirtazapine treatment was initiated. However, neurological sympthoms continuously progressed over the following weeks and the patient, aged 64, died six weeks after diagnosis of PML. DISCUSSION: PML is a rare and often fatal demyelinating disease of the central nervous system (CNS) that is exclusively seen in immunocompromised patients and there is no specific agent to treat PML. The case discussed here, highlights that the use of ibrutinib in chronic lymphocytic leukemia (CLL) therapy may result in PML.

Determination of the relationship between mortality and SOFA, qSOFA, MASCC scores in febrile neutropenic patients monitored in the intensive care unit.

PURPOSE: Febrile neutropenia (FN) is a hematological emergency. It is challenging and confusing for the clinicians to make the decision of the febrile neutropenic patients under chemotherapy to be monitored at intensive care unit (ICU). The aim of this study was to define the factors supporting decision-making for the critical patients with febrile neutropenia. METHODS: The data of 60 patients, who were taken to the ICU while they were under treatment in the Hematology Clinic with a diagnosis of febrile neutropenia, were analyzed retrospectively, in order to identify clinically useful prognostic parameters. RESULTS: The ICU mortality rate was 80%. Mortality was significantly associated with higher sequential organ failure assessment score (SOFA), quick sequential organ failure assessment score (qSOFA), and hematological SOFA (SOFAhem) scores on admission. All cases having SOFA score 10 and above and qSOFA score 2 and above died. In multivariate analysis, qSOFA score was found to be statistically significant in predicting mortality in regard to ICU admission (p = 0.004). CONCLUSION: Mortality of febrile neutropenic patients admitted to ICU is high. It would be appropriate to determine the extent of organ dysfunction instead of underlying disease, for making the decision of ICU admission. It should be noticed that the risk mortality is high for the FN cases with SOFA score 10 or above, qSOFA score 2 or above, and in need of mechanical ventilation and positive inotropic support; hence, early intervention is recommended. In our study, the most significant parameter in predicting ICU mortality was found to be qSOFA.

Prognostic significance of bone marrow fibrosis in diffuse large B-cell lymphoma.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas. The aim of this study is to determine the relationship between the increase in the degree of fibrosis in the bone marrow and prognosis and mortality in newly diagnosed DLBCL. METHODS: Bone marrow biopsy of 153 newly diagnosed DLBCL patients was determined by staining with reticulin, Masson's trichrome histochemical stain, and the degree of fibrosis was determined. RESULTS: In the bone marrow biopsy performed at the time of diagnosis, bone marrow fibrosis (BMF) was observed in 70 patients. While BMF-1 was detected in 42 patients (60%), BMF-2 was detected in 25 patients (35%) and BMF-3 was detected in 3 patients (4%). As the degree of BMF increased, the median overall survival and median progression-free survival times were significantly shorter (p: 0.008), (p < 0.001). In patients with an increased degree of BMF, a significant decrease in leukocyte and neutrophil counts was observed after chemotherapy (p: 0.004). According to the results of the multivariate Cox regression model, it was determined that high NCCN-IPI risk (HR: 8.25; %95 CI: 1.09-62.52; p = 0.041) and being BMF ≥ 2 (HR: 3.75; %95 CI: 1.65-8.51; p = 0.002), increased the risk of death (p = 0.002, -2 loglikelihood = 392,553). CONCLUSION: When the literature was reviewed, it was seen that this study was the first to define that bone marrow fibrosis grade 2 and above in DLBCL is a prognostic marker associated with worse survival. In the bone marrow pathology, which is examined to detect advanced disease in DLBCL, besides lymphomatous involvement, the detection of fibrosis grade is very important.

Vascular calcification and growth arrest specific protein 6 levels in chronic renal failure / Calcificación vascular y detención de crecimiento de proteína específica 6 niveles en insuficiencia renal crónica

INTRODUCTION: Cardiovascular disease is the main cause of mortality and morbidity in chronic renal failure. It's known that vascular calcification (VC) and carotid intima media thickness (CIMT) are strongly associated with cardiovascular diseases. Growth arrest specific protein 6 (Gas6) is a vitamin K-dependent protein and regulates various processes such as proliferation, cell survival, migration and inflammation. Gas6 is known to protect endothelial cells and vascular smooth muscle cells against apoptosis by inhibiting Bcl-2 induced Caspase 3 activation. The relationship between Gas6 and cardiovascular diseases has been demonstrated in many mouse models and cell cultures. However, there are conflicting reports whether Gas6 levels are increasing or decreasing in human studies of diabetic and/or chronic renal failure. In present study the aim was to examine plasma Gas6 levels and its relation with CIMT and coronary artery calcification score (CACS) in chronic kidney disease (CKD) patients. METHODS: Total of 137 patients of which 32 chronic hemodialysis and 105 predialysis patients as well as 73 healthy controls were enrolled in the study. Human Gas6 levels in serum samples were studied by ELISA method. CIMT was measured by ultrasonography. CACS was measured by multislice computed tomography. RESULTS: The mean age was 54.37±16.61 years in dialysis group, 55.20±14.80 years in predialysis group and 53.26±9.04 years in control group. Serum creatinine was 0.78±0.16 mg/dl in the control group and 1.96±1.64 mg/dl in the predialysis group and 5.94±1.55 mg/dl in the dialysis group. 24 hours urine protein levels were significally higher in the dialysis group than the predialysis and the control group. CIMT values were similar in predialysis and dialysis groups. These values were significantly higher than the control group. Although CACS was higher in dialysis group than predialysis and control group, the results were not statistically significant since the distribution range was very wide. Gas6 was 98.84±53.32 ng/mL in the control group and statistically higher than the dialysis (63.85±38.92 ng/mL) and the predialysis groups (54.96±38.49 ng/mL) (p=0.001). Gas6 levels were lower in diabetic patients than non-diabetics (53.69±35.26 ng/mL, 69.26±47.50 ng/mL, p=0.023, respectively). Negative correlation was detected between Gas6 and age, BMI, CACS, carotid IMT and proteinuria. In the logistic regression analysis, Gas6 remained significantly associated with BMI, CIMT and proteinuria. CONCLUSION: In our study, a negative correlation of Gas6 with BMI, CACS, CIMT and proteinuria and lower Gas6 levels in diabetic patients support that decreased Gas6 levels in chronic renal failure may have a role in vascular calcification through altered glucose tolerance, chronic inflammation, endothelial dysfunction and increased apoptosis. Our study has an importance because it is the first study showing a relation between Gas6 and proteinuria, CACS and carotid IMT in patients with chronic renal failure

INTRODUCCIÓN: La enfermedad cardiovascular es la principal causa de mortalidad y morbilidad en la insuficiencia renal crónica. Se sabe que la calcificación vascular (CV) y el grosor de la íntima-media de la carótida (CIMT, por sus siglas en inglés) están vinculados de forma muy estrecha con enfermedades cardiovasculares. La proteína específica del gen 6 de la detención de crecimiento (Gas6) es una proteína dependiente de la vitamina K y regula diversos procesos, como la proliferación, la supervivencia celular, la migración y la inflamación. La proteína Gas6 es conocida por proteger las células endoteliales y las células musculares lisas vasculares contra la apoptosis mediante la inhibición de la activación de la caspasa-3 inducida por la proteína Bcl-2. Se ha demostrado la relación entre la Gas6 y las enfermedades cardiovasculares en muchos modelos de ratones y cultivos celulares. Sin embargo, existen informes contradictorios acerca de si los niveles de Gas6 aumentan o disminuyen en estudios de humanos con insuficiencia renal crónica y/o diabética. En este estudio, el objetivo fue examinar los niveles plasmáticos de Gas6 y su relación con el CIMT y la puntuación de calcificación de las arterias coronarias (CACS, por sus siglas en inglés) en pacientes con enfermedad renal crónica (ERC). MATERIAL Y MÉTODOS: Un total de 137 pacientes fueron incluidos en el estudio, de los cuales 32 estaban en hemodiálisis crónica, 105 en prediálisis, y 73 pacientes representaban controles sanos. Se esudiaron los niveles de Gas6 en muestras de suero mediante el método ELISA. El CIMT se midió por medio de ecografía. La CACS se midió mediante tomografía computarizada multicorte. RESULTADOS: La edad media fue de 54,37 ± 16,61 años en el grupo de diálisis; 55,20 ± 14,80 años en el grupo de prediálisis, y 53,26 ± 9,04 años en el grupo de control. La creatinina sérica fue de 0,78 ± 0,16 mg/dl en el grupo de control; 1,96 ± 1,64 mg/dl en el de prediálisis, y 5,94 ± 1,55 mg/dl en el de diálisis. Las concentraciones de proteína en orina de 24 horas fueron significativamente más altas en el grupo de diálisis que en los de prediálisis y control. Los valores del CIMT fueron similares en los grupos de prediálisis y de diálisis. Estos valores fueron considerablemnete más altos que en el grupo de control. Aunque la CACS fue más alta en el grupo de diálisis que en los otros dos, los resultados no fueron estadísticamente significativos, ya que el rango de distribución fue muy amplio. La proteína Gas6 fue de 98,84 ± 53,32 ng/ml en el grupo de control y estadísticamente más alta que en los grupos de diálisis (63,85 ± 38,92 ng/ml) y de prediálisis (54,96 ± 38,49 ng/ml) (p = 0,001). Los niveles de Gas6 fueron más bajos en los pacientes diabéticos que en los no diabéticos (53,69 ± 35,26 ng/ml; 69,26 ± 47,50 ng/ml, [p = 0,023], respectivamente). Se detectó una correlación negativa entre la proteína Gas6 y la edad, el IMC, la CACS, el CIMT y la proteinuria. En el análisis de regresión logística, la Gas6 se mantuvo estrechamente relacionada con el IMC, el CIMT y la proteinuria. CONCLUSIÓN: En nuestro estudio, la correlación negativa de Gas6 con IMC, CACS, CIMT y proteinuria, y los niveles más bajos de Gas6 en pacientes diabéticos sustentan la idea de que la disminución de los niveles de Gas6 en la insuficiencia renal crónica puede jugar un papel en la calcificación vascular a través de la tolerancia alterada a la glucosa, la inflamación crónica, la disfunción endotelial y el aumento de la apoptosis. La importancia de nuestro estudio radica en que es el primero que muestra una relación entre la Gas6 y la proteinuria, la CACS y el CIMT en pacientes con insuficiencia renal crónica