Possible relation between expression of circulating microRNA and plasma cytokine levels in cases of pulmonary tuberculosis.

INTRODUCTION: Tuberculosis (TB) is a life-threatening infection and early diagnosis is critical for treatment and prevention of transmission. There is evidence of correlation between miRNA expression and cytokine regulation during TB infection. The aim of this study was to determine the relationship between expression levels of miRNAs in plasma and cytokine levels as a potential biomarker for genetic predisposition and/or early diagnosis of TB infection. METHODOLOGY: The expression levels of 86 miRNAs were examined in plasma samples of 44 TB patients and 44 healthy controls by qRT-PCR using BioMarkTM 96.96 Dynamic Array (Fluidigm Corporation, South San Francisco, CA, USA) system. The levels of plasma TNF-α, IFN-γ, IL-1ß, IL-4, IL-6, IL-8, IL-10, and IL-12/P40 were examined with ELISA. RESULTS: We identified dysregulation of 18 miRNAs which included upregulation of miR-1, miR-7-5p, miR-9-5p, miR-10a-5p, miR-10b-5p, miR-100-5p, miR-106b-5p, miR-128-3p, miR-133a-3p, miR-143-3p, miR-193a-5p, miR-200b-3p, miR-205-5p, miR-210-3p, and miR-296-5p, and downregulation of miR-15b-5p, miR-16-5p, and miR-25-3p in plasma samples of patients with pulmonary TB (p < 0.05). A significant correlation between the expression levels of miR-1, miR-7-5p, miR-9-5p, miR-10a-5p, miR-10b-5p, miR-15b-5p, miR-100-5p, miR-143-3p, miR-193a-5p, miR-200b-3p, miR-210-3p and cytokine levels of TNF-α, IFN-γ, IL-1ß, IL-8 and IL-10 was identified (p < 0.05). CONCLUSIONS: We demonstrated that altered expression levels of plasma miRNAs consistent with immunological response have the potential to serve as non-invasive biomarkers for early diagnosis of pulmonary TB. Additional investigations with larger sample sizes will be required to confirm our findings and to determine if miRNAs can be possible targets for TB management strategies.

Integration of low muscle mass into the IPS system and its prognostic significance in patients with Hodgkin's lymphoma.

Aim: The aim of this study is to determine whether a novel prognostic score can be obtained by including low muscle mass in the international prognostic score (IPS) system. Materials & Methods: Psoas muscle areas were determined in the PET/CT scans of the patients taken for staging at the time of diagnosis and after two cycles of ABVD. After evaluating the effect of low muscle mass on overall survival, receiver operating characteristic (ROC) analyzes were performed by including it in IPS systems. Results: Overall survival was significantly lower in patients with low muscle mass. Adding low muscle mass to IPS scores increased AUC, sensitivity and specificity. Conclusion: The integration of low muscle mass into the IPS scoring systems increased the success of these systems in predicting a prognosis.

Lay abstract Hodgkin's lymphoma is a cancer that responds well to standard treatments. However, the cancer recurs 30% of the time. Improved scoring systems could help better predict the outcomes of treatment. The 'International Prognostic Score' (IPS) system is an algorithm currently used to predict the possibility of death and treatment complications. In this study, low muscle mass is evaluated as data that could be added to the current scoring system to improve the system's ability to predict outcomes. Data from the scans of patients before and after treatment were used to determine the muscle mass. It was found that survival was significantly lower in patients with low muscle mass. This suggests that this information is highly effective in predicting the outcomes of Hodgkin's lymphoma patients.

Use of gemtuzumab ozogamicin in relapsed refractory acute myeloid leukemia: Multi-center real life data from Turkey.

We retrospectively evaluated the use of gemtuzumab ozogamicin (GO) in relapsed refractory (R/R) acute myeloid leukemia (AML) patients. Twenty-one CD33 positive R/R AML patients who received GO as a single agent in 4 hematology centers were included in this study. The median age was 59, and the median ECOG performance score was 2. According to cytogenetic analysis, 1 patient had favorable risk, 12 patients with intermediate, and 8 patients with adverse risk. The overall response rate was 52.3%. Partial response was achieved in 3 of 8 patients with adverse risk. 33.3% of patients developed grade 3 anemia. Grade 4 neutropenia and thrombocytopenia were observed in 80% of the patients. One of the patients died due to sinusoidal obstruction syndrome / veno-occlusive disease (SOS / VOD) due to GO side effects. GO may be considered as a good option for salvage therapy in R/R AML patients.

Patient-controlled analgesia and morphine consumption in sickle cell anemia painful crises: A new protocol.

OBJECTIVES: The sudden and rapidly increasing severity of pain in sickle cell anemia painful crises frequently requires the use of strong opioids. Patients require continuous administrations of various doses (increased/decreased) within the following hours. This study aims to retrospectively evaluate the effects of a structured protocol based on standardized Visual Analogue Scale (VAS) and Patient-controlled analgesia (PCA) patient demand count on morphine consumption in painful crises. METHODS: A total of 177 painful crises of 93 patients who were administered morphine using the PCA method according to appropriate analgesia protocol between 2004-2018 were evaluated in this study. The demographic data, hemoglobin chromatography and genotypes, painful episode follow-up time, VAS scores before and after treatment, and daily morphine consumption of the patients were recorded. Morphine consumption during the crisis according to age groups and sex were compared. RESULTS: Of the patients, 57% were homozygous hemoglobin type SS (HbSS). Mean morphine consumption with PCA method was 56.9±35.4 mg (min-max: 10-232 mg) and mean follow-up time was 3.4±2.1 days (min.-max.: 1-11). VAS scores were significantly lower after treatment (6.8±2.3 pre-treatment; 0.8±0.6 post-treatment) (p<0.05). CONCLUSION: To our knowledge, our study is the first structured protocol based on VAS and PCA demand data. We believe lower morphine dosage using PCA protocol according to the rapidly changing pain levels of the patients will provide effective analgesia. Prospective studies with fewer limitations will more effectively demonstrate the effectiveness of this protocol.

Study for the diagnostic screening of paroxsymal nocturnal hemoglobinuria in Turkey: Prospective multicentric evaluation of suspected patients.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease presenting with variable and various clinical findings. PNH might be overlooked and diagnosis may be delayed due to low awareness about PNH. This is the first multicenter study in Turkey, investigating the efficiency of diagnostic screening of PNH by multiparameter flow cytometry (FCM) according to consensus guidelines. METHODS: We evaluate the efficiency of consensus clinical indications for PNH testing with FCM in 1689peripheral blood samples from 20 centers between January 2014 and December 2017. RESULTS: Overall, at the 20 centers contributing to this study, PNH clone were detected in 62/1689 samples (3.6%) by FCM test. 75.8% (n = 47) of patients with PNH clone had aplastic anemia, 3.2% (n = 2) had Coombs (-) hemolytic anemia, 6.5% (n = 4) had unexplained cytopenia, 3.2% (n = 2) had MDS with refractory anemia, 1.6% (n = 1) had hemoglobinuria and 9.7% (n = 6) had others (elevated LDH, splenomegaly, etc.). In contrast, we detect no PNH clone test in patients who were screened for unexplained thrombosis. CONCLUSIONS: Our study showed that current clinical indications for PNH testing are highly efficient and diagnostic screening of suspected patients for PNH with FCM is recommended. However, advanced screening algorithms are required for patients presenting with unexplained thrombosis and normal complete blood count.

Therapeutic Plasma Exchange in Patients with Neurologic Disorders: Review of 63 Cases.

Therapeutic plasma exchange (TPE) is a procedure that reduces circulating autoantibodies of the patients. TPE is commonly used in neurological disorders where autoimmunity plays a major role. We report our experience with regard to the indications, adverse events and outcomes of plasma exchange in neurological disorders. Sixty-three patients were included to this retrospective study. Median age was 48 years (range 1-85), there was a predominance of males. Neurological indications included Guillain-Barrè syndrome (n = 22), myasthenia gravis (n = 21), chronic inflammatory demyelinating polyneuropathy (n = 7), polymyositis (n = 3), multifocal motor neuropathy (n = 2), acute disseminated encephalomyelitis (n = 2), neuromyelitis optica (n = 2), multiple sclerosis (n = 2), limbic encephalitis (n = 1) and transverse myelitis (n = 1). TPE was frontline therapy in 57 % of the patients (n = 36). Total number of TPE sessions was 517; median number of sessions per patient was 8 (range 1-66). TPE was done through a central venous access in 97 % and through a peripheral venous access in 3 % of the patients. Human albumin was used as replacement fluid in 49 %, hydroxyethyl starch (HES) in 49 % and fresh frozen plasma in 2 % of the cases. Adverse reactions were recorded in 60 % of the patients. Total ratio of complications in 517 TPE procedures was 10.8 % and these were mild and manageable such as allergic reactions and hypotension. Overall response rate was 81 %. Interestingly, complication and response rates were similar in both HES and human albumin groups. We conclude that TPE is an effective treatment in neurologic diseases in which autoimmunity plays an important role in the pathogenesis and HES can be used instead of albumin as replacement fluid in these disorders, since it is cost-effective, has similar efficacy and complication rates.

Quality of life, clinical effectiveness, and satisfaction in patients with beta thalassemia major and sickle cell anemia receiving deferasirox chelation therapy.

OBJECTIVES: There is a need to remove excess iron with iron chelation therapy (ICT) to avoid the serious clinical sequelae associated with iron overload in patients with beta thalassemia major (BTM) and sickle cell anemia (SCA). Due to the effects of the diseases and their treatments, ICT is still a major reason for unsatisfactory compliance. The aim of this single-center observational study was to evaluate the quality of life, clinical effectiveness, and satisfaction in pediatric and adult patients with BTM and SCA receiving deferasirox (DFX) chelation therapy. METHODS: In this study, 37 pediatric and 35 adult patients with BTM or SCA receiving DFX for at least 6 months participated. Upon receipt of Informed Consent Form, Case Report Form, Demographic Data Collection Form, Child Health Questionnaire-Parent Form, Life Quality Survey Short Form-36, and ICT Satisfaction Survey were used to obtain data for the effectiveness of ICT and parameters that may affect compliance to treatment and life quality of the participants. RESULTS: As a main index for the effectiveness of DFX chelation therapy, serum ferritin levels were higher than the normal values in the patients receiving DFX. The increased ferritin levels were also associated with hematological and biochemical abnormalities. Our findings regarding quality of life and satisfaction with DFX chelation therapy indicated that the patients with BTM or SCA had lower scores. Overall, problems with treatment regimen and side effects appeared to be common causes of poor compliance to DFX chelation therapy. CONCLUSIONS: Our findings suggest that health care providers should be aware of the importance of monitoring iron load with timely initiation of DFX chelation therapy and ongoing adjustments to chelation regimens and/or transfusion methods to decrease hospitalizations and improve compliance to ICT of the patients with BTM and SCA.

The Role of Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia: Results of a Retrospective Multicenter Study.

OBJECTIVE: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts. MATERIALS AND METHODS: In this retrospective multicenter study, 130 patients of ≥60 years old who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included. RESULTS: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment. Median overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of <2, increasing number of AZA cycles (≥5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact. CONCLUSION: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA.

Azacitidine versus decitabine in patients with refractory anemia with excess blast-Results of multicenter study.

The present study aimed to compare the efficacy and safety of azacitidine and decitabine in patients with myelodysplastic syndrome (MDS). A total of 88 patients diagnosed with refractory anemia with excess blast (RAEB) treated with azacitidine (n=57) or decitabine (n=31) were evaluated. Comparisons between azacitidine and decitabine groups were performed in the whole cohort, and in a 1:1 propensity score-matched cohort in order to reduce the simple selection bias. Patients who received azacitidine or decitabine had comparable overall response rates in both the unmatched (49.1% vs. 64.5%, p=0.166) and the propensity-matched cohorts (52% vs. 68%, p=0.248). The cumulative incidence of AML transformation at one year was comparable between azacitidine and decitabine in the unmatched (24.0% vs. 31.3%, p=0.26) and in the propensity-matched cohorts (18.7% vs. 31.5%, p=0.11). There was no difference in terms of transfusion requirement, febrile neutropenia episodes or the need for antifungal use during the treatment cycles in the propensity-matched cohort. The median overall survival was 20.4 months for azacitidine and 16.8 months for decitabine (p=0.59). Finally, we found that at least a four-cycle treatment with any HMA was a favorable factor. In conclusion, both azacitidine and decitabine have similar efficacy and toxicity profiles in the treatment of MDS-RAEB.

MicroRNA Expression Analysis in Patients with Primary Myelofibrosis, Polycythemia vera and Essential Thrombocythemia.

MicroRNAs (miRNA) are small non-coding RNA molecules that play critical roles in cell differentiation, proliferation and apoptosis and thus regulate haematopoietic stem cells and committed progenitor cells. We analyzed expressions of miRNAs associated with hematopoietic transformation of myeloid, erythroid and megakaryocytic progenitor cells during haematopoiesis (mir155, mir181a, mir221, mir222, mir223, mir451), in patients with primary myelofibrosis (PMF) (n = 22), polycythemia vera (PV) (n = 33), essential thrombocythemia (ET) (n = 49) and in healthy controls (n = 40) by quantitate/real time polymerase chain reaction. RT-PCR testing was negative for BCR-ABL1 fusion gene in all the patients. Mir155 was expressed in higher levels in all 3 disorders (p < 0.05). Mir221 was higher especially in ET and PMF group (p < 0.05). Mir222 expression was lower in PV patients (p < 0.05) and higher in ET and PMF patients compared to control group. Mir223 expression was higher in ET and PMF group than control group (p > 0.05). Mir451 levels were lower in all three groups compared to control group (p < 0.05). There was no difference in expression levels of mir181a between groups. JAK2V617F positivity, co-morbidities, drugs, and gender did not affect miRNA expressions. This study holds promise for the future application of these molecules for differential diagnosis and as therapeutic targets in Philadelphia chromosome negative myeloproliferative neoplasms.

Serum microRNAs; miR-30c-5p, miR-223-3p, miR-302c-3p and miR-17-5p could be used as novel non-invasive biomarkers for HCV-positive cirrhosis and hepatocellular carcinoma.

Recently, serum miRNAs have been evolved as possible biomarkers for different diseases including hepatocellular carcinoma and other types of cancers. Investigating certain serum miRNAs as novel non-invasive markers for early detection of HCV-positive cirrhosis and hepatocellular carcinoma (HCC). The expression profiles of 58 miRNA were analyzed in patient's plasma of chronic hepatitis C (CHC), HCV-positive cirrhosis and HCV-positive HCC and compared with control group samples. Totally 94 plasma samples; 64 patient plasma (26 CHC, 30 HCV-positive cirrhosis, 8 HCV-positive HCC) and 28 control group plasma, were included. The expression profiles of 58 miRNAs were detected for all patient and control group plasma samples by qRT-PCR using BioMarkTM 96.96 Dynamic Array (Fluidigm Corporation) system. In CHC group, expression profiles of miR-30a-5p, miR-30c-5p, miR-206 and miR-302c-3p were found significantly deregulated (p < 0.05) when compared versus control group. In HCV-positive cirrhosis group, expression profiles of miR-30c-5p, miR-223-3p, miR-302c-3p, miR-17-5p, miR-130a-3p, miR-93-5p, miR-302c-5p and miR-223-3p were found significantly deregulated (p < 0.05). In HCV-positive HCC group, expression profiles of miR-17-5p, miR-223-3p and miR-24-3p were found significant (p < 0.05). When all groups were compared versus control, miR-30c-5p, miR-223-3p, miR-302c-3p and miR-17-5p were found significantly deregulated for cirrhosis and HCC. These results imply that miR-30c-5p, miR-223-3p, miR-302c-3p and miR-17-5p could be used as novel non-invasive biomarkers of HCV-positive HCC in very early, even at cirrhosis stage of liver disease.

Profiles of serum microRNAs; miR-125b-5p and miR223-3p serve as novel biomarkers for HBV-positive hepatocellular carcinoma.

Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions including cancer. Certain microRNAs (miRNAs) have been shown early diagnostic potential for many types of cancer. The objective of this study was to investigate the potential of certain serum/plasma miRNAs as novel non-invasive biomarkers for early diagnosis of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). For this reason, the expression levels of 24 miRNA (let-7c, miR-92a-3p, 423-5p, 150-5p, 223-3p, 125b-5p, 342-3p, miR-206, 122-5p, 375, 223-5p, 10a-5p, 23b-5p, 99a-5p, 23a-5p, 10a-3p, 122-3p, 125b-1-3p, 23b-3p, 125b-2-3p, 23a-3p, 92a-1-5p, 92a-2-5p, 99a-3p) were analyzed in plasma of patients with chronic hepatitis B, HBV-positive cirrhosis and HBV-positive HCC and compared with control group samples. Totally 94 plasma samples; 28 control and 66 patient plasma (24 CHB, 22 HBV-positive cirrhosis, 20 HBV-positive HCC) and were included in this study. The expression levels of 24 miRNAs were detected for all control and patient group plasma samples by qRT-PCR using BioMark™ 96.96 Dynamic Array (Fluidigm Corporation) system. The expression levels of miR-125b-5p were detected 2.85 fold, 2.46 fold and 1.89 fold (p = 0.01513, p = 0.0009440, p = 0.0001446) up regulated in CHB, HBV-positive cirrhosis and HBV-positive HCC, respectively when compared versus control group individually by Mann-Whitney U test. The expression levels of miR-223-3p were detected 5.55 fold, 13.88 fold and 12.65 fold (p = 0.01513, p = 0.0009440, p = 0.0001446) down regulated in same comparisons. When all groups were compared versus control group by one-way ANOVA test, the expression levels of miR-223-3p were also found statistically significant (p < 0.05). Although not statistically significant, miR-125b-5p tended to be upregulated. (p = 0.07192). These results significantly imply that miR-125b-5p and miR223-3p could be used as novel non-invasive biomarkers of HBV-positive HCC in very early, even at CHB stage of liver disease.

Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura: a retrospective multicenter study.

UNLABELLED: Thrombotic thrombocytopenic purpura (TTP) is a particular form of thrombotic microangiopathy typically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological abnormalities, and renal dysfunction. TTP requires a rapid diagnosis and an adapted management in emergency. Daily sessions of therapeutic plasma exchange (TPE) remain the basis of management of TTP. Also, TTP is a rare disease that is fatal if it is not treated. TPE has resulted in excellent remission and survival rates in TTP patients. AIM: We aimed to present our experience in 163 patients with TTP treated with TPE during the past 5years from 10 centers of Turkey. PATIENTS AND METHODS: One hundered and sixty-three patients with TTP treated with TPE during the past 5years from 10 centers of Turkey were retrospectively evaluated. TPE was carried out 1-1.5times plasma volume. Fresh frozen plasma (FFP) was used as the replacement fluid. TPE was performed daily until normalization of serum lactate dehydrogenase (LDH) and recovery of the platelet count to >150×10(9)/dL. TPE was then slowly tapered. Clinical data, the number of TPE, other given therapy modalities, treatment outcomes, and TPE complications were recorded. RESULTS: Fifty-eight percent (95/163) of the patients were females. The median age of the patients was 42years (range; 16-82). The median age of male patients was significantly higher than female (53 vs. 34years; p<0.001). All patients had thrombocytopenia and microangiopathic hemolytic anemia. At the same time, 82.8% (135/163) of patients had neurological abnormalities, 78.5% (128/163) of patients had renal dysfunction, and 89% (145/163) of patients had fever. Also, 10.4% (17/163) of patients had three of the five criteria, 10.4% (17/163) of patients had four of the five criteria, and 6.1% (10/163) of patients had all of the five criteria. Primary TTP comprised of 85.9% (140/163) of the patients and secondary TTP comprised of 14.1% (23/163) of the patients. Malignancy was the most common cause in secondary TTP. The median number of TPE was 13 (range; 1-80). The number of TPE was significantly higher in complete response (CR) patients (median 15.0 vs. 3.5; p<0.001). CR was achieved in 85.3% (139/163) of the patients. Similar results were achieved with TPE in both primary and secondary TTP (85% vs. 87%, respectively; p=0.806). There was no advantage of TPE+prednisolone compared to TPE alone in terms of CR rates (82.1% vs. 76.7%; p=0.746). CR was not achieved in 14.7% (24/163) of the patients and these patients died of TTP related causes. There were no statistical differences in terms of mortality rate between patients with secondary and primary TTP [15% (21/140) vs. 13% (3/23); p=0.806]. But, we obtained significant statistical differences in terms of mortality rate between patients on TPE alone and TPE+prednisolone [14% (12/86) vs. 3% (2/67), p<0.001]. CONCLUSIONS: TPE is an effective treatment for TTP and is associated with high CR rate in both primary and secondary TTP. Thrombocytopenia together with microangiopathic hemolytic anemia is mandatory for the diagnosis of TTP and if these two criteria met in a patient, TPE should be performed immediately.