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Objective/background: Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. Methods: This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. Results: Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III–IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667–199.255; p =

Adult patients with sickle cell disease (SCD) are highly susceptible to stem cell transplant complications, including drug toxicity, graft versus host disease (GVHD), and graft rejection due to SCD-related tissue damage, endothelial activation, and inflammation. The scarcity of compatible stem cells for transplantation further limits treatment options, with only 43 cases of adult allogeneic peripheral blood stem cell transplantation (allo-PSCT) from human leukocyte antigen (HLA)-identical sibling donors reported in the international registry for the period 1986-2013. Herein we report remarkable outcomes in a cohort of adult SCD patients who underwent allo-PSCT using a fludarabine (Flu), busulfan (Bu), and anti-T-cell lymphocyte globulin (ATG)-based conditioning regimen in combination with very low dose total body irradiation (TBI), followed by post-transplant cyclophosphamide (Cy) and sirolimus as GVHD prophylaxis. We performed a single-center, retrospective study consisting of 20 consecutive patients (mean age 33.4 years) who underwent allo-PSCT from HLA-matched related donors with a conditioning regimen of Flu 150/Bu 3.2/Cy 29/ATG 30 (Fresenius)/TBI 200 between September 2013 and September 2017. Data were validated by an independent data audit group of the affiliated JACIE-accredited transplantation center. All patients experienced a sustained donor cell engraftment. Full donor chimerism (total cell) occurred within 180 days in all patients. Mean duration of follow-up was 13.8 months (range: 0.3-50 months), with 12 (60%) patients completing 12 months. No non-relapse mortality or graft rejection occurred. Successful treatment was achieved without the presence of graft loss, grade III-IV acute GVHD, extensive chronic GVHD, or other major complications. Allo-PSCT in combination with Flu 150/Bu 3.2/Cy 29/ATG 30(Fresenius)/TBI 200- Cy/Sirolimus therapy yielded encouraging outcomes with no mortality and low incidence of GVHD. Further controlled studies will be necessary to compare transplant protocols and long-term outcomes.

Background Chronic myeloid leukemia (CML) is a disease resulting from BCR-ABL gene fusion. It is possible to monitor treatment by molecular testing for BCR-ABL. The lymphocyte-to-monocyte ratio (LMR) is a commonly used marker associated with prognosis in various neoplasms. This study was performed to evaluate the relevance of absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR in predicting molecular response status in patients with chronic phase CML. Methods Samples submitted to our hematology laboratory for BCR-ABL testing between April 2012 and October 2018 were retrospectively reviewed. Concurrent hemogram testing together with the results of quantitative reverse transcriptase-polymerase chain reaction were noted. Data were grouped according to molecular response status and the ALC, AMC, and LMR were compared among patient groups. Results A total of 224 samples from 95 patients were included in the study. Analysis revealed differences between groups when newly diagnosed patients were compared with patients undergoing treatment, regardless of response status. However, analyzing the groups according to molecular response status failed to reveal differences in ALC, AMC, or LMR. Conclusions ALC, AMC, and LMR are not potential biomarkers for predicting molecular response status in patients with chronic phase CML.

Background The profile of leukocytes in bronchoalveolar lavage (BAL) fluid provides important information for diagnosing various lung diseases. A differential cell count of BAL is conventionally performed by evaluating centrifuged samples under a light microscope and enumerating the stained cells. Another rarely used method to identify BAL leukocytes is flow cytometry (FCM). However, there are no guidelines for standardizing this method and related literature is limited. This study aimed to evaluate the accuracy of FCM for identifying BAL leukocytes. Methods The BAL samples accepted to the hematology laboratory between 2014 - 2018 were retrospectively evaluated via light microscopy (LM) by a hematologist; while flow cytometric analyses with a monoclonal antibody panel composed of CD45/CD14/CD16 were noted by another doctor. The percentages of macrophages, lymphocytes, neutrophils and eosinophils determined by both methods were recorded for analysis. Correlations between the results from LM and FCM were investigated. In addition, compatibility between LM and FCM for denoting pathological values for each cell type was checked. Results Among 140 reviewed BAL samples, 76 were included for further analysis. Comparisons revealed strong correlations between FCM and LM for identifying macrophages, lymphocytes, neutrophils, and eosinophils. In addition, regarding the normal cutoff values for each leukocyte type, FCM and LM were similar in the identification of pathological changes of all cell types except eosinophils. Conclusions Flow cytometry was found to be feasible for use instead of LM and might become a more widely used technique to analyze BAL fluid in the future.

Obtaining informed consent from hematopoietic stem cell recipients and donors is a critical step in the transplantation process. Anxiety may affect their understanding of the provided information. However, use of audiovisual methods may facilitate understanding. In this prospective randomized study, we investigated the effectiveness of using an audiovisual method of providing information to patients and donors in combination with the standard model.A 10-min informational animation was prepared for this purpose. In total, 82 participants were randomly assigned to two groups: group 1 received the additional audiovisual information and group 2 received standard information. A 20-item questionnaire was administered to participants at the end of the informational session.A reliability test and factor analysis showed that the questionnaire was reliable and valid. For all participants, the mean overall satisfaction score was 184.8±19.8 (maximum possible score of 200). However, for satisfaction with information about written informed consent, group 1 scored significantly higher than group 2 (p=0.039). Satisfaction level was not affected by age, education level, or differences between the physicians conducting the informative session.This study shows that using audiovisual tools may contribute to a better understanding of the informed consent procedure and potential risks of stem cell transplantation.Amaç: Hematopoietik kök hücre alıcıları ve donörlerden bilgilendirilmiş onam alınması, nakil sürecinin en önemli basamağıdır. Görsel yöntemlerden yararlanılması anlamayı kolaylaştırabilir. Bu prospektif randomize çalışmada sözel ve yazılı bilgilendirmeye ilave olarak audiovizüel yöntem kullanılmasının standart yönteme göre etkinliğinin araştırılması amaçlanmıştır. Gereç ve Yöntemler: On dakikalık kısa bir bilgilendirme animasyonu hazırlatıldı. Toplam 82 katılımcı rastgele 2 gruba ayrıldı: Grup 1 (görsel bilgilendirme yönteminin ilave edildiği grup) ve grup 2 (standart yöntem uygulanan grup). Bilgilendirme işlemi sonunda katılımcılara 20 soruluk bir anket uygulandı. Ayrıca, yeni yöntemin sonuçlarının kişiler arası farklılıktan etkilenip etkilenmediği test edildi. Bulgular: Güvenirlik testi ve faktör analizi anketin güvenilir ve geçerli olduğunu gösterdi. Tüm olgular için genel memnuniyet ortalama değeri 200 üzerinden 184,8±19,8 olarak bulundu. Yazılı bilgilendirilmiş onam form memnuniyeti ortalama puanları yönünden grup 1’deki olguların memnuniyetleri grup 2’ye oranla anlamlı olarak daha yüksek olduğu saptandı (p=0,039). Sözel olarak bilgi veren doktor ve bilgilendirme animasyonu memnuniyeti bakımından gruplar arasında fark saptanmadı. Olguların memnuniyet seviyesi yaş, eğitim durumu ve bilgilendiren kişiler arası farklılıktan etkilenmedi. Sonuç: Bu çalışma, görsel yöntemlerin kullanılmasının işlem ve muhtemel risklerinin daha iyi anlaşılmasına katkı sağlayabileceğini göstermektedir. Anahtar Sözcükler: Hematopoietik kök hücre, Donör, Bilgilendirilmiş onam, Audovizuel yöntem, Kemik iliği nakli.

Today, voluntary donation of peripheral blood stem cells by healthy donors for allogeneic hemopoietic cell transplantation is common worldwide. Such donations are associated with small but measurable risks of morbidity and mortality. Most complications are associated with citrate infusion during cell collection. We studied the effects of citrate infusion on the QTc and other vital parameters during and after peripheral stem cell apheresis in volunteers.To ensure that donors were healthy, screening included taking a detailed medical history, physical examination, and laboratory measurements of plasma calcium and magnesium. Corrected QT (QTc) values were assessed using a 12-lead electrocardiographic platform that derived QTc values automatically.In all, 141 apheresis procedures were performed. The mean QTc values at baseline, at 2 and 4 h during the procedure, and at 30 min after the procedure, were 347.6 ± 59.5, 349.9 ± 52.8, 391.8 ± 54.0, and 404.8 ± 59.2 ms, respectively. The baseline and 2 h QTcs did not differ significantly, but the baseline QTc did differ significantly from the 4 h and 30 min after the procedure values. The plasma levels of calcium and magnesium did not significantly differ before and after the procedure.QTc prolongation may develop during leukopheresis, particularly if the procedure takes more than 2 h. Thus, to enhance donor safety, QTc measurement should be standard for all donors. In addition, any family history of sudden death should be noted, to prevent the development of possible fatal arrhythmia in susceptible donors.

PubMedID: 27068408 Sickle cell disease (SCD), one of the most common genetic disorders worldwide, is characterized by hemolytic anemia and tissue damage from the rigid red blood cells. Although hydroxyurea and transfusion therapy are administered to treat the accompanying tissue injury, whether either one prolongs the lifespan of patients with SCD is unknown. SCD-related mortality data are available, but there are few studies on mortality-related factors based on evaluations of surviving patients. In addition, ethnic variability in patient registries has complicated detailed analyses. The aim of this study was to investigate mortality and mortality-related factors among an ethnically homogeneous population of patients with SCD. The 735 patients (102 children and 633 adults) included in this retrospective cohort study were of Eti-Turk origin and selected from 1367 patients seen at 5 regional hospitals. A central population management system was used to control for records of patient mortality. Data reliability was checked by a data supervision group. Mortality-related factors and predictors were identified in univariate and multivariate analyses using a Cox regression model with stepwise forward selection. The study group included patients with homozygous hemoglobin S (Hgb S) disease (67 %), Hb S-ß0 thalassemia (17 %), Hgb S-ß+ thalassemia (15 %), and Hb S-? thalassemia (1 %). They were followed for a median of 66 ± 44 (3–148) months. Overall mortality at 5 years was 6.1 %. Of the 45 patients who died, 44 (6 %) were adults and 1 (0.1 %) was a child. The mean age at death was 34.1 ± 10 (18–54) years for males, 40.1 ± 15 (17–64) years for females, and 36.6 ± 13 (17–64) years overall. Hydroxyurea was found to have a notable positive effect on mortality (p = 0.009). Mortality was also significantly related to hypertension and renal damage in a univariate analysis (p = 0.015 and p = 0.000, respectively). Acute chest syndrome, splenic sequestration, and prolonged painful-crisis-related multiorgan failure were the most common causes of mortality. In a multivariate analysis of laboratory values, only an elevated white blood cell count was related to mortality (p = 0.009). These data show that despite recent progress in the treatment of SCD, disease-related factors continue to result in mortality in young adult patients. Our results highlight the importance of evaluating curative treatment options for patients who have an appropriate stem cell donor in addition to improving patient care and patient education. © 2016, Springer-Verlag Berlin Heidelberg.

We sought to use computed tomography (CT) data to support the correct differential diagnosis of patients with spontaneous intramural hematomas of the gastrointestinal tract, to aid in the clinical management of those using oral anticoagulants.Patient data were retrospectively analyzed and patients were divided into two groups. The first group contained 10 patients (5 females, 5 males, median age 65 years [range 35-79 years]) who had been diagnosed with spontaneous intramural hematomas of the gastrointestinal tract. The second group contained nine patients (5 females, 4 males, median age 41 years [range 24-56 years]) who exhibited intestinal wall thickening on CT, and who had been diagnosed with ulcerative colitis, Crohn's disease, ameboma, and lymphoma. The enhancement patterns in the CT images of the two groups were compared by an experienced and inexperienced radiologist. The differences in values were subjected to ROC analysis.Inter-observer variability was excellent (0.84) when post-contrast CT images were evaluated, as were the subtraction values (0.89). The subtracted values differed significantly between the two groups (p=0.0001). A cutoff of +31.5 HU was optimal in determining whether a hematoma was or was not present.Contrast enhancement of an intestinal wall hematoma is less than that of other intestinal wall pathologies associated with increased wall thickness. If the post-contrast enhancement of a thickened intestinal wall is less than +31.5 HU, a wall hematoma is possible.

Sparse data are available about the effects of apheretic graft composition on the clinical transplant outcome in allotransplanted patients who have hematologic malignant disease. Major obstacles in recent studies have included heterogeneity of patient populations and differences in the conditioning regimens used.This prospective study included 50 patients who had acute myeloblastic leukemia and received busulfan-fludarabine-antithymocyte globulin-based conditioning for peripheral allogeneic stem cell transplant. The concentration of CD34+ cells, T-cell subsets, B cells, and natural killer cells in the graft were analyzed by flow cytometry in the donors who were matched for human leukocyte antigen.In univariate analysis, infusion with a higher dose of natural killer cells (1.55 × 106/kg) was associated with improved survival (P = .007 for disease-free survival; P = .024 for overall survival) in patients with acute myeloblastic leukemia. Cox regression models revealed that increased concentration of natural killer cells and CD34+ cells positively affected the clinical outcome of allotransplanted patients (P = .005 for both cell types). According to univariate analysis, these findings were dependent on minimal residual disease and acute graft-versus-host disease. Graft-versus-host disease (acute and chronic forms) was not affected by graft composition.Our results suggest that increased concentration of natural killer cells and CD34+ cells in the apheretic product may predict better survival. In contrast, busulfan-fludarabine-antithymocyte globulin-based conditioning eliminates the disadvantages that resulted from the high content of T-cell subsets and B cells, and the course of the transplant and clinical parameters were not affected by the amount of T and B cells.

OBJECTIVES Endothelium is the major tissue for hyperacute and acute rejection. Binding of antibody to endothelium activates several immunologic mechanisms. Antiendothelial cell antibodies are a group of nonhuman leukocyte antigen antibodies that may play a role in the induction of an immunologic reaction that triggers inflammation. The aim of this study was to investigate whether there was an association between antiendothelial cell antibody positivity and panel reactive antibody positivity in renal transplant patients. MATERIALS AND METHODS In this study, we investigated the association between antiendothelial cell antibodies and panel reactive antibody Class I class II crossmatch positivity in patients, and compared these results with results from 100 healthy volunteers. All serum samples were analyzed by bead-based technology for calculated panel reactive antibody positivity; in addition, slides were used, each containing human umbilical vein endothelial cells and capillary-rich tissue for antiendothelial cell antibody positivity. RESULTS Antiendothelial cell antibodies was positive in 48 of 89 patients (panel reactive antibody Class I class II negative), 22 of 35 patients (class I-positive), 25 of 39 patients (class II-positive), 26 of 40 (class I class II positive), and 37 of 57 serologic and flow cytometry crossmatch-positive patients (P ≤ .016), and ultimately, in 122 of 205 patients and 25 of 100 volunteers (P ≤ .001). Antiendothelial cell antibody positivity was more frequent in panel reactive antibody-positive than negative patients and the control group. CONCLUSIONS Binding of antiendothelial cell antibodies to endothelial cells may activate complement by the classical pathway and cause upregulation of adhesion molecules. This study questioned the antigenic specificity of antiendothelial cell antibodies. Our study results showed that antiendothelial cell antibodies may play an important role for graft destruction, independent of panel reactive antibody and crossmatch positivity.

The purpose of this study is to determine whether hyperthermia-induced hyperventilation with subsequent hypocapnia is relevant to febrile seizures in children. This is only the second study to measure pCO2 and pH values in children with febrile seizures. This prospective case-control study enrolled 18 children who presented with febrile seizures and 18 children who presented with a febrile illness without seizures. Venous blood gas analyses were measured both from the febrile seizure and control group. There was no significant difference in mean blood pH between the febrile seizure and control groups but blood pCO2 was significantly lower in the febrile seizure group. Patients with complex febrile seizures exhibited significantly lower pCO2 levels within 1 hour of seizure onset than patients with simplex febrile seizures. These data indicate that febrile seizures may be associated with hyperventilation and that the ensuing hypocapnia may contribute to the development of febrile seizures.

Handan Canan,1 Selçuk Sizmaz,2 Rana Altan-Yaycioğlu,1 Çağla Saritürk,3 Gürsel Yilmaz41Department of Ophthalmology, Adana Teaching and Medical Research Center, Baskent University School of Medicine, 2Department of Ophthalmology, Çukurova University School of Medicine, 3Department of Biostatistics, Adana Teaching and Medical Research Center, Baskent University School of Medicine, 4Department of Ophthalmology, Baskent University School of Medicine, Ankara, TurkeyPurpose: To describe 1-year clinical results of intravitreal ranibizumab treatment in patients with choroidal neovascularization secondary to exudative age-related macular degeneration (AMD) and to evaluate whether early treatment is a predictive value for prognosis of the disease.Materials and methods: Clinical records were retrospectively reviewed of 104 eyes that underwent intravitreal ranibizumab therapy for exudative AMD. Patients were divided into two groups according to their symptom duration: group 1

To compare the success and complication rates of ultrasound-guided or palpation-guided punctures of the common femoral artery in a prospective randomized study.Percutaneous femoral arterial access is sometimes difficult to perform and is the source of complications. It has not been established whether ultrasound-guided puncture of the common femoral artery is the standard practice for angiography.Two hundred and eight patients were randomized into two groups. One had ultrasound-guided puncture and the other had palpation-guided puncture of the common femoral artery. The technical success, first pass success rate, total number of attempts required for access, time to sheath insertion, pain during puncture, and access-related complication were compared.Technical success tended to be higher and the complication rates tended to be lower in the ultrasound-guided group but the difference did not reach statistical significance (P = 0.052 and P = 0.052). The first pass success rate was higher, total number of attempts required for access and time to sheath insertion were lower in the ultrasound-guided group. Atheromatous plaques on the common femoral artery, iliac artery obstructive lesion, previous ipsilateral puncture of the common femoral artery, obesity, and blood pressure during puncture did not change the outcome.Ultrasound guidance improves secondary outcomes of the common femoral artery puncture when compared to palpation-guided puncture. Technical success and complication rates seem lower in the presence of ultrasound guidance but larger study populations are needed to verify the result.

Introduction Glucagon-like peptide-1 (GLP-1) originates from the gastrointestinal system in response to the presence of nutrition in the intestinal lumen and potentiates postprandial insulin secretion. Also, it acts as an immune-modulator which has influences on cell-mediated immunity. The aim of this study was to determine the impact of early enteral nutrition versus late enteral nutrition on plasma GLP-1 levels and the relationship between GLP-1 changes and cell-mediated immunity. Materials and methods The study was designed as a prospective, single-blinded study and carried out in the neurology intensive care unit (ICU) of a university hospital. Twenty-four naive patients with acute thromboembolic cerebrovascular events, with National Institute of Health (NIH) stroke scores between 12 and 16, were included. Any condition interfering with GLP-1 and immunity was regarded as exclusion criterion. Two patients died, and two dropped out of the study due to complicating conditions. Patients were randomly subjected to early enteral feeding within the first 24 hours (Group 1), or late enteral feeding, beginning 48 hours after admission (Group 2) via a nasogastric tube. Calculated daily energy requirement was supplemented with parenteral nutrition, starting on the first study day for both groups. Blood samples were obtained before, and at 5, 15, 30, 60 and 120 minutes after the first enteral feeding for GLP-1 assays; this procedure was repeated on the third day. Before and 24 hours after the first enteral feeding, samples were also taken for immunological analysis. Clinical observations were recorded. Pre- and post-feeding plasma GLP-1 changes between the two groups and within groups were evaluated. Lymphocyte subgroup changes before and 24 hours after the first enteral feeding in relation to GLP-1 changes were sought as well. Results Group 1 and Group 2 exhibited similar GLP-1 levels in the pre-feeding and post-feeding periods for both the first time and the third day of enteral feeding. Also, no significant change in pre-/post-feeding GLP-1 levels was observed within groups. T-helper and T-regulatory cells increased, T-cytotoxic cells decreased significantly in Group 1 (P = 0.02; P = 0.036; P = 0.0019), but remained the same in Group 2 after enteral feeding. Positive but statistically insignificant clinical effects in terms of predisposition to infections (10% vs 40%) and median time of ICU stay (10 vs 15 days) were observed in Group 1. Conclusions Depending on our findings, we propose that early enteral feeding may cause amelioration in cell-mediated immunity via factors other than GLP-1 in ICU patients with acute thromboembolic stroke. However, the possible deleterious effects of parenteral nutrition cannot be ruled out.