The frequency of synovitis and calcium pyrophosphate deposition with ultrasound is increased in transfusion-dependent beta-thalassaemia patients: effect of iron accumulation?

OBJECTIVES: To determine the frequency of synovitis and calcium pyrophosphate deposition (CPDD) with ultrasound (US) in the wrists of transfusion dependant (TD) beta-thalassaemia patients and to investigate the associated factors with these pathologies. METHODS: Eighty-seven beta-thalassaemia patients (46 thalassaemia major and 41 thalassaemia minor patients) were grouped into two as TD and transfusion non-dependent (TND)-thalassaemia patients. Under bilateral wrist US the presence of synovial hypertrophy (SH), power Doppler signal (PD) combined synovitis (SH+PD), tenosynovitis, and triangular fibrocartilage complex (TFC)-cartilage calcification (CC) were examined. SH, PD, and combined synovitis in the US were classified as Grade-0 (no), Grade-1 (minimal), Grade-2 (moderate), and Grade-3 (severe). RESULTS: The incidence of moderate/severe SH, PD, and combined synovitis with US was 34.8%, 17.4%, and 34.8% in TD-thalassaemia patients, respectively, but none in TND patients (p<0.001, p=0.006, p<0.001). The frequency of TFC-CC with US was 32.6% in TD and 2.4% in TND-thalassaemia patients (p<0.001). Ferritin level was positively correlated with SH (r=0.414, p<0.001), PD (r=0.279, p=0.009) and combined synovitis scores (r=0.402, p<0.001). Ferritin level (OR:1.001, CI:1.000-1.002) and the presence of TFC-CC (OR:25.048, CI:5.187-120.951) were determined as to be associated with moderate/severe combined synovitis. CONCLUSIONS: The presence of synovitis and TFC-CC with the US is common in patients with beta-thalassaemia who have had recurrent blood transfusions. Iron overload in beta-thalassaemia patients may cause CPDD and synovial inflammation.

Mean Platelet Volume and Mean Platelet Volume/Platelet Count Ratio Are Predictors of Late-Onset Sepsis in Preterm Infants: A Case-Control Study.

Objective: Our aim was to assess mean platelet volume (MPV) and mean platelet volume to platelet count ratio (MPR) in the setting of late-onset sepsis (LOS) and their association with the type of bacteria causing LOS. Study design: The MPV and MPR levels were obtained at the onset of LOS and then assessed in intra/inter group analyses in preterm infants. Results: Overall, 136 preterm infants were enrolled. The MPV and MPR levels were higher during a LOS event (P < 0.001). A MPV cutoff of >9.2 was related with a sensitivity of 63% and a specificity of 73% for predicting LOS (P < 0.001). A MPR cutoff of >0.15 was related with a sensitivity of 88% and a specificity of 63% for predicting gram negative LOS (P < 0.001). Conclusion: Elevated MPV values and MPR ratios may be helpful in assessing LOS.

Red Cell Distribution Width to Platelet Count Ratio Reference Intervals in Premature Infants Beyond the First Week of Life.

Objective: Red cell distribution width (RDW) is a parameter of complete blood count (CBC). The RDW to platelet count ratio (RPR) is a new index that has been shown to reflect the severity of inflammation. We aim to determine the reference interval (RI) of RPR for premature newborns. Study design: The medical records of preterm infants who were followed up between January 2016 and December 2018 were reviewed. CBC levels were measured in 144 infants at <72 hours of age. Results: CBCs of infants (gestational age from 28 to 35weeks) had a RI of 0.038-0.126 for the RPR. The RI for RPR in infants with a gestational age of 32-35weeks was 0.042-0.129; and the RI for infants at 28-31weeks was 0.022-0.121. Conclusion: Establishment of RI for RPR in premature infants will allow clinical correlation of RPR alterations in this population.

Effectiveness of kinesiologic taping on function and pain in patients with hemophilia A.

Background: Hemophilic arthropathy frequently results in musculoskeletal adjustments that impair functional capacity. Aim: We investigated the effects of kinesiologic taping on patients with hemophilic arthropathy in this study. Materials and Methods: Twenty-six patients were enrolled. Thirteen patients formed the Kinesiologic taping group (KT) and received the interventional protocol consisting of three kinesiologic taping sessions during three weeks; and 13 patients formed the control group (CG) and made three weeks of home exercises. All patients were evaluated using the Functional Independence Score in Hemophilia (FISH), Hemophilia Joint Health Score (HJHS), and Visual Analog Scale (VAS) at baseline, one week, and three weeks. Results: The mean scores for the VAS, HJSS, and FISH differed significantly before and after 3 weeks in both groups (P < 0.001). However, the differences in medians after the treatment were significantly greater in the KT group than in the CG group (P < 0.001). Conclusions: Kinesiologic taping was associated with physical improvement in hemophilia patients; however, also kinesiologic taping led to significant improvement in VAS scores.

Evaluation of thiol/disulfide hemostasis and serum Ischemia modified albumin as oxidative stress biomarkers in systemic lupus erythematosus patients: Relationship with major organ involvement and disease activity.

OBJECTIVES: We aimed to compare thiol/disulfide hemostasis and serum ischemia-modified albumin (IMA) levels, which are indicators of oxidative stress (OS), in patients with systemic lupus erythematosus (SLE), with the healthy control (HC) group and to evaluate the relationship of these parameters with disease activity and major organ involvement. MATERIAL-METHODS: Eighty-four SLE patients and 96 HCs were included in this study. The disease activity of SLE patients was calculated using The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Patients with SLEDAI-2K ≤ 5 were classified as low disease activity (LDA) and those with SLEDAI-2K > 6 as high disease activity (HDA). Thiol/disulfide hemostasis was evaluated using a new automated method and natural thiol (NT), total thiol (TT), disulfide (SS) levels, SS/NT, SS/TT, NT/TT ratios, and serum IMA levels were recorded. RESULTS: NT and TT levels were significantly lower (490.11 ± 123.61 vs 536.96 ± 86.05, p = 0.003) (532.56 ± 125.80 vs 565.72 ± 89.82, p = 0.046), SS level (21.22 ± 11.75 vs 13.37 ± 9.31, p < 0.001) was higher, and SS/TT (4.64 ± 2.93 vs 2.52 ± 1.82, p < 0.001) and SS/NT (4.12 ± 2.33 vs 2.35 ± 1.59, p < 0.001) ratios were significantly higher in SLE patients compared to HCs. IMA values were not different between the two groups (p = 0.920). NT (449.84 ± 136.98 vs 520.32 ± 104.11, p = 0.012) and TT levels (492.01 ± 138.45±562.97 ± 107.09, p = 0.013) were significantly lower and serum IMA levels (0.802 ± 0.089 vs 0.764 ± 0.040, p = 0.023) were significantly higher in SLE patients with HDA than in LDA patients. There was a weak negative correlation between NT (r = -0.284, p=0.009) (r = -0.291, p = 0.007) and TT levels (r = -0.281, p = 0.010) (r = -0.289, p = 0.008) and a weak positive correlation between IMA levels (r = 0.279, p = 0.011) (r = 0.263, p = 0.016) and SLEDAI-2K, and major organ involvement. CONCLUSION: It is thought that thiol/disulfide hemostasis and IMA levels may be used as ideal biomarkers of OS in SLE patients and may reflect the disease activity and major organ involvement.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

Effects of iron deficiency anemia on peripapillary and macular vessel density determined using optical coherence tomography angiography on children.

PURPOSE: To evaluate retinal vascular parameters by optical coherence tomography angiography (OCT-A) in iron deficiency anemia (IDA). METHODS: Thirty-two patients with IDA (study group) and 30 healthy children (control group) were enrolled in the study. All subjects underwent a complete ocular examination. OCT-A scans were performed in a 6 × 6 mm area centered on the macula. Foveal avascular zone (FAZ), non-flow area (NFA), FAZ perimeter (PERIM), acircularity index (AI) of FAZ, and foveal density (FD) were measured in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). SCP and DCP were also scanned centered on the optic disk. Hemoglobin (Hb), mean corpuscular volume (MCV), serum iron, total iron-binding capacity (TIBC), and ferritin were also studied and compared for both groups. RESULTS: The mean age was 12.22 ± 4.48 years (ranged 5-18 years) in the study group and 12.37 ± 3.76 years (ranged 6-18 years) in the control group. The mean FAZ value was 0.290 ± 0.09 mm2 in the study group and 0.298 ± 0.11 mm2 in the control group. The mean NFA value was 0.477 ± 0.10 mm2 in the study group and 0.486 ± 0.13 mm2 in the control group (p > 0.05). FD and AI were not statistically significant between the study group and control group (p > 0.05). The mean value for SCP was statistically significant between the study group and control group (p < 0.05). The mean value for DCP was not significantly different between the study and control groups (p > 0.05). The mean values for capillary density on optic disk were also statistically significant between the study group and control group (p < 0.05). A negative correlation was found between serum iron, TIBC, and capillary plexus density (p < 0.05). A positive correlation was found between MCV and ferritin values and capillary plexus density (p < 0.05). CONCLUSION: IDA had significantly lower capillary plexus density. We detected retinal microvascular changes in young IDA patients before significant ocular anomalies, especially ischemic changes, developed.

Deferasirox in children with transfusion-dependent thalassemia or sickle cell anemia: A large cohort real-life experience from Turkey (REACH-THEM).

OBJECTIVES: To evaluate the long-term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion-dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey. METHODS: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin [SF] level >1000 µg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice. RESULTS: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 µg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 µg/L), SCA (1655.5 to 1260 µg/L), and across age groups of 2-6 years (1971.5 to 1499 µg/L), 7-12 years (1688.5 to 1159.8 µg/L), and 13-18 years (1496.5 to 1107 µg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, -579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range. CONCLUSIONS: Deferasirox has long-term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance.

Useful Platelet Indices for the Diagnosis and Follow-Up of Patent Ductus Arteriosus.

OBJECTIVE: The aim of this study was to assess the utility of early postnatal platelet indices in the prediction of hemodynamically significant patent ductus arteriosus (hsPDA) and its response to pharmacological treatment in preterm infants. STUDY DESIGN: The medical records of 971 infants with gestational age < 30 weeks and birth weight < 1,500 g were analyzed retrospectively. Infants with hsPDA comprised the study group and those without hsPDA comprised the control group. Complete blood count results were recorded, and red cell distribution width-to-platelet ratio (RPR) and platelet mass were calculated. RESULTS: A total of 481 infants, 169 in the hsPDA group and 312 in the control group, were included. In terms of platelet indices, the hsPDA group showed significantly lower mean platelet volume (MPV) and platelet mass, whereas RPR was significantly higher (p < 0.05, respectively). Multiple logistic regression analysis showed that RDS (relative ratio [RR]: 2.39; 95% confidence interval [CI]: 1.45-3.93; p < 0.001), MPV < 7.85 (RR: 3.71; 95% CI: 2.29-6.01; p < 0.001), and RPR > 0.070 (RR: 5.33; 95% CI: 3.28-8.65; p < 0.001) were independent risk factors for hsPDA. CONCLUSION: Low MPV and platelet mass and high RPR in the first hours of life are risk factors for hsPDA and hsPDA refractive to pharmacological treatment with ibuprofen in preterm infants.

Increased vitamin B12 levels in children with zinc deficiency.

Additional nutritional deficiencies may accompany zinc deficiency. We determined the vitamin B12 levels in patients with zinc (Zn) deficiency. This retrospective study enrolled 256 patients age 6 months to 16 years (176 females and 80 males) in whom Zn levels in hair samples were measured concurrently with serum vitamin B12 and ferritin levels. For all patients, we retrospectively assessed the hair Zn levels, serum ferritin and vitamin B12 levels, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution levels. Data were analyzed to determine whether there was a significant difference between any of these parameters and the presence of vitamin B12 deficiency between patients with and without Zn deficiency. In all 118 patients had Zn levels < 100 µg/g and 138 patients had levels > 100 µg/g. No significant differences were observed in ferritin levels, red blood cell parameters, or presence of iron deficiency or anemia between the two groups (p > 0.05). The median vitamin B12 level was 323 (range 238-440) pg/mL in the Zn-deficient group and 276 (range 208-382) pg/mL in those with normal Zn levels. Vitamin B12 levels were significantly higher in the Zn-deficient group (p = 0.02). A significant negative correlation was detected between vitamin B12 levels and Zn levels (r = -0.17, p = 0.004). Vitamin B12 levels are higher in patients with Zn deficiency; thus, Zn may have a negative effect on vitamin B12 levels.

Central nervous system complications during treatment in childhood acute leukemia.

OBJECTIVE: Central nervous system (CNS) complications can be seen in patients with leukemia, depending on the disease itself and the chemotherapeutic agents used. This study focused on CNS complications during treatment in children with acute leukemia in a single pediatric institution. METHODS: CNS complications were evaluated retrospectively in 115 patients with ALL and AML. Patients with CNS leukemia infiltration at the time of diagnosis or during a neurological event, late-onset encephalopathy, peripheral neuropathy, or a previous history of neurological abnormalities were excluded from the study. RESULTS: A total of 115 children's clinical records with acute leukemia over a four-year period were reviewed. Acute CNS complications developed in 23.1% of acute myeloid leukemia (AML) patients and in 13.5% of acute lymphoblastic leukemia (ALL) patients. CNS complications developed most frequently during the induction phase of the treatment (66.7%). Seizures were the most common symptom (9 patients, 50%), followed by hemiparesis (4 patients, 22.2%) and headache (4 patients, 22.2%). Six patients (33.3%) had chemotherapy-induced toxic leukoencephalopathy, two (11.1%) had Wernicke's encephalopathy, and one patient (5.6%) each had sinus vein thrombosis, posterior reversible encephalopathy syndrome, and CNS infection. Sequelae occurred in three patients (16.7%), and only one patient (5.6%) died due to a CNS complication. CONCLUSION: A wide variety of symptoms can be observed in childhood leukemia, depending on the disease itself, the chemotherapeutic agents used and a lot of other conditions such as nutritional problems. Our research shows that several CNS complications might manifest with similar symptoms; differentiated diagnosis between the underlying etiological reasons can be made by neuroimaging.

Evaluation of Oxidative Stress by Dynamic Thiol/Disulfide Homeostasis and Ischemia-Modified Albumin Levels in Children with ß-Thalassemia Major.

OBJECTIVE: ß-thalassemia major (ß-TM) is a hemoglobinopathy characterized by reduced or absent ß-globin production. A balance remains between the production of free radicals and suppression of increased levels of reactive oxygen species by the antioxidant system. This study aimed to examine thiol/disulfide homeostasis (TDH) and serum ischemia-modified albumin (IMA) levels to evaluate the oxidant/antioxidant balance in healthy children and persons with ß-TM receiving and not receiving chelation therapy. METHODS: This prospective study was carried out from January to June 2021 among 46 individuals with ß-TM and 35 healthy controls. A spectrophotometric method was used to analyze TDH and IMA concentrations. RESULTS: We found that, compared to controls, native thiol (NT) (P = .048) and total thiol (TT) (P = .027) values were lower in the patient group, whereas disulfide (P < .001), disulfide/native thiol (D/NT) (P = .004), disulfide/total thiol (D/TT) (P = .005), native thiol/total thiol (NT/TT) (P = .004) and IMA (P = .045) values were higher. NT and TT levels were significantly lower in the chelation- group compared to the chelation+ and control groups (P = .002, P = .001). D/NT, D/TT, and NT/TT levels were higher in the chelation+ group than the control group (P = .007), and IMA levels were significantly higher in the chelation+ and chelation- groups compared to the control group (P = .002). The receiver operating characteristic analysis demonstrated that IMA levels were significantly higher in the children with ß-TM not taking regular chelation therapy. CONCLUSION: Thiol/disulfide homeostasis was observed to be weakened in children with ß-TM in our study. Our findings show that when children with ß-TM do not receive regular chelation therapy, their oxidant imbalance worsens.

A retrospective study of age-defined hematologic inflammatory markers related to pediatric COVID-19 diagnosis.

BACKGROUND: The aim of this study was to examine age-related differences in hemogram parameters and hematologic inflammatory markers in pediatric patients with COVID-19. METHODS: This retrospective study included children aged 2 months to 18 years (n = 208) who have a confirmed diagnosis of COVID-19 and a control group comprising 117 healthy children between February 2021 and July 2021. The analysis of subgroup hematological values were performed according to the children's age cutoffs. RESULTS: The most significant difference between pediatric patients with COVID-19 and controls were peripheral blood eosinophil counts and eosinophil-to-monocyte ratio (EMR) levels on admission. The levels of monocyte-to-lymphocyte ratio, aggeregate index of systemic inflammation (neutrophil × platelet × monocyte/lymphocyte), neutrophil-to- lymphocyte × platelet ratio, and systemic inflammation response index (neutrophil × monocyte/ lymphocyte) were higher in patients than in controls. EMR had the highest area under the curve (AUC) value of 0.777, with a cutoff value of 0.26. The sensitivity for EMR was 75% under 2 years of age, and between 78.6-87.5% in the other age groups. CONCLUSION: In children younger than 6 months, the discriminative power of hematological indices is low, while the discriminative power of EMR is high at all ages when age appropriate cutoffs are used. Hematological inflammatory parameters may be particularly practical in pediatric clinics to help identify COVID-19 infection.

Treatment of intrathecal methotrexate overdose with folinic acid rescue and lumbar cerebrospinal fluid exchange: A report of two cases.

We report two male cases (4- and 5-years-old) of intrathecal methotrexate overdose. The two boys with acute lymphoblastic leukemia were to receive intrathecal injection of methotrexate. Instead of the prescribed 12 mg, they both received a dose of 120 mg. The initial cerebrospinal fluid samples showed methotrexate concentration of 2.24x10-2M in case 1 and 1.32x10-2M in case 2. The cases were successfully treated with cerebrospinal fluid (CSF) exchange and intravenous folinic acid rescue. The favorable outcome in our cases suggests that CSF exchange is safe and that folinic acid rescue may be adequate to prevent sequelae in patients subjected to intrathecal MTX overdoses up to 120 mg. We propose CSF exchange and intravenous folinic acid as the mainstay of treatment. In addition to the staff's failure to check the drug label carefully, the marked resemblance of the two dose preparations of MTX may have been contributory.

Evaluation of cardiac function in healthy children native to 1890 metres.

OBJECTIVE: The aim of the study is, by comparing cardiac parameters between children native to 1890 metres with children living at sea level, to find out whether there is any impairment in cardiac function related to that altitude. METHODS: Electrocardiographic, conventional, and tissue Doppler echocardiographic parameters were compared in 42 healthy children native to 1890 metres, and in 21 healthy age and gender matched children living at sea level. Plasma haemoglobin level and oxygen saturation measured by pulse oxymeter were also obtained from all patients. RESULTS: Haemoglobin levels were higher, and oxygen saturation levels were lower in children native to 1890 metres. Conventional echocardiographic parameters and mitral annular myocardial parameters were all similar between children native to 1890 metres and children living at sea level. Tricuspid lateral annular early diastolic velocity and the ratio of early-to-late diastolic velocity were significantly lower and tricuspid lateral annular izovolumetric relaxation time was significantly higher in children native to 1890 metres than children living at sea level. CONCLUSION: Children living at 1890 metres of altitude predispose to asymptomatic right ventricular diastolic dysfunction or otherwise they remain as healthy children.

Optical coherence tomography angiography findings in young ß-thalassemia patients.

PURPOSE: The purpose was to evaluate retinal vascular parameters by optical coherence tomography angiography in ß-thalassemia major patients. METHODS: Thirty-three patients with ß-thalassemia major (study group) and 29 healthy children (control group) were enrolled in the study. All subjects underwent a complete ocular examination. The mean foveal avascular zone, non-flow area, foveal avascular zone perimeter, acircularity index of foveal avascular zone, foveal density, the superficial capillary plexus, and deep capillary plexus were scanned using 6 × 6 mm optical coherence tomography angiography scans centered on the macula. Superficial capillary plexus and deep capillary plexus were also scanned centered on the optic disk. We collected data on histories of patients, and hemoglobin and ferritin were also studied from both groups. RESULTS: The mean age was 13.85 ± 4.69 years (range: 4-21 years) in ß-thalassemia major group and 12.59 ± 3.66 years (range: 6-18 years) in the control group. The mean foveal avascular zone value was 0.265 ± 0.11 mm2 in the study group and 0.296 ± 0.12 mm2 in the control group. The mean non-flow area value was 0.468 ± 0.12 mm2 in the study group and 0.479 ± 0.14 mm2 in the control group (p > 0.05). Differences in the mean values for foveal density and acircularity index were statistically significant between the study group and control group (p < 0.05, p = 0.026, and p = 0.026, respectively). Superficial capillary plexus and deep capillary plexus were not a significant difference between the study and control groups in 6 × 6 mm scans on macula and 4.5 × 4.5 mm scans on optic disk area (p > 0.05). Acircularity index was negatively correlated (r = -0.292, p = 0.026), and foveal density was positively correlated with hemoglobin (r = 0.292, p = 0.026). CONCLUSION: By using optical coherence tomography angiography, we detected foveal microvascular changes in young ß-thalassemia patients before significant ocular anomalies development.

Malignancy-associated hemophagocytic lymphohistiocytosis in pediatric cases: a multicenter study from Turkey.

This study evaluates the clinical and laboratory data of children with secondary hemophagocytic lymphohistiocytosis (sHLH) related to malignancy. Charts of patients who met the diagnostic criteria for sHLH associated with malignancy between January 2000-2006 at six different hospitals in Turkey were reviewed retrospectively. The diagnosis of HLH had been established by bone marrow aspiration in 27 patients, cerebrospinal fluid and bone marrow aspiration in one patient and lung-liver biopsy in another. Twenty-nine children were diagnosed as having sHLH related to malignancy. Twenty cases (18 ALL and 2 AML) with acute leukemia (10 girls/10 boys, median age: 8 years [3-14 years]) were found to have sHLH. Five patients with acute leukemia had HLH at the time of diagnosis (Group 1a), and 15 patients with acute leukemia were diagnosed as having sHLH during therapy (Group 1b), namely reactive sHLH associated with the chemotherapy. Nine patients, including two cases each of rhabdomyosarcoma, neuroblastoma, Hodgkin disease, and non-Hodgkin lymphoma (NHL) and one case with Langerhans cell histiocytosis, were diagnosed as having concomitant hemophagocytosis at the initial evaluation of the tumor (Group 2). Fever, anemia, and hypertriglyceridemia were present in all sHLH cases of all three groups. Hepatomegaly was detected in 60.0%, 73.3%, and 88.8% of the three groups, respectively. Splenomegaly was more frequent in patients of Groups 1a (60.0%) and 2 (88.8%) than in those of Group 1b, the reactive ones (13.3%). Hypofibrinogenemia was detected in all patients of Group 1a and Group 2. Low level of fibrinogen was present in 91.6% of patients in Group 1b. All patients in Group 1b (100%) had neutropenia and thrombocytopenia. Neutropenia was found at rates of 60.0% and 55.5% in Group 1a and Group 2, respectively. Thrombocytopenia was detected in 80.0% of patients in Group 1a and 77.7% in Group 2. The overall mortality rate was 34.4% (10 cases) in our series of 29 children with sHLH; 50% of deaths were directly attributable to HLH. Pediatric malignancy-associated HLH patients have been commonly described as case presentations or in a review of the literature. We believe that our cohort, compiling 29 children regarding the association between malignancy and HLH, will be useful for pediatricians who are interested in this still mysterious topic.

Assessment of the results of a three-year program for National Standardization and Quality Improvement of Medical Laboratories on Drug of Abuse Testing by the Ministry of Health in Turkey.

The aim of this study is to assess the results of inspections in the last three years of drug abuse testing in medical laboratories according to the latest regulations in Turkey. The on-site inspections of medical laboratories for drugs abuse testing performed in Alcohol and Drug Addiction Treatment Centers during 2014-2016 are described, and laboratory processes and performance evaluated. The performance of 35 laboratories in 2014, 62 laboratories in 2015, and 94 laboratories in 2016 were scored as the sum of the scores for all answers on the inspection form. An inspected laboratory was considered to have an unconformity if the total score was less than 2/3 of maximum score. The total scores of inspections and the number of laboratories with between years were compared using one-way analysis of variance and slope Chi-square for trend test, respectively. Total scores increased statistically significantly from 35.9 ± 16.2 in 2014, to 43.5 ± 16.3 in 2015 and 49.1 ± 1.3 in 2016 (p < 0.001). The laboratories with unconformities decreased statistically significantly from 57% in 2014 to 37% in 2015 and 22% in 2016 (p < 0.001). The published legislation and the inspections contributed to national standardization and improved quality of service in medical laboratories for drug abuse testing.

Factor 8 (F8) gene mutation profile of Turkish hemophilia A patients with inhibitors.

Factor VIII (FVIII) replacement therapy is ineffective in hemophilia A patients who develop alloantibodies (inhibitors) against FVIII. The type of factor 8 (F8) gene mutation, genes in the major histocompatibility complex loci, and also polymorphisms in IL-10 and tumor necrosis factor-alpha are the major predisposing factors for inhibitor formation. The present study was initiated to reveal the F8 gene mutation profile of 30 severely affected high-responder patients with inhibitor levels of more than 5 Bethesda U (BU)/ml and four low-responder patients with inhibitors less than 5 BU/ml. Southern blot and PCR analysis were performed to detect intron 22 and intron 1 inversions, respectively. Point mutations were screened by DNA sequence analysis of all coding regions, intron/exon boundaries, promoter and 3' UTR regions of the F8 gene. The prevalent mutation was the intron 22 inversion among the high-responder patients followed by large deletions, small deletions, and nonsense mutations. Only one missense and one splicing error mutation was seen. Among the low-responder patients, three single nucleotide deletions and one intron 22 inversion were found. All mutation types detected were in agreement with the severe hemophilia A phenotype, most likely leading to a deficiency of and predisposition to the development of alloantibodies against FVIII. It is seen that Turkish hemophilia A patients with major molecular defects have a higher possibility of developing inhibitors.