Therapeutic apheresis: is it safe in children with kidney disease?

BACKGROUND: Therapeutic apheresis (TA) is already used to treat various diseases in the field of nephrology. The aim of this study was to evaluate the frequency and types of complications that occur during TA in children with kidney disease. METHODS: Records of children (≤ 18 years) who underwent TA between 2007 and 2022 were retrospectively reviewed. Children with missing data and those with a diagnosis of nonnephrological disease were excluded. RESULTS: A total of 1214 TA sessions, including 1147 therapeutic plasma exchange (TPE) sessions and 67 immunoadsorption (IA) sessions, were performed on the 108 patients enrolled in the study. Forty-seven percent of the patients were male, and the mean age was 12.22 ± 4.47 years. Posttransplant antibody-mediated rejection (64.8%) and hemolytic uremic syndrome (14.8%) were the most common diagnoses indicating TA. Overall, 17 different complications occurred in 58 sessions (4.8%), and 53 sessions (4.6%) were not completed because of these complications. The distribution of complications among the patients was as follows: 41.4% had technical complications, 25.9% had allergic complications, and 32.7% had others. The most common technical complication was insufficient flow (37.5%). The incidence of complications was greater in patients aged 3-6 years than in patients in the other age groups (p = 0.031). The primary disease, type of vascular access, and rate of fresh frozen plasma/albumin use were similar between patients with and without complications (p values of 0.359 and 0.125 and 0.118, respectively). CONCLUSIONS: Our study showed that complications occurred in only 4.8% of TA sessions. The most common complication was technical problems.

[Investigation of Ganciclovir Resistance in Cytomegalovirus Isolates by Phenotypic and Genotypic Methods]. / Sitomegalovirüs Izolatlarinda Gansiklovir Direncinin Fenotipik ve Genotipik Yöntemlerle Arastirilmasi.

Ganciclovir-resistant cytomegalovirus (CMV) strains are reported following long-term antiviral agent use, especially for immune-suppressive patients. In this study, it was aimed to investigate the mutations in the UL97 gene of CMV, which causes ganciclovir (GCV) resistance by genotypic and phenotypic methods in patients who developed CMV infection following hematopoietic cell (HCT) or solid organ transplantation (SOT). Thirty patients who had HCT or SOT in Mediterranean University Hospital and developed CMV infection during routine follow-up with a viral load of CMV over 1000 copies/mL were included in the study. CMV DNA was analyzed by an automated system (Cobas Ampliprep/COBAS TaqMan CMV Test, Roche Diagnostics, Germany) quantitatively. DNA sequence analysis of the regions including codons 420-664 in the UL97 gene region was done by the Sanger sequencing method to detect mutations causing antiviral resistance and compared with defined mutations. In order to investigate antiviral resistance by phenotypic methods, heparinized blood samples of the patients were collected, 'buffy coat (leukocyte layer)' was inoculated into MRC-5 cells by centrifugation method and CMV growth in these cells was controlled with monoclonal antibodies when growth was detected, virus titer was determined and plaque reduction test was applied as recommended. It was determined that 22 of the 30 patients were HCT recipients and eight were SOT (five kidney, three liver) recipients. When the CMV serology pattern of the patients was evaluated before transplantation, 29 (96.7%) patients were found to be seropositive and one (3.3%) patient was found to be seronegative. Totally, nine CMV UL97 mutations were detected in seven (23.3%) pediatric patients who had HCT, including six seropositive and one seronegative case. In addition, one mutation (D605E) not known to cause GCV resistance was detected in a seronegative recipient and three previously unidentified mutations were detected (1474T, F499S, V559A) in a seronegative recipient. Five of the mutations defined were UL97 mutations with a defined clinical resistance against GCV in each of the five recipients (C603W, C592G, H520Q, M460V, A594T). In the plaque reduction test using 3 µM, 12 µM, 48 µM and 96 µM concentrations of GCV in CMV strains, the IC50 value was determined to be ≥ 8 µM for the five CMV strains, and the phenotypic presence of GCV resistance was shown. Clinical resistance associated with CMV UL97 mutation was detected in five (22.7%) of 22 patients who had HCT. GCV resistance was also demonstrated in these patients by phenotypic methods. No UL97 mutation was detected in the patients who had SOT.

Specific Granule Deficiency Due To Novel Homozygote SMARCD2 Variant.

Background: Specific granule deficiency (SGD) is a rare immunodeficiency associated with CCAT/enhancer-binding protein epsilon (CEBPE) gene variants. It can cause severe recurrent infections and is lethal without successful stem cell transplantation. Few cases with SGD of both type 1 and type 2 have been described in the literature. In this study, we present the first report of a case with a novel homozygous c.511 C > T (p.Gln171Ter) mutation in the SMARCD2 gene of SGD type 2, which was successfully treated with bone marrow transplantation. Case: A male infant presented to our neonatal intensive care unit on the second day of life with an icteric appearance and mild hypotonia. He was evaluated for immunodeficiency as the cause of delayed cord separation and refractory neutropenia. At 6 weeks of age, SGD type 2 with a new variant was diagnosed and successfully treated by bone marrow transplantation. Conclusion: SGD is an immunodeficiency disease that is quite rare. However, we believe that SGD diagnosis and associated new variants can be detected more frequently with the widespread use of all whole-exome sequencing techniques.

Alterations of panoramic radiomorphometric indices in children and adolescents with beta-thalassemia major: A fractal analysis study

Background: Beta-thalassemia major is an inherited disorder that can cause bone deformity and loss of bone mineral density. The objective of this study is to evaluate the cortical and trabecular mandibular bone morphology of children and adolescents who have beta-thalassemia major (ß-TM) using a fractal dimension (FD) analysis and different panoramic radiomorphometric indices with digital panoramic radiographic images (DPRIs).Material and Methods: The study included 80 patients (with 40 patients each of ß-TM and control). The mandibular cortical width (MCW), panoramic mandibular index (PMI), mandibular cortical index (MCI), and simple visual estimation (SVE) were evaluated, and an FD analysis of five regions of interest (ROIs) (ROI 1: in basal cortical bone; ROI 2: in premolar region; ROI 3: in molar region; ROI 4: in angulus mandible and ROI 5: in condyle region) was obtained in all DPRIs. Quantitative variables were analyzed using the student’s t-test , Kruskal–Wallis and Mann-Whitney U tests.Results: When the ß-TM groups were compared with controls, there were no statistically significant differences found in the mean FD values, the ROIs of the trabecular bone, or the SVE. There was a significant correlation in the mean MCW, PMI, ROI of cortical bone (ROI 1), and MCI between ß-TM and control groups (p < 0.001, p < 0.001, p = 0.047, and p = 0.046, respectively). The mean MCW values correlated with the SVE in both the ß-TM and control groups (p = 0.031 and p < 0.001, respectively). While the mean MCW values correlated with the MCI (p = 0.04) in the control group, the mean MCW values were not correlated with the MCI (p = 0.493) in ß-TM group.Conclusions: The current study revealed lower MCW and PMI values in the ß-TM group. While the mean FD values of trabecular bone is similar to the control groups, the mean FD value is lower in cortical bone in the ß-TM group. MCW, PMI, FD of cortical bone and MCI may be key indicators in individuals with beta-thalassemia major.(AU)

Follow-up of human adenovirus viral load in pediatric hematopoietic stem cell transplant recipients.

BACKGROUND: The spectrum of human adenovirus (HAdV)-related disease is broad, and the virus acts on many organs and systems in hematopoietic stem cell transplantation (HSCT) recipients. We aimed to evaluate the effect of HAdV-DNA positivity with clinical and laboratory findings 4 months after HSCT. METHODS AND RESULTS: We retrospectively investigated HAdV-DNA in 153 HSCT recipients (≤18 years) by quantitative real-time polymerase chain reaction (RealStar; Altona Diagnostics). The results of samples from January 2014 to December 2017 are included. HAdV-DNA was positive for at least one sample type in 50 (32.67%) patients. HAdV-DNA positivity rate was 8.92% (N: 145/1625), 40.25% (N: 64/159), and 25% (N: 2/8) for plasma, stool, and urine samples, respectively. HAdV-DNA was positive in the plasma of 38 (24.83%) patients at a median 16 (range: 1-58 days) days after HSCT. The mortality rate was 23.68% and 6.95% in plasma HAdV-positive and HAdV-negative patients (p = .014). Moreover, HAdV-DNA positivity had an impact on overall survival for allogeneic-HSCT (p = .013), with the cumulative effect including graft-versus-host disease state in multivariate analysis (p = .014). CONCLUSIONS: Plasma HAdV-DNA positivity is a potential influencer that decreases survival in the early post-transplant period. Due to the high mortality rates, close monitoring is required of HAdV infections after HSCT with sensitive methods, especially at the early stage.

Investigation of Torque Teno Virus (TTV) DNA as an immunological and virological marker in pediatric hematopoietic stem cell transplantation (HSCT) patients.

BACKGROUND: High viral loads are observed in Torque Teno Virus (TTV) infection after hematopoietic stem cell transplantation (HSCT). We aimed to analyze the kinetics of plasma TTV-DNA load in pediatric patients who received immunosuppressive therapy and developed infection complications in the first 100 days after HSCT. METHODS: As a patient group; 113 plasma samples taken from 33 pediatric HSCT recipients at a time interval after transplantation and as a control group; 38 plasma samples from 38 children without known chronic disease were included in the study. Viral nucleic acid isolation was performed by using the NucliSENS easyMAG (bioMerieux, France) system. A laboratory designed quantitative polymerase chain reaction process was performed on 7300 Real-Time PCR system (Applied Biosystems, CA, USA) with the amplification mixture containing primer and probe sequences for the UTR gene region. RESULTS: TTV-DNA was detected in all patient's samples and the median viral load was calculated as 7.67 Log10 copies/mL (range: 2.84-9.59). In the control group, the TTV-DNA median viral load was calculated as 5.51 Log10 copies/mL (range: 2.50-7.04), except for one negative sample. A significant difference was observed between the control group and the patient group in terms of TTV viral load levels. In nine patients, a median 2.15 Log10 copies/mL viral load increase was observed at 31-60 days post-transplant compared to the pre-transplant period. CONCLUSION: TTV-DNA levels should be closely monitored to understand the immune status of the first 100 days after transplantation and the effects of treatment regimens on patients with HSCT.

TCIRG1 and SNX10 gene mutations in the patients with autosomal recessive osteopetrosis.

Autosomal recessive osteopetrosis (ARO) is a rare genetic bone disease characterized by dense and fragile bone, caused by a defect in osteoclasts responsible for the bone destruction. In this study, we aimed to investigate the mutations in TCIRG1 and SNX10 that are responsible for 50% and 4% of the cases, respectively. All amplicons were sequenced by Sanger sequencing following PCR amplification. As a result, six different mutations of the TCIRG1 gene were found in five of the twelve unrelated cases. These include two novel mutations, namely c.630 + 1G > T mutation and c.1778_1779delTG mutation of the gene which are identified as homozygous. A compound heterozygosity of known mutations c.649_674del26 and c.1372G > A and homozygous presence of the known c.2235 + 1G > A mutation were also observed in different patients. In addition, as a result of the prenatal testing in a family with osteopetrosis infant, the c.1674-1G > A mutation was detected as homozygous for the fetus. In TCIRG1, c.166C > T change, which is indicated as likely benign according to ClinVar database, was heterozygous. Several known polymorphisms; c.117 + 83 T > C, c.417 + 11A > G and c.714-19C > A in TCIRG1 gene; c.24 + 36 T > A and c.112-84G > A in SNX10 gene were also detected. In conclusion, our study revealed that five of the twelve cases carry at least one mutation of TCIRG1 gene. Further studies with more patients and other genes would help better understanding of genetic etiology of the disease.

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.

Decreased Serum Levels of Sphingomyelins and Ceramides in Sickle Cell Disease Patients.

Limited data are available on the serum levels of different sphingomyelin (CerPCho) and ceramide (CER) species in sickle-cell disease (SCD). This study was aimed at identifying the levels of C16-C24 CerPCho and C16-C24 CER in serum obtained from SCD patients and controls. Circulating levels of neutral sphingomyelinase (N-SMase) activity, ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P) were also determined. Blood was collected from 35 hemoglobin (Hb)A volunteers and 45 homozygous HbSS patients. Serum levels of C16-C24 CerPCho and C16-C24 CER were determined by an optimized multiple reaction monitoring (MRM) method using ultrafast liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Serum activity of N-SMase was assayed by standard kit methods, and C1P and S1P levels were determined by enzyme-linked immunosorbent assay. A significant decrease was observed in the serum levels of C18-C24 CerPCho in patients with SCD compared to controls. No significant difference was found in C16 CerPCho levels between the two groups. Very-long-chain C22-C24 CER were significantly decreased in SCD, while long-chain C16-C20 CER levels showed no significant difference between SCD patients and controls. Significant positive correlation was found between the serum total cholesterol levels and C18-C24 CerPCho and C22-C24 CER in SCD patients. Patients with SCD had significantly elevated serum activity of N-SMase as well as increased circulating levels of C1P and S1P compared to controls. The decrease in serum levels of C18-C24 CerPCho in patients with SCD was accompanied by decreased levels of C22-C24 CER. Future studies are needed to understand the role of decreased CerPCho and CER in the pathophysiology of SCD.

Psychopathology in pediatric bone marrow transplantation survivors and their mothers.

BACKGROUND: Bone marrow transplantation (BMT) is used to treat various hematologic, oncologic and metabolic diseases. While the treatment is lifesaving, it is also associated with anxiety, post-traumatic stress disorder, depression and psychosocial problems both in children and parents. METHODS: The aim of this study was to investigate the psychopathology in pediatric BMT survivors and their mothers compared with healthy controls. All children were interviewed using Kiddie Schedule for Affective Disorders and Schizophrenia to assess lifelong psychopathology. For the mothers, the Symptom Checklist-90-Revised (SCL-90-R) was used. RESULTS: In the BMT group, 17 children (63%) had at least one psychiatric disorder, while 15 (53.6%) did in the control group. Although lifelong prevalence of psychopathology in the BMT group did not differ significantly from the control group generally, anxiety disorders were significantly higher in the BMT group. When the SCL-90-R scores of the mothers were compared, Anxiety, Obsessive-Compulsive, Interpersonal Sensitivity and Phobic Anxiety were significantly higher in the mothers in the BMT group, indicating more difficulty in these areas. CONCLUSIONS: Bone marrow transplantation is a significant stressor, especially for mothers. Clinicians should address the child and family as a whole in assessments and be aware of psychiatric symptoms in mothers and children who have had such a life-threatening condition.