Varicella-Zoster Virus Reactivation After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation, Single-Center Experience of Acyclovir Prophylaxis.

BACKGROUND: Varicella-zoster virus (VZV) reactivation is the most common infectious complication in the late posthematopoietic stem cell transplantation (HSCT) period and is reported as 16%-41%. Acyclovir prophylaxis is recommended for at least 1 year after HSCT to prevent VZV infections. However, studies on the most appropriate prophylaxis are ongoing in pediatric patients. METHODS: Patients who underwent allogeneic HSCT between January 1, 1996 and January 1, 2020 were retrospectively analyzed to outline the characteristics of VZV reactivation after allogeneic HSCT in pediatric patients using 6 months acyclovir prophylaxis. RESULTS: There were 260 patients and 273 HSCTs. Median age was 10.43 (0.47-18.38), and 56% was male. Median follow-up was 2325 days (18-7579 days). VZV reactivation occurred in 21.2% (n = 58) at a median of 354 (55-3433) days post-HSCT. The peak incidence was 6-12 months post-HSCT (43.1%). Older age at HSCT, female gender, history of varicella infection, lack of varicella vaccination, low lymphocyte, CD4 count, and CD4/CD8 ratio at 9 and 12 months post-HSCT was found as a significant risk for herpes zoster (HZ) in univariate analysis, whereas history of varicella infection and low CD4/CD8 ratio at 12 months post-HSCT was an independent risk factor in multivariate analysis. CONCLUSIONS: Tailoring acyclovir prophylaxis according to pre-HCT varicella history, posttransplant CD4 T lymphocyte counts and functions, and ongoing immunosuppression may help to reduce HZ-related morbidity and mortality.

The effect of intravenous ondansetron on QT interval in the emergency department.

OBJECTIVE: Ondansetron, a 5HT3 receptor antagonist, is commonly used in emergency departments to treat nausea and vomiting. In 2011, the Food and Drug Administration (FDA) issued a warning that this medicine may cause QT prolongation, potentially leading to deadly arrhythmias. The objective of this study was to characterize the QT interval prolongation associated with ondansetron use in the Emergency Department. METHODS: This was a prospective, observational cohort study of adult patients who presented to the emergency department during a one-year period and were treated with intravenous ondansetron. We investigated the QT prolongation associated with dosages. ECGs were obtained before the medication and 5, 15, and 30 minutes after IV drug administration. Every QT measurement was recorded and compared to the zero point. The severity of drug-induced QT prolongation was determined according to the recommendations of the International Conference on Compliance (ICH). QTc prolongation was categorized as 'negligible' (<5 ms), 'significant' (>20 ms), 'potential concern' (>30 ms), or 'definitely worrying' (>60 ms). RESULTS: Of the 435 patients enrolled in the study, 60% (261 patients) were female and the mean age was 39 (±18). The QT prolongation peaked at the fifth minute and remained consistent at the fifteenth and thirty-first minutes. The maximum prolongation of the mean QT duration occured at the fifth minute (7.9 ± 18.1 ms). No patient revealed any problems with cardiac conduction. The prolonged QT interval was not related to the dose of ondansetron, but QT measurements were higher in the 30th minute in patients treated with 8 mg of ondansetron. The effect of ondansetron administration on QT prolongation was found to be above the 'negligible' but below the 'significant' value, according to the ICH recommendations. DISCUSSION: In this study, QT prolongation due to ondansetron administration was below the 'important' value according to the recommendations of the ICH. No cases of cardiac arrhythmia were reported in any of the partients. Thus, routine ECG monitoring in patients given ondansetron due to the risk of QTc prolongation does not seem cost-effective when evaluated together with additional factors such as its negative impact on emergency patient flow, waste of personnel and time, and increase in healthcare costs. In the absence of a known risk of cardiac arrhythmia, IV administration of 4 mg and 8 mg of ondansetron doses no risk of QT prolongation in the emergency population.

Evaluation of paediatric herpes zoster cases: Comparison of herpes zoster attacks in children with and without underlying conditions.

AIM: Herpes zoster is rarely seen in children, but is more common and more severe in those with underlying medical conditions. The purpose of this study was to comprehensively evaluate cases of herpes zoster in all paediatric patients and to detail the clinical course and complications of this disease in children with and without underlying health problems in terms of similarities and differences. METHODS: The course of paediatric patients diagnosed with herpes zoster in a tertiary university hospital over a 19-year period was evaluated from the time of diagnosis, divided into groups with and without underlying disease. RESULTS: In our study, where we evaluated 150 herpes zoster attacks in 143 children, 79.3% of the patients (n = 119) had underlying diseases, while 20.7% (n = 31) were healthy children. The age at the time of primary varicella-zoster virus and herpes zoster was significantly younger in the group without an underlying disease compared to the group with an underlying disease. Pain was reported more in the healthy group, and the duration of symptoms was longer. Ophthalmic nerve involvement was significantly higher in the group without a known disease. Treatment was administered in 90% of all attacks. In the group with underlying diseases, the duration of intravenous treatment and hospital stay were significantly higher as expected. CONCLUSIONS: This study shows that herpes zoster attacks in healthy children can also progress with severe symptoms and complications. Approaches to reduce the burden of herpes zoster should be adopted and developed for all paediatric patients.

Evaluation of stabbing assault injuries in a tertiary emergency department: a retrospective observational study.

BACKGROUND: Approximately 458,000 victims were deceased from intentional violence in 2021. A stabbing assault causes 25% of homicides. The study aims to evaluate injury patterns, trauma scores, radiological findings, types of treatment, and outcomes of stab assault patients admitted to a tertiary emergency department (ED). METHODS: This is a retrospective observational study of stabbing injury patients in the ED of Hacettepe University, Turkey. The sites and patterns of injury, radiological findings, treatment methods, consultations, and complications are acquired from the patient's files. Trauma scores and frequency of outcomes, such as the need for surgery, hospitalization, or mortality, were calculated for all patients. RESULTS: Among the 648 patients, 564 (87%) were male. The median age was 28 (interquartile range [IQR]:13). The commonly injured body parts were the extremities (75%), thorax (21.9%), and abdomen (16.9%). The median RTS was 7,84 (IQR:0), and the median ISS was 2 (IQR:3). The fluid was detected in 13 of 88 patients by FAST, solid organ injuries in 21 patients, and gastric and intestinal injuries in 11 patients by abdominal CT. One hundred sixty-one patients underwent moderate and major surgery. Complications developed in 13 patients. 74,4% of the patients (n = 482) were treated in ED and 21.8% (n = 141) of patients were hospitalized in wards, 2.3% (n = 15) in intensive care unit and 1.5% (n = 10) patients died. GCS, RTS, and probability of survival (Ps) were significantly lower, and ISS was significantly higher in deceased patients and patients who needed erythrocyte replacement. CONCLUSION: The majority of stab wounds were detected in extremities, but severe and lethal stabbing injuries were on the thorax and abdomen. In thoracoabdominal stabbing injuries, x-rays and FAST can be ineffective in detecting critical and fatal injuries. Therefore, thoracic and abdominal CT should be planned early to detect possible causes of death and make a timely and accurate diagnosis. Lower GCS, RTS, and Ps or higher ISS scores were related to the need for erythrocyte replacement.

Evaluation of the reliability and accuracy of YouTube™ and TikTok™ contents about storage media for avulsed teeth: A cross-sectional study.

BACKGROUND/AIMS: The preservation of avulsed teeth is critical in dental trauma management, necessitating effective storage media to ensure viable tooth reimplantation. The urgent need for accurate information has led both professional and non-professional individuals to increasingly seek guidance from video-sharing platforms such as YouTube™ and TikTok™. These platforms have become key resources for advice on such dental emergencies, but the reliability and accuracy of this information have not yet been systematically evaluated. This study aimed to assess the quality, accuracy, and reliability YouTube™ and TikTok™ of videos regarding storage solutions for avulsion injuries. MATERIAL AND METHODS: A search was conducted on YouTube™ and TikTok™ on February 4th, 2023, using terms related to traumatic dental injuries, and 53 videos were included. Video demographics such as platform, duration, type, upload date, likes, and comments were recorded. Video content quality, reliability, and accuracy were measured using the Global Quality Scale (GQS), Journal of the American Medical Association (JAMA) benchmarks, and Video Information and Quality Index (VIQI). Research data were analyzed using SPSS IBM 24.0 at a 95% confidence interval. RESULTS: In total, 53 videos were examined. The average scores were JAMA: 1.70/4.00, modified DISCERN: 54.3/80.00, GQS: 3.88/5.00, and VIQI: 13.8/20.00. According to the modified DISCERN index, there were no "very poor" or "poor" quality videos, 49.05% were "moderate," 22.6% were "good," and 28.3% were "very good." No difference was found between YouTube™ and TikTok™ videos in terms of the modified DISCERN index, JAMA scores, GQS, and VIQI scoring (p > .05). CONCLUSIONS: Traumatic dental injuries are a common problem among children, and evaluating the reliability of available contents is becoming crucial for appropriate intervention. The study reveals that despite being sourced mainly from dental professionals, the overall quality of videos on avulsed tooth management was mediocre, underscoring the risks associated with misleading or incomplete information in such critical situations.

Quality and Reliability of YouTube Video Contents About Sports Mouthguards: A Cross-Sectional Study.

BACKGROUND: Sports dentistry aims to prevent and manage orofacial injuries, tooth fractures, tooth loss, and soft tissue trauma during sport activities. Mouthguards are appliances that protect athletes from dental trauma during contact sports. The video-sharing platform YouTube has a large number of informative videos about mouthguards. This study aimed to analyze the quality, accuracy, and reliability of YouTube videos about mouthguards, investigate the relationship between the features and the quality of mouthguard videos on YouTube, and provide suggestions for future informative content about mouthguards and sports dentistry. MATERIALS AND METHODS: The first 100 videos for each keyword from YouTube were collected using the keywords "mouthguard," "sports mouthguard," and "mouthguard and dental trauma." Videos meeting the inclusion criteria were categorized based on publisher (dental professionals and nonprofessionals) and type (animation/slideshow, interview, and product introduction). Video features were recorded. Video content quality, reliability, and accuracy were measured by the Video Information and Quality Index (VIQI), the Journal of the American Medical Association (JAMA) benchmarks, the DISCERN Instrument, the Global Quality Scale (GQS), and the usefulness score. Data were analyzed using SPSS (IBM 29.0) at a 95% statistical significance level (p = 0.05). RESULTS: Out of 300 videos, 80 videos were included. Most of the videos were uploaded by dental professionals (n = 49). The average values of the VIQI, JAMA, DISCERN, and GQS scores were 15.33 out of 20.0, 1.38 out of 4.00, 49.24 out of 80.0, and 2.99 out of 5.00, respectively. Videos uploaded by dental professionals had significantly higher scores in VIQI, JAMA, DISCERN, GQS, and usefulness scores but exhibited a lower number of likes, comments, and views (p < 0.05). Of all included videos, 51% (n = 41) were categorized as "moderately useful" and 10% (n = 8) as "very useful." CONCLUSIONS: Mouthguard videos uploaded by dental professionals are more useful, accurate, and of higher quality. Therefore, patients should consider the information shared by dental professionals. Greater participation from dentists in sharing high-quality content would be beneficial.

Further treatment of coking wastewater treated in A2O-MBR by the nanofiltration-powder activated carbon hybrid system.

In this study, further treatment of coking wastewater treated in anoxic-oxic-membrane bioreactor (A2O-MBR) was investigated to meet the standards of the ministry by means of nanofiltration (NF) (with two different membranes and different pressures), microfiltration -powder activated carbon (MF-PAC) hybrid system and NF-PAC (with two different membranes and five different PAC concentrations) hybrid system. In addition to the parameters determined by the ministry, other parameters such as ammonium, thiocyanate (SCN-), hydrogen cyanide (HCN), dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), color were also examined to evaluate the flux performance and treatment efficiency of the hybrid processes. According to the results, chemical oxygen demand (COD) in the NF process, COD and total cyanide (T-CN) in the MF-PAC process could not meet the discharge standards. As for the NF-PAC hybrid system, XN45 membrane met the discharge standards in all parameters (COD = 96±1.88 mg/L, T-CN =<0,02 mg/L, phenol =<0.05 mg/L), with a recovery rate of 78% at 0.5 g/L PAC concentration.

Evaluation of the genotoxicity, cytotoxicity, and bioactivity of calcium silicate-based cements.

BACKGROUND: As calcium silicate-based cements (CSCs) have found success in various vital pulp therapy applications, several new CSC products have emerged. This study aimed to assess the genotoxicity, cytotoxicity, and bioactivity of four CSCs by comparing the newly introduced materials Bio MTA+ and MTA Cem with previously studied materials, Biodentine and NeoMTA. METHODS: Genotoxicity was evaluated using the micronucleus (MN) assay in human peripheral blood lymphocyte cells, measuring MN frequency and nuclear division index (NDI). Cytotoxicity was assessed in human dental pulp stem cells through the Water-Soluble Tetrazolium Salt-1 (WST-1) colorimetric assay. Bioactivity was determined by ELISA, measuring the levels of angiogenic and odontogenic markers (BMP-2, FGF-2, VEGF, and ALP). Statistical analyses included ANOVA, Dunnet and Sidak tests, and Wald chi-square test. (p < .05). RESULTS: The MN frequency in the groups was significantly lower than that in the positive control group (tetraconazole) (p < .05). NDI values decreased with increasing concentration (p < .05). Bio MTA+ and NeoMTA showed decreased cell viability at all concentrations in 7-day cultures (p < .01). All materials increased BMP-2, FGF-2, and VEGF levels, with Biodentine and NeoMTA showing the highest levels of BMP-2 and FGF-2 on day 7. Biodentine displayed the highest VEGF levels on day 7. Biodentine and NeoMTA groups exhibited significantly higher ALP activity than the Bio MTA+ and MTA Cem groups by day 7. CONCLUSION: Bio MTA+ and MTA Cem demonstrated no genotoxic or cytotoxic effects. Moreover, this study revealed bioactive potentials of Bio MTA+ and MTA Cem by enhancing the expression of angiogenic and osteogenic growth factors.

The Determining Factors for Outcome of Pediatric Intensive Care Admitted Children After Stem Cell Transplantation.

INTRODUCTION: Requiring pediatric intensive care unit (PICU) admission relates to high mortality and morbidity in patients who received hematopoietic stem cell transplantation (HSCT). In this study, we aimed to evaluate the indications for PICU admission, treatments, and the determining risk factors for morbidity and mortality in patients who had allogeneic HSCT from various donors. MATERIALS AND METHODS: In this retrospective study, we enrolled to patients who required the PICU after receiving allogeneic HSCT at our Pediatric Bone Marrow Transplantation Unit between 2005 and 2020. We evaluated to indication to PICU admission, applications, mortality rate, and the determining factors to outcomes. RESULTS: Thirty-three (7%) patients had 47 PICU admissions and 471 patients underwent bone marrow transplantation during 16-year study period. Also, 14 repeated episodes were registered in 9 different patients. The median age of PICU admitted patients was 4 (0.3 to 18) years and 29 (62%) were male. The main reasons for PICU admission were a respiratory failure, sepsis, and neurological event in 20, 8, and 7 patients, respectively. The average length of PICU stay was 14.5 (1 to 80) days, 14 (43%) of patients survived and the mortality rate was 57%. Multiple organ failure ( P =0.001), need for respiratory support ( P =0.007), inotrope agents ( P =0.001), and renal replacement therapy ( P =0.013) were found as significant risk factors for mortality. CONCLUSIONS: Allogeneic HSCT recipients need PICU admission because of its related different life-threatening complications. But there is a good chance of survival with quality PICU care and different advanced organ support methods.

Thalassemia patients in transfussion dependent period and after hematopoietic stem cell transplantation: how are the psychiatric status and life quality of these patients?

Although hematopoietic stem cell transplantation (HSCT) has been widely used to treat patients with beta-thalassemia major, evidence showing whether this treatment improves mental health, self esteem and health-related quality of life (HRQoL) is limited. We aimed to describe psychiatric problems, HRQoL and self-esteem scores of patients who have thalassemia and compared with patients who underwent HSCT in the current study. A total of 24 patients with thalassemia major and 13 patients who underwent HSCT at least 2 years ago aged between 7-37 years were included. We used The Children's Depression Inventory, The Spielberger State-Trait Anxiety Inventory, and Pediatric Quality of LifeTM (PedsQL™) for assesment of children and Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), World Health Organization Quality of Life Scale Brief Version (WHOQOL-BREF) for assessment of adults. We also used Piers Harris Self Concept Scale for children and adults. Psychopathologies are common in both groups (50% in Thalassemia group and 69.2% in HSCT group). Popularity scores in Piers Haris scale of patients in HSCT group were significantly higher compared to thalassemia group (p = 0.03). Additionally, HSCT group had higher scores in physical health subscales of HRQoL in both children and parents'(p = 0.02, p = 0.03 respectively). Our findings suggest improved HRQoL and self-esteem in thalassemia patients after HSCT. However, due to the high prevalence of mental disorders in both groups, we would like to emphasize that clinicians should examine not only the physical but also the psychological state of the patients with thalessemia during the their treatment and follow-up period after HSCT.

Tissue Plasminogen Activator Use in Pediatric Patients: A Single Center Experience.

INTRODUCTION: Thrombosis is rare in children and antithrombolytic treatment is controversial. Most commonly used thrombolytic agent is tissue plasminogen activator (t-PA) in pediatrics. In this study, we report our experience in the use of thrombolytic treatment. METHODS: Eighteen patients who had received systemic t-PA between January 2006 and December 2013 were recorded. The response to t-PA was evaluated as complete, partial, and no. The bleeding complication during t-PA administration was graded as minor or major. RESULTS: There were 18 patients (2 mo to 12 y) who received systemic t-PA. Three patients had venous, 14 patients had arterial, and 1 patient had intracardiac thrombosis. Thrombosis was related to cardiac catheterization (61.1%), central venous catheterization (16.7%), cardiac surgery (11.1%), and arrhythmia (5.5%). In 1 patient thrombosis occurred spontaneously (5.5%). Eighteen patients received 25 courses of systemic t-PA (0.15 to 0.3 mg/kg/h). A total of 55.6% of cases had complete, 27.8% had partial, and 16.6% showed no resolution. CONCLUSION: t-PA infusion at doses of median 0.2 mg/kg/h (0.15 to 0.3) seems effective and safe. There is still no consensus on indications and dosing of antithrombolytic treatment in children but in selected patients it decreases long-term complications due to thrombosis.

A Novel PUS1 Mutation in 2 Siblings with MLASA Syndrome: A Review of the Literature.

ABSTRACT: Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) is a rare mitochondrial disorder characterized by MLASA. Variable features of this condition include failure to thrive, and developmental delay or intellectual disability. Additional symptoms consist of cognitive impairment, skeletal and dental abnormalities, delayed motor milestones, cardiomyopathy, dysphagia, and respiratory insufficiency. MLASA has previously been associated with mutations in pseudouridylate synthase 1 (PUS1) and YARS2. PUS1 encodes the nuclear PUS1 enzyme, which is located in both the nucleus and the mitochondria. PUS1 converts uridine into pseudouridine in several cytosolic and mitochondrial transfer RNA positions and increases the efficiency of protein synthesis in both compartments.In the present report, we report on 2 Turkish sisters 4 and 11 of years with an MLASA plus phenotype. Both patients have sideroblastic anemia, lactic acidosis, failure to thrive, developmental delay, and chronic diarrhea; in addition, the older sister has strabismus and skeletal anomalies. The sequencing of the PUS1 gene revealed a novel homozygous p.Glu311* mutation. The phenotype of the older sibling is also unique because of the strabismus and skeletal anomalies, when compared with her sister and other previously reported patients with MLASA. The structural differences in the nuclear versus mitochondrial isoforms of PUS1 and modifier genes may be implicated in the variability of the clinical presentations in MLASA. CONCLUSION: This report adds to the growing number of mutations causing complex clinical manifestations of MLASA including lactic acidosis, sideroblastic anemia, chronic diarrhea, and myopathy.

Risks and outcomes of invasive fungal infections in pediatric allogeneic hematopoietic stem cell transplant recipients receiving fluconazole prophylaxis: a multicenter cohort study by the Turkish Pediatric Bone Marrow Transplantation Study Group.

Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P = .011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P = .012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P = .014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P = .007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P = .063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%.The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.

Aromatase inhibition by 2-methyl indole hydrazone derivatives evaluated via molecular docking and in vitro activity studies.

A causal association is reported between prolonged exposures to elevated levels of estrogen and breast cancer. Therefore inhibiting aromatase (CYP19A), which catalyses the conversion of androgens to estrogens, is an important approach in prevention and treatment of estrogen receptor positive (ER+) breast cancer. Melatonin, a natural indolic hormone, is reported to prevent free radical induced carcinogenesis and block local estrogen synthesis in breast tissue via aromatase inhibition. However several features of melatonin limit its therapeutic use. In the present study aromatase inhibiting potential of 2-methyl indole hydrazones are investigated, and compared with melatonin, by two in vitro models; a cell-free assay using a fluorescence substrate and a cell-based assay where cell proliferation was determined in ER + human breast cancer cells (MCF-7 BUS) in the absence of estrogen and the presence of testosterone. Aromatase inhibitory effect is also explored by molecular modelling studies. In biological activity assays monochloro substituted indole hydrazones were found to have stronger aromatase inhibitory activity among all tested derivatives and were more active than melatonin. This finding is further confirmed by molecular modelling. These results may be useful in the design and synthesis of novel melatonin analogues with higher inhibitory potency against aromatase.

Bloodstream infections in pediatric hematology/oncology patients: Six years' experience of a single center in Turkey

Background/aim: Bloodstream infections are the major cause of morbidity, increased cost, prolonged hospitalization, and mortality in pediatric patients. Identifying the predominant microorganisms and antimicrobial susceptibilities in centers helps to select effective empirical antimicrobials which leads to positive clinical outcomes. We aimed to identify the causative microorganisms and their antimicrobial susceptibilities in patients with bloodstream infections. Materials and methods: Data belonging to patients with hematological and/or oncological diseases admitted to our hospital with fever between January 2010 and November 2015 were analyzed. Results: In total, 71 patients who had 111 bloodstream infection episodes were included. Responsible pathogens were detected as follows: 35.1% gram-positive microorganisms, 60.5% gram-negative bacteria, and 4.4% fungi. The most common causative gram-negative pathogen was Escherichia coli and the most commonly isolated gram-positive microorganism was coagulase-negative staphylococci. Conclusion: Gram-negative microorganisms were predominant pathogens in bloodstream infections. Escherichia coli and coagulase-negative staphylococci were the most commonly isolated responsible pathogens. Beta-lactam/lactamase inhibitors were suitable for empirical treatment. However, in critical cases, colistin could have been used for empirical treatment until the culture results were available. Routine glycopeptide use was not required. By identifying the causative microorganisms and their antimicrobial resistance patterns, it will be possible to obtain positive clinical results.

Toxicity of Vincristine Combined With Posaconazole in Children With Acute Lymphoblastic Leukemia.

BACKGROUND: Vincristine (VCR) is one of the main drugs of acute lymphoblastic leukemia (ALL) treatment. Azole antifungal medications are used for treatment or prophylaxis of invasive fungal infections in acute leukemia. Coadministration of these drugs increases the risk of VCR toxicity. OBSERVATIONS: We presented a girl with ALL using posaconazole prophylaxis. She developed VCR toxicity that included tubulopathy, high blood pressure, neuropathic pain, difficulty walking, diffuse muscular weakness, constipation, abdominal pain. CONCLUSIONS: There are limited data in children with ALL for posaconazole prophylaxis. We recommend that VCR side effects should be evaluated by careful monitoring of the patients who are on this combination therapy.

SLCO1B1 Polymorphisms are Associated With Drug Intolerance in Childhood Leukemia Maintenance Therapy.

BACKGROUND: Therapy discontinuations and toxicities occur because of significant interindividual variations in 6-mercaptopurine (6-MP) and methotrexate (MTX) response during maintenance therapy of childhood acute lymphoblastic leukemia (ALL). 6-MP/MTX intolerance in some of the patients cannot be explained by thiopurine S-methyl transferase (TPMT) gene variants. In this study, we aimed to investigate candidate pharmacogenetic determinants of 6-MP and MTX intolerance in Turkish ALL children. METHODS: In total, 48 children with ALL who had completed or were receiving maintenance therapy according to Children's Oncology Group (COG) protocols were enrolled. Fifteen single-nucleotide polymorphisms in 8 candidate genes that were related to drug toxicity or had a role in the 6-MP/MTX metabolism (TPMT, ITPA, MTHFR, IMPDH2, PACSIN2, SLCO1B1, ABCC4, and PYGL) were genotyped by competitive allele-specific PCR (KASP). Drug doses during maintenance therapy were modified according to the protocol. RESULTS: The median drug dose intensity was 50% (28% to 92%) for 6-MP and 58% (27% to 99%) for MTX in the first year of maintenance therapy, which were lower than that scheduled in all patients. Among the analyzed polymorphisms, variant alleles in SLCO1B1 rs4149056 and rs11045879 were found to be associated with lower 6-MP/MTX tolerance. CONCLUSIONS: SLCO1B1 rs4149056 and rs11045879 polymorphisms may be important genetic markers to individualize 6-MP/MTX doses.

Evaluation of engraftment syndrome in children following full-matched related donor hematopoietic stem cell transplantations.

The term "ES" has been widely used for describing a clinical condition consisting of skin rash, fever, and weight gain that occur during neutrophil recovery period following HSCT. In this study, the incidence, clinical features, risk factors, and outcomes of ES were evaluated in 169 children following allogeneic HSCT from full-matched related donor according to the Spitzer criteria. Seventeen patients (10.1%) presented with clinical conditions suggesting ES. In both univariate and multivariate analysis underlying malignant disease and early release of monocytes to the PB, and in univariate analysis using only CsA for GVHD prophylaxis were found to be the significant risk factors for the development of ES. Patients with ES experienced significantly higher incidence of acute and chronic GVHD and propensity toward a higher rate of TRM. OS did not differ between the patient groups. Thirteen of 17 patients received steroid therapy, and all but one patient responded to therapy. Monitoring for early detection of ES and early intervention with steroid therapy is the key for recovery. The most crucial approach for this purpose mainly is to find out and use the most useful and feasible diagnostic criteria for routine medical practice.

Novel indole-based melatonin analogues substituted with triazole, thiadiazole and carbothioamides: studies on their antioxidant, chemopreventive and cytotoxic activities.

Melatonin (MLT) is a well-known free-radical scavenger, involving in the prevention of cellular damage that can lead to cancer, ageing and a variety of neurodegenerative diseases. Research on MLT-related compounds has been required to optimise the maximum pharmaceutical activity with the lowest side effects. In our ongoing research, we have synthesized new indole-based MLT analogues as potential antioxidant agents by modifying the MLT molecule. In this study, we build on previous findings, through the synthesis, characterization and in vitro antioxidant profiling of a series of new indole-based MLT analogues which possess triazole, thiadiazole and carbothioamides on the third position on the indole ring. In vitro antioxidant activity was investigated by evaluating their reducing effect against oxidation of a redox sensitive fluorescent probe and their radical scavenging activity was assessed via the DPPH assay. In addition, in vitro cytotoxic effects of newly synthesized compounds were investigated in CHO-K1 cells using the MTT assay.

The impact of donor age and sex on the nucleated cell count and CD34 count in healthy bone marrow donors.

BM remains an important source of stem cells. The BM characteristics change with age but the estimation of CD34 calculation of one CD34+ cell per 100 nucleated cells is used for all donors including pediatric donors in the operating room before getting the actual CD34 count. In order to see whether this formula is applicable for pediatric donors, we designed a retrospective study to see the affect of the age and sex on the BM NCC, CD34 count, and CD34/NCC ratios. Ninety-eight BM collections from 91 related donors were evaluated retrospectively (median age: nine yr [1.5-54 yr]; M/F: 41/50). A significant negative correlation was found between the donor age and NCC (r = -0.229, p < 0.05), CD34 count (r = -0.563, p < 0.01), and CD34/NCC (r = -0.664, p < 0.01). The negative correlation for CD34 count and CD34/NCC persisted in female and male donor groups. When donors younger than 16 yr of age were compared with the older donor group, the median NCC, median CD34 count, and CD34/NCC were significantly lower in the older group (p < 0.01). Age and sex have to be taken into consideration to avoid unnecessary high-volume collections and increased operating room time in the younger donors.