The effect of radiotherapy delivery time and obturation materials on the fracture resistance of mandibular premolars.

OBJECTIVES: This ex vivo study was performed to investigate the effect of radiotherapy (RT) delivery time on fracture resistance of mandibular premolars filled with Biodentine or gutta-percha/sealer (GPS). MATERIALS AND METHODS: Seventy-two mandibular premolars were used in this study. Randomly selected 24 teeth were kept intact for the control groups (with and without irradiation). Then, the remaining 48 teeth were randomly assigned into 4 groups (n = 12) according to RT delivery time (irradiated before or after root canal treatment) and obturation materials as follows: Group RT + GPS, Group: GPS + RT, Group RT + Biodentine and Group Biodentine + RT. The samples were either initially endodontically treated and then irradiated or initially irradiated and then endodontically treated with one of the abovementioned materials. The samples were irradiated at 2 Gy per fraction, 5 times a week for a total dose of 60 Gy in 30 fractions over 6 weeks. The roots were embedded in self-polymerizing acrylic resin. The fracture resistance was evaluated in a universal testing machine. Data was analyzed by one-way ANOVA and Games-Howell post hoc test at p < 0.05. RESULTS: Radiation therapy significantly reduced fracture resistance of intact teeth (p < 0.05). The highest fracture resistance was observed in intact/non-irradiated teeth and the lowest fracture resistance in Biodentine + RT group (p < 0.05). The effect of RT delivery time was insignificant when GPS was preferred as the root canal filling material (p > 0.05); it was significant when preferring Biodentine (p < 0.05). When RT was applied to the teeth after Biodentine obturation, the fracture resistance decreased significantly compared to the teeth that were obturated with GPS after or before RT application (p < 0.05). CONCLUSION: Both RT time and obturation materials (Biodentine or gutta-percha/sealer) affect the fracture resistance of the endodontically treated teeth. CLINICAL RELEVANCE: Endodontic treatment could be completed with both materials after RT; however, when the endodontic treatment was initially completed and the teeth were subsequently exposed to RT, it was shown that the reinforcement effect of Biodentine decreased.

The effect of different obturation methods on sealer penetration alongside apically separated rotary nickel-titanium instruments: A confocal laser scanning microscopy study.

The effects of different obturation techniques on calcium silicate-based sealer penetration in the presence of apically separated rotary files were evaluated. Forty-eight extracted mandibular incisors were used. ProTaper F2 rotary files were separated at the apical thirds. Samples were divided into four groups (n = 12) according to obturation technique used: (a) cold lateral compaction (CLC); (b) single cone; (c) bulk-fill (BF) without a core material; and (d) thermoplastic injection (TI). Specimens were sectioned horizontally at 1 and 3 mm from the apex and studied using a confocal scanning laser microscope. The maximum tubule penetration depth and percentage of penetration were measured. Data were statistically analyzed using parametric and nonparametric tests with a significance level of 5%. Regarding penetration depth, a significant difference was found at 1 mm (p < .05), while no significant difference was found at 3 mm (p > .05). At the 3 mm level, all of the obturation techniques showed similar penetration depths. Regarding penetration percentage, the values of the CLC and TI groups were statistically less when compared with the BF group at 1 and 3 mm levels, respectively (p < .05). Under the limitations of this in vitro study, results suggest that the obturation technique may present a significant effect on sealer penetration.

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.

Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Patients in the Black Sea Region of Turkey.

Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11), Chediak-Higashi syndrome (n=2), leukocyte adhesion deficiency (n=2), MHC class 2 deficiency (n=2), chronic granulomatous syndrome (n=2), hemophagocytic lymphohistiocytosis (n=1), Wiskott-Aldrich syndrome (n=1), and Omenn syndrome (n=1). Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.

Invasive fungal infections in children with hematologic and malignant diseases.

BACKGROUND: To evaluate the clinical feature and outcome of invasive fungal infections (IFI) in children with hematologic and malign diseases. PATIENTS AND METHODS: The medical records of children with hematologic and malignant diseases, who were hospitalized at our hospital between January 2010 and December 2011, were reviewed. Proven, probable, and possible IFIs were diagnosed according to the revised definitions of the European Organization for Research and Treatment of Cancer/Mycosis Study Group. The demographic, clinical, and laboratory characteristics of the patients who met the study criteria were evaluated. RESULTS: IFI was diagnosed in 67 (7.2%) febrile episodes of 56 patients, of which 10 (1.2%) were proven, 20 (2%) probable, and 37 (4%) possible IFI. Blood culture of 10 cases with proven IFI yielded yeast and the most common isolated agent was Candida parapsilosis. Seventy percent of cases with fungemia had central venous catheter (CVC). Twenty cases with probable IFI had invasive mold infection. The cases with mold infection had higher median C-reactive protein values, lower neutrophil counts, and longer duration of neutropenia compared with the cases with yeast infection. A total of 14 patients (20.9%) died. Presence of CVC, bone marrow transplantation, total parenteral nutrition, prolonged fever, and proven/probable IFI were detected more often in patients who died, compared with patients who survived. CONCLUSIONS: IFIs are important causes of death in children with hematologic and malignant diseases. Mold infections are seen more frequently in cases with prolonged and profound neutropenia, and invasive yeast infections, especially with non-albicans Candida species, in cases with CVC. Early and effective treatment considering these findings will help to decrease the mortality.

A color and shape based algorithm for segmentation of white blood cells in peripheral blood and bone marrow images.

Computer-based imaging systems are becoming important tools for quantitative assessment of peripheral blood and bone marrow samples to help experts diagnose blood disorders such as acute leukemia. These systems generally initiate a segmentation stage where white blood cells are separated from the background and other nonsalient objects. As the success of such imaging systems mainly depends on the accuracy of this stage, studies attach great importance for developing accurate segmentation algorithms. Although previous studies give promising results for segmentation of sparsely distributed normal white blood cells, only a few of them focus on segmenting touching and overlapping cell clusters, which is usually the case when leukemic cells are present. In this article, we present a new algorithm for segmentation of both normal and leukemic cells in peripheral blood and bone marrow images. In this algorithm, we propose to model color and shape characteristics of white blood cells by defining two transformations and introduce an efficient use of these transformations in a marker-controlled watershed algorithm. Particularly, these domain specific characteristics are used to identify markers and define the marking function of the watershed algorithm as well as to eliminate false white blood cells in a postprocessing step. Working on 650 white blood cells in peripheral blood and bone marrow images, our experiments reveal that the proposed algorithm improves the segmentation performance compared with its counterparts, leading to high accuracies for both sparsely distributed normal white blood cells and dense leukemic cell clusters.

Hemophagocytic bone marrow aplasia with plasma cells in a RAG2-deficient SCID case after a nonconditioned transplantation from a fully matched sibling.

We report a RAG2-deficient patient with severe combined immunodeficiency and hemophagocytic bone marrow aplasia with plasma cells after a nonconditioned transplantation from a fully matched sibling. After engraftment, disseminated BCGosis appeared because of graft versus host disease prophylaxis. On the 55th day, eosinophilia, neutropenia, and thrombocytopenia developed. Aplasia, hemophagocytic histiocytes, and plasma cells were found on his bone marrow with very high level of serum immunoglobulin E. We could not discriminate exactly whether BCGosis or alloimmune response is the cause of hemophagocytic aplasia with plasma cells. Despite the second hematopoietic stem cell transplantation with a reduced intensity conditioning regime, his marrow aplasia did not recover and he died. This case suggests that BCGosis might be associated with hemophagocytic marrow aplasia with plasma cells in an alloimmune reaction.

t(6;9)(p23;q34) presenting acute myeloid leukemia in a child with an unsuspected 45,X/46,X,derY [?t(Yp;Yq)] chromosomal constitution: yet another Y chromosome overdosage and malignancy association.

Development of leukemia in patients with sexual chromosome abnormalities is relatively rare and mostly involves cases of monosomy X, Turner syndrome. Here, we report on a child having a 45,X/46,X,derY [?t(Yp;Yq)] chromosomal constitution (variant Turner syndrome) presenting with concordant acute myeloid leukemia and a rarely seen clonal neoplasic cell lineage-related karyotype, t(6;9)(p23;q34).

Comparison of the approaches to non-febrile neutropenia developing in children with acute lymphoblastic leukemia.

The objectives of this study was to investigate of the influences of high-dose (20 mg/kg/day) methyl prednisolone (HDMP) and granulocyte colony stimulating factor (G-CSF) in shortening the duration of chemotherapy-induced neutropenia encountered in children with ALL receiving maintenance therapy. Sixty-four non-febrile neutropenic attacks developed in 29 patients with ALL receiving St Jude XIII maintenance protocol were evaluated retrospectively. The patients were clinically followed up without drugs for shortening the duration of neutropenia in 21 (32.8%) attacs, while HDMP and G-CSF were administered in 26 (40.6%) and 17 (26.6%) attacks, respectively. After the detection of neutropenia, restoration of neutrophil counts at 2nd or 4th days to the levels that allow resuming the chemotherapy were considered as success. While second day and overall success rates in patients administered HDMP and G-CSF were significantly higher than the patients who were observed clinically. Both second day and overall neutrophil counts were significantly higher in patients administered G-CSF than the other groups. Methyl prednisolone and G-CSF treatments were well-tolerated by the patients. The cost-per neutropenic attack was significantly higher in G-CSF group than of the HDMP group. Especially in patients experiencing frequent neutropenic attacks and hence interruptions of the therapy, one of the myelopoiesis induction therapies can be used to shorten the duration of neutropenia. For this indication short-course HDMP therapy can be considered as an alternative to G-CSF in this patients due to its relatively low cost, amenability to outpatient administration, and well-tolerability by children.

Ulcerating molluscum contagiosum in a boy with relapsed acute lymphoblastic leukemia.

Molluscum contagiosum is an infectious disease presenting with flesh-colored, dome-shaped, umblicated papules. A few atypical presentations have been reported in immunodeficient patients. A 5-year-old boy with acute lymphoblastic leukemia, presented with bright white-colored papular lesions with no umblications on the chin during his continuation chemotherapy. Increased number of the lesions covered almost his entire chin in months. Topical therapies did not improve the lesions. After his bone marrow relapse, induction chemotherapy was withheld because of bronchopneumonia after febrile neutropenia. After initiation of a combination of systemic parenteral antibiotic and antifungal therapies, his parents squeezed one of his papular lesions. Meanwhile, systemic acyclovir was added to his therapy, because of herpes labialis. Despite the large spectrum of his therapies, in 1.5 months, this small lesion progressed to a large lesion with erythematous ground and a central ulceration. Etiology of the lesion could not be enlightened until a skin biopsy that was compatible with the molluscum contagiosum. A partial resolution was achieved by cryotherapy. In conclusion, molluscum contagiosum may present as an ulcerating lesion during childhood leukemia treatment. A skin biopsy should be performed for the accurate diagnosis of atypical cutaneous lesions in immunocompromised patients.

Cardiac involvement in an adolescent with acute lymphoblastic leukemia.

Cardiac complications of the pediatric patients with acute leukemia are common. Most of the cardiac complications may be due to chemotherapeutics such as antracyclins, besides anemia, infections, or direct leukemic infiltrations of the heart. It is reported that leukemic infiltration is frequent in the postmortem examination of the myocardium and pericardium. However, at the antemortem examination, pericardial involvement is rare and there is no myocardial involvement reported at the time of diagnosis in patients with acute leukemia in the English literature. Here, the authors report an adolescent with acute lymphoblastic leukemia who had myocardial infiltration at the time of diagnosis.

Acute renal failure with acyclovir treatment in a child with leukemia.

Acyclovir is an effective, frequently used antiviral agent. Adverse effects of this drug are well known and are especially seen with high doses and/or dehydration. In this article, we report a 6-year-old boy with leukemia with nonoliguric acute renal failure in normal hydration status after using acyclovir treatment. He had no preexisting renal impairment, and there were no additional symptoms. Dimercaptosuccinic acid radionucleid scyntigraphy and other laboratory findings revealed impairment of proximal tubule function, in addition to distal tubule. We emphasize that renal functions should be monitored carefully during treatment with acyclovir, and asymptomatic nephrotoxicity must be kept in mind.

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.

Delayed recognition of intrathecal methotrexate overdose.

A 10-year-old girl who presented to our hospital was diagnosed as having B-precursor cell acute lymphoblastic leukemia. St Jude's Total XIII protocol was started. In the second block of the consolidation phase, 10 hours after triple intrathecal treatment, we realized that instead of 12 mg, 120 mg of methotrexate had accidentally been given. Although the patient had no symptoms 10 hours after intrathecal treatment, to prevent the possible neurotoxic effects of methotrexate, a cerebrospinal fluid exchange was performed. Simultaneously, systemic dexamethasone and calcium folinic acid were given. At the time of this writing (2 y), the patient has had no symptoms and has continued on the chemotherapy protocol as planned. Administration of high-dose intrathecal methotrexate may not lead to symptoms, as was the case in our patient. This may be related to individual variations in cerebrospinal fluid dynamics and drug metabolism.

Incidence of and risk factors for childhood thrombosis: a single-center experience in Ankara, Turkey.

This study was conducted to analyze the incidence of and risk for thrombosis in thrombotic children monitored in the Department of Pediatric Hematology of our hospital at the time of diagnosis, in addition to the clinical characteristics of those patients. The clinical and laboratory findings of 122 patients diagnosed with thrombosis from 1997 to 2006 were retrospectively analyzed. The incidence of thrombosis was 88.6/10,000 hospital admissions. The authors found that 31.1% of the patients studied had a thrombosis in more than 1 region. The incidence of thrombosis by anatomic site was as follows: 42 thromboses in the peripheral arterial system, 39 in an intracardiac region, 38 in the abdominal venous system, 36 in the deep peripheral venous system, and 28 in the cerebral vascular system. The mean age of the patients at the time of diagnosis was 4.9 years. Of the patients studied, 10.7% were neonates, 35.3% were infants younger than 1 year, and 48.4% were younger than 2 years. Most of the patients had a congenital cardiac disease and spontaneous thrombosis, and 66.1% had at least 1 acquired risk factor, the most common of which were having undergone surgery (42%) or wearing a central venous catheter (39%). A hereditary factor for the development of thrombosis was present in 54% of the patients. The most frequently observed hereditary risk factor was the MTHFR 677C-T mutation, and the second most common was the factor V Leiden mutation. Thrombosis should be considered a systemic disorder, and thrombotic patients should be evaluated with appropriate methods. Acquired and hereditary risk factors should be analyzed systematically in thrombotic patients.

Bone fracture: an unusual presentation of acute megakaryoblastic leukemia.

Some clinical manifestations of acute leukemia in children can mimic orthopedic conditions, and t is variable presentation often makes diagnosis difficult. Bone changes in leukemia are well documented, but there are only a few accounts of children with acute leukemia who present with bone fractures. This report describes a case of this rare combination in a very young boy who presented with fractures of both proximal humerus and left proximal femur and massive periosteal reactions of both humerus and femur and also cystic lesions of proximal femur and iliac bone accompanying aggressive acute megakaryoblastic leukemia.

The role of splenectomy in children with juvenile myelomonocytic leukemia.

Splenectomy has been performed as a palliative treatment both in adults and children with myelodysplastic syndrome (MDS). However, there is no report describing the course after splenectomy in children with MDS. The aim of this study was to evaluate the impact of splenectomy on the outcome of six children with juvenile myelomonocytic leukemia (JMML) who had no HLA identical donor and who became unresponsive to chemotherapy. Persistent thrombocytopenia, increased erythrocyte transfusion requirement and massive splenomegaly were the indications for splenectomy. Hemoglobin values and platelet counts improved following splenectomy in five out of the six patients. Erythrocyte transfusion requirements decreased and none of the patients who responded received erythrocyte transfusion for at least six months. More importantly, the quality of life improved markedly. No mortality related to splenectomy was observed. In conclusion, splenectomy may be considered as a safe supportive treatment approach for some children with JMML.

Anti-D immunoglobulin-induced prolonged intravascular hemolysis and neutropenia.

Intravenous anti-D immunoglobulin (anti-D IVIG) is indicated for the treatment of immune thrombocytopenic purpura (ITP) in nonsplenectomized patients who are Rh(D)-positive. Recent reports have described episodes of intravascular hemolysis after anti-D IVIG. We report an adolescent boy with chronic ITP who required multiple transfusions of erythrocyte suspensions when intravascular hemolysis persisted for 6 months after anti-D IVIG treatment. He did not have hemolytic anemia before treatment. The features of our case suggest that pediatric patients treated with anti-D IVIG for ITP should be closely monitored for signs and symptoms of hemoglobinemia and/or hemoglobinuria, and clinically significant anemia. Our case proposes that persistence of immune hemolysis after this treatment may be related to presence of previously defined predisposing agents like tuberculosis and antituberculous therapy. Our observations suggest that steroid therapy can be effective in patients who developed prolonged hemolytic anemia and neutropenia after anti-D IVIG therapy.

Hydrops fetalis in a neonate with down syndrome, transient myeloproliferative disorder and hepatic fibrosis.

Transient myeloproliferative disorder is a self limiting disorder characterized by leukocytosis with the presence of megakaryoblasts in the peripheral blood and bone marrow, anemia, thrombocytopenia, and organomegaly. It occurs in approximately 10% of newborn infants with Down syndrome. Hepatic fibrosis is seen in the severe form of transient myeloproliferative disorder with Down syndrome that is characterized by diffuse intralobular sinusoidal fibrosis and extramedullary hematopoesis. We describe a patient with hydrops fetalis, Down syndrome, and transient myeloproliferative disorder. We suggest that patients with the severe form of transient myeloproliferative disorder should be examined for hepatic fibrosis.