The Inhibitory Effects of Amylase and Streptokinase on Minimum Inhibitory Concentration of Antibiotics Used to Treat Gram Negative Bacteria Biofilm Infection on Indwelling Devices.

The study evaluated and compared the effect of adding streptokinase and amylase to antibiotics that are already used in clinical practice to treat Gram negative bacteria biofilm infection on indwelling devices on the antibiotics' minimum inhibitory concentration (MIC). 24 h-old biofilms were developed on 96-well plate with eight clinical isolates. MIC of amikacin, cefepime, ceftazidime, colistin, meropenem, and piperacillin-tazobactam, on biofilms were measured before and after the addition of 25 U/ml streptokinase and 25 µg/ml amylase with microplate reader. The addition of streptokinase reduces the MICs of cefepime, ceftazidime, colistin, meropenem from (16, 16, 8, 4 µg/ml) to (8, 1, 1, 0.5 µg/ml) in Escherichia coli (isolate 1). While the addition of amylase reduces the MICs of only cefepime, ceftazidime from (16, 16 µg/ml) to (2, 4 µg/ml) in E. coli (isolate 1). In Pseudomonas aeruginosa (isolate 4), the MICs of amikacin, cefepime, ceftazidime, colistin and meropenem (64, 16, 32, 4, 32 µg/ml) reduced to (2, 1, 0.5, 0.25, 0.5 µg/ml) with streptokinase and (4, 4, 4, 2, 0.5 µg/ml) with amylase respectively. Similar inhibitions were seen in Pseudomonas putida, Proteus mirabilis. We can conclude that the addition of streptokinase and amylase were effective in reducing the MICs of antibiotics that are commonly used to treat Gram negative bacteria biofilm infection on indwelling devices, thereby increasing susceptibility of bacteria to antibiotics. Streptokinase obviously had a greater effect than amylase, implying that it should be prioritized in future in vivo and clinical studies to obtain successful therapy with antibiotics on biofilm infections.

The effect of biofilm inhibitor N-acetylcysteine on the minimum inhibitory concentration of antibiotics used in Gram-negative bacteria in the biofilm developed on catheters.

The study determined the effect of N-acetylcysteine (NAC) on the susceptibility of various antibiotics used to treat Gram-negative catheter-related infection in isolates obtained from pediatric patients admitted to the hematology and oncology department of Medical Park Bahçelievler hospital in Istanbul, Turkey. Biofilms were created in vitro utilizing clinical isolates of Escherichia coli, Pseudomonas aeruginosa, Pseudomonas putida, and Proteus mirabilis. 24 h old biofilms were developed on 96-well plate with strains and the minimum biofilm inhibitory concentration (MBIC) of six antibiotics were measured before and after the addition of 75 mg/ml N-acetylcysteine with microplate reader at 450 nm after crystal violet assay. The addition of NAC reduce the MBIC of cefepime, ceftazidime, colistin, meropenem from (16, 16, 8, 4 µg/ml) to (8, 4, 4, 2 µg/ml) respectively in E. coli (isolate 1). In P. aeruginosa (isolate 4), the MBIC of amikacin, ceftazidime, meropenem (64, 32, and 32 µg/ml) reduced to (8, 1, and 0.5 µg/ml) respectively. MBIC of cefepime, colistin, meropenem (32, 16,and 16 µg/ml) reduced to (2, 2,and 0.5 µg/ml) respectively in P. putida (isolate 5). In P. mirabilis (isolate 6), MBIC of amikacin, cefepime, ceftazidime, colisitin and meropenem (64, 128, 32, 4, and 32 µg/ml) reduced to (8, 8, 1, 1, 4 µg/ml). NAC in combination therapy can practically reduce the MBIC of antibiotics used to treat Gram negative bacteria that develop biofilm in medical catheters. As a result, these combinations can be considered as an essential alternative for increasing the antibiotic susceptibility of pathogenic microorganisms and thus increasing treatment success rates.

Different Kinetics and Risk Factors for Isolated Extramedullary Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Leukemia.

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of post-transplantation mortality. Isolated extramedullary (EM) relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors, and outcome of iEMR compared with systemic relapse. The 5-year cumulative incidence of systemic relapse (either bone marrow [BM] only or BM combined with EMR) was 24.8%, and that of iEMR was 5.5%. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; P = .013). Complete response (CR) 2+/active disease at transplantation (hazard ratio [HR], 3.1; P < .001) and prior EM disease (HR, 2.3; P = .007) were independent risk factors for iEMR. Chronic graft-versus-host disease reduced the risk of systemic relapse (HR, 0.5; P = .043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% versus 15.3%; P = .089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, whereas those experiencing their iEMR at first relapse developed further systemic relapse and iEMR at approximately similar frequencies. A second iEMR was more common after a first iEMR than after a first systemic relapse (58.8% versus 13.0%; P = .001) and was associated with poor outcome. iEMR has a poor prognosis, particularly after a second relapse, and effective strategies are needed to improve outcomes.

Primary immunodeficiencies: HSCT experiences of a single center in Turkey.

BACKGROUND: Primary immunodeficiency diseases (PID) are characterized by the occurrence of frequent infections and are caused by many genetic defects. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for the majority of PID. As a Pediatric Hematology-Oncology-Immunology Transplantation Unit, we wanted to present our HSCT experience regarding treatment of primary immunodeficiency diseases. METHODS: 58 patients were included in the study between January 2014 and June 2019. We searched 9/10 or 10/10 matched-related donor (MRD) firstly, in the absence of fully matched-related donor. We screened matched unrelated donor (MUD) from donor banks. MRD was used in 24 (41.3%) patients, MUD in 20 (34.4%) patients, and haploidentical donors in 14 (24.1%) patients. Demographic data, HSCT characteristics, and outcome were evaluated. While 16 patients had severe combined immunodeficiency (SCID), the remaining was non-SCID. RESULTS: Of the 58 patients, 38 were male and 20 were female. Median age at transplantation was 12 months (range: 2.5-172 months). Combined immunodeficiencies consisted 67.2% of patients. Mean follow-up time was 27 months (6 months-5 years). Median neutrophil, lymphocyte, and thrombocyte engraftment days were similar in comparison of both donor type and stem cell source. The most common complication was acute GvHD in 15 (25.8%) patients. In total, five patients (31%) belonging to the SCID group and 10 patients (23.8%) belonging to the non-SCID group died. Our total mortality rate was 15 (25.8%) in all patients. CONCLUSIONS: We would like to present our HSCT experiences as a pediatric immunology transplantation center. Existing severe infections before transplantation period, BCGitis, and CMV are important issues of transplantation in Turkey. However, the follow-up time is shorter than some studies, our results regarding complications and survival are similar to previous reports.

Cross-sectional study: long term follow-up care for pediatric cancer survivors in a developing country, Turkey: current status, challenges, and future perspectives

Aim: The main purpose of this study is to determine the current status of long-term follow-up (LTFU) for childhood cancer survivors and the challenges of LTFU for pediatric cancer survivors at pediatric oncology institutions in Turkey. Material and methods: A questionnaire was e-mailed to the directors of 33 pediatric oncology centers (POCs) registered in the Turkish Pediatric Oncology Group (TPOG). Of these 33 active TPOG institutions, 21 participated in the study and returned their completed questionnaires. Results: Only 1 of the 21 participating centers had a separate LTFU clinic. The remaining centers provided LTFU care for childhood cancer survivors at the pediatric oncology outpatient clinic. Of these centers, 17 (80.9%) reported difficulty in transition from the pediatric clinic to the adult clinic, 14 (66.6%) reported insufficient care providers, and 12 (57.1%) reported insufficient time and transportation problems. As neglected late effects, 16 (76.1%) centers reported psychosocial and getty job problems and 11 (52.3%) reported sexual and cognitive problems. None of the centers had their own LTFU guidelines for their daily LTFU practice Conclusion: This study was the first to gain an overview of the needs of POCs and the gaps in survivorship services in Turkey. The results from this study will help to develop a national health care system and national guidelines for pediatric cancer survivors.

The Use of Allogeneic Mesenchymal Stem Cells in Childhood Steroid-Resistant Acute Graft-Versus-Host Disease: A Retrospective Study of a Single-Center Experience

Objective: Steroid-resistant acute graft-versus-host disease (srAGVHD) is the most important cause of morbidity and mortality after allogeneic stem cell transplantation. There are several treatment methods available, including mesenchymal stem cell (MSC) application. The aim of this study was to evaluate the results of MSC therapy performed in children with srAGVHD. Materials and Methods: MSC therapy was used in our center between November 2014 and December 2017 for 22 patients who developed srAGVHD. The patients were retrospectively evaluated in terms of treatment response and survival. Results: After application of MSCs, complete response was obtained in 45.5% of the subjects, partial response was obtained in 13.6%, and no response was obtained in 40.9%. We found that 45.5% of the patients were alive and 54.5% had died and our treatment results were similar to those in the literature. Response to MSC treatment was found to be the only prognostic marker affecting mortality. Conclusion: MSC application is a treatment method that can be used safely together with other treatment methods in srAGVHD, a condition that has a high mortality rate. There are almost no acute side effects. There are also no serious long-term side effects in the literature. Prospective randomized studies are required to obtain high-quality data.

An unusual case of neuroblastoma: a 17-year-old adolescent presented with bilateral diffuse lung metastasis at initial diagnosis.

Neuroblastoma (NB) is the most frequently diagnosed neoplasm during infancy and its incidence declines within the first 3-5 years of life. It can be rarely diagnosed in adolescents and young adults. Adolescents have advanced stage of disease, higher frequency of uncommon metastatic sites such as lungs, and worse outcomes. Herein, we describe an unusual case of NB in a 17-year-old adolescent presented with lung metastasis at diagnosis. The patient was diagnosed with stage IV NB. Thorax high-resolution computed tomography (HRCT) scan revealed irregular septal thickening with ground glass opacity consistent with pulmonary parenchymal metastases. After the first cycle of chemotherapy he developed pulmonary hemorrhage and respiratory distress. He required ventilation support and mechanical ventilation was started. Metastatic nodules were determined on second thorax HRCT. We lost the patient due to septic shock and multiple organ failure 2 months after diagnosis. In conclusion, adolescents with NB have unfavorable prognosis. These patients may have lung metastases at diagnosis. Therefore, detailed chest imaging at initial diagnosis is crucial.