Search

Background: Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than 1 year. Oncolytic viral therapy has been evaluated in patients with pediatric gliomas elsewhere in the brain, but data regarding oncolytic viral therapy in patients with DIPG are lacking. Methods: We conducted a single-center, dose-escalation study of DNX-2401, an oncolytic adenovirus that selectively replicates in tumor cells, in patients with newly diagnosed DIPG. The patients received a single virus infusion through a catheter placed in the cerebellar peduncle, followed by radiotherapy. The primary objective was to assess the safety and adverse-event profile of DNX-2401. The secondary objectives were to evaluate the effect of DNX-2401 on overall survival and quality of life, to determine the percentage of patients who have an objective response, and to collect tumor-biopsy and peripheral-blood samples for correlative studies of the molecular features of DIPG and antitumor immune responses. Results: A total of 12 patients, 3 to 18 years of age, with newly diagnosed DIPG received 1×1010 (the first 4 patients) or 5×1010 (the subsequent 8 patients) viral particles of DNX-2401, and 11 received subsequent radiotherapy. Adverse events among the patients included headache, nausea, vomiting, and fatigue. Hemiparesis and tetraparesis developed in 1 patient each. Over a median follow-up of 17.8 months (range, 5.9 to 33.5), a reduction in tumor size, as assessed on magnetic resonance imaging, was reported in 9 patients, a partial response in 3 patients, and stable disease in 8 patients. The median survival was 17.8 months. Two patients were alive at the time of preparation of the current report, 1 of whom was free of tumor progression at 38 months. Examination of a tumor sample obtained during autopsy from 1 patient and peripheral-blood studies revealed alteration of the tumor microenvironment and T-cell repertoire. Conclusions: Intratumoral infusion of oncolytic virus DNX-2401 followed by radiotherapy in pediatric patients with DIPG resulted in changes in T-cell activity and a reduction in or stabilization of tumor size in some patients but was associated with adverse events. (Funded by the European Research Council under the European Union's Horizon 2020 Research and Innovation Program and others; EudraCT number, 2016-001577-33; ClinicalTrials.gov number, NCT03178032.).

INTRODUCTION: Physiologic and pathophysiologic inflammation is mediated, at least in part, by the generation and release of reactive oxygen species into the local tissue milieu. The chronic inflammation observed in patients with inflammatory bowel disease (IBD) is thought to begin in the lining of the intestine and may progress to involve the entire bowel wall.In an effort to assess disease activity, clinicians rely on costly and technically invasive procedures such as colonoscopies. As such, there is currently a need for the development of less invasive and more cost-effective methods for use in the diagnosis and interval assessment of children and adults with these chronic intestinal inflammatory disorders. OBJECTIVES: The objective of this study was to first determine if ambient redox status can be reliably measured in the stool of patients with IBD. A second aim of the study was to determine if ambient stool redox status was related to underlying diagnosis, clinical disease activity, or response to therapy in patients with IBD . METHODS: We first our ability to measure redox redox standards using three different commercially available devices. Once demonstrated, we then the process of performing sample analysis under various conditions (room tempererture, refrigerated, frozen, or spun/unspun) to determine the conditions under which we were able to achieve the most stable redox assessments. Finally, we conducted a small pilot cohort study in hospitalized pediatric patients with IBD to assess if stool redox status informed about disease activityWe collected stool samples from seven patients admitted to the inpatient gastrointestinal service at Boston Children’s Hospital during a period extending from November of 2018 to March of 2019. RESULTS: Preliminary studies confirmed our ability to accurately measure relative redox status (RRS) using three different apparatuses. Furthermore, we were able to generate dilution curves using juices known to include oxidants, with linear regression r2 values of 0.99. In our patient population, we confirmed our ability to generate a reliable readings and consistent RRS measurements over. Frozen samples displayed less stable and higher RRS than those either refrigerated or kept at room temperature for up to 8-hours. This suggests that freeze-thaw cycles may impact adversely on the stability of oxidants and antioxidants in our samples. The RRS measurements from stool samples collected from patients who were exhibiting active symptoms of their IBD measured about -400 mV, while samples collected from hospitalized patients without IBD manifest RRS readings of about 100 mV. CONCLUSION: This preliminary study demonstrates our ability to measure RRS in the stool of patients with and without IBD. The stability we observed in samples that were either stored at room temperature or refrigerated demonstrated that these represented optimal storage options. Additionally, measurements from homogenized stool samples appeared to be more variable when compared to the relatively smaller range from centrifuged samples. Initial studies indicated a strong difference in RRS measurements between patients with inflammatory and non-inflammatory GI disease or inactive IBD. This difference suggests that measurements of RRS could provide a quantitative real-time assessments of disease activity and response to therapy in patients with IBD.

The present study involved the analyses of the Texas Medicaid prescription claims data. The population studied was made up of subjects between 10 and 18 years who had at least 2 prescriptions of the same oral antidiabetic (OAD) medication from January 1, 2006 through December 31, 2009. Twelve months’ data for each subject were analyzed. The main aim of the study was to describe OAD medication use patterns in the study population, assess trends in Medication Possession Ratio (MPR) and persistence in the study population and determine the relationship between age and MPR and between age and persistence while controlling for covariates. Results of the descriptive statistics, multiple and logistic regression analyses are reported. The average age (± SD) of the 3,109 eligible subjects was 14 (± 2) years; minority populations made up the majority (87%) of the population; 67% of the population were females; and 91% were on the OAD metformin. The overall mean MPR (± SD) for the population was 45% (± 27). A significant negative relationship between MPR and age was reported while controlling for covariates (p= 80%), logistic regression analysis also found that age was significantly and negatively related to MPR (p < 0.0001). In addition, the white race and male were again significantly related to a higher level of adherence, holding other variables constant. The overall mean days to non-persistence (± SD) was 108 days (± 86). Persistence was significantly and negatively associated with age, holding other variables constant (p < 0.0001). Among the covariates, white race was significantly related to longer persistence. In conclusion, adherence and persistence are generally low in the study population. Age, gender and race were significantly associated with adherence. Being younger, male, and white were significantly associated with a higher level of adherence, while being younger and white were significantly associated with longer persistence. Healthcare providers therefore need to intensify efforts to improve adherence in pediatric patients especially those at the brink of adulthood.

The present study involved the analyses of the Texas Medicaid prescription claims data. The population studied was made up of subjects between 10 and 18 years who had at least 2 prescriptions of the same oral antidiabetic (OAD) medication from January 1, 2006 through December 31, 2009. Twelve months’ data for each subject were analyzed. The main aim of the study was to describe OAD medication use patterns in the study population, assess trends in Medication Possession Ratio (MPR) and persistence in the study population and determine the relationship between age and MPR and between age and persistence while controlling for covariates. Results of the descriptive statistics, multiple and logistic regression analyses are reported. The average age (± SD) of the 3,109 eligible subjects was 14 (± 2) years; minority populations made up the majority (87%) of the population; 67% of the population were females; and 91% were on the OAD metformin. The overall mean MPR (± SD) for the population was 45% (± 27). A significant negative relationship between MPR and age was reported while controlling for covariates (p= 80%), logistic regression analysis also found that age was significantly and negatively related to MPR (p < 0.0001). In addition, the white race and male were again significantly related to a higher level of adherence, holding other variables constant. The overall mean days to non-persistence (± SD) was 108 days (± 86). Persistence was significantly and negatively associated with age, holding other variables constant (p < 0.0001). Among the covariates, white race was significantly related to longer persistence. In conclusion, adherence and persistence are generally low in the study population. Age, gender and race were significantly associated with adherence. Being younger, male, and white were significantly associated with a higher level of adherence, while being younger and white were significantly associated with longer persistence. Healthcare providers therefore need to intensify efforts to improve adherence in pediatric patients especially those at the brink of adulthood.

Oxidative stress is associated with cancers via many mechanisms including lipid peroxidation and DNA damage. The interest in research on the role of free radicals in cancer pathogenesis is increasing. Acute lymphoblastic leukemia (ALL), the most common childhood cancer, is the primary cause of cancer-related mortality in children. Many components given to treat leukemia are associated with free radical production. In addition, the properties of antioxidant compounds for protection and alleviation of side effects of chemotherapy have been reported. However, there are a few reports on oxidative stress and antioxidant status in children with ALL. Therefore, we reviewed this topic for scientific knowledge and future research.

Realizamos una exposición de nuestra casuística, en un periodo comprendido desde 1972 hasta 1991, presentando 22 pacientes con esclerosis tuberosa. Al mismo tiempo realizamos una revisión de la literatura nacional e internacional sobre el tema, destacando sus aspectos epidemiológicos, clínicos, radiológicos, genéticos, diagnósticos, terapéuticos y pronósticos.

วัตถุประสงค์: เพื่อเปรียบเทียบผลวิธีการสอนช่วยชีวิตขั้นพื้นฐาน ระหว่างวิธีการสอนด้วยวีดิทัศน์และฝึกปฏิบัติกับพยาบาล และวิธีการสอนและฝึกปฏิบัติด้วยพยาบาล ต่อความรู้และการปฏิบัติในการช่วยชีวิตเด็กขั้นพื้นฐาน ของผู้ดูแลผู้ป่วยเด็กที่เสี่ยงต่อการเกิดภาวะหัวใจหยุดเต้น รูปแบบการวิจัย: การวิจัยเชิงทดลอง วิธีดำเนินการวิจัย: กลุ่มตัวอย่างเป็นผู้ดูแลหลักของผู้ป่วยเด็กที่เสี่ยงต่อการเกิดภาวะหัวใจหยุดเต้นในโรงพยาบาลศิริราช จำนวน 98 คน เก็บข้อมูลโดยใช้แบบสัมภาษณ์ข้อมูลทั่วไป แบบประเมินความรู้ และแบบประเมินการปฏิบัติในการช่วยชีวิตเด็กขั้นพื้นฐาน วิเคราะห์ข้อมูลโดยใช้สถิติเชิงพรรณนา การทดสอบแมน-วิทนีย์ ยู การทดสอบไคร์สแควร์ และการทดสอบฟิชเชอร์ ผลการวิจัย: ผู้ดูแลผู้ป่วยเด็กกลุ่มที่สอนด้วยวีดิทัศน์และฝึกปฏิบัติกับพยาบาลมีคะแนนรวมเฉลี่ยหลังเรียน และการปฏิบัติในภาพรวมของการช่วยชีวิตเด็กขั้นพื้นฐาน ไม่แตกต่างจากกลุ่มที่สอนและฝึกปฏิบัติด้วยพยาบาลอย่างมีนัยสำคัญ .05 (p > .05) แต่ใช้ระยะเวลาที่พยาบาลต้องสอนน้อยกว่ากลุ่มที่สอนและฝึกปฏิบัติโดยพยาบาลอย่างมีนัยสำคัญทางสถิติ (Z = -7.43, p < .05) สรุปและข้อเสนอแนะ: วิธีการสอนเพื่อให้ความรู้และทักษะการปฏิบัติในการช่วยชีวิตเด็กขั้นพื้นฐานแก่ผู้ดูแล ไม่ว่าจะใช้วิธีสอนด้วยวีดิทัศน์และฝึกปฏิบัติกับพยาบาลหรือวิธีสอนโดยพยาบาลให้ผลไม่แตกต่างกัน ดังนั้น จึงควรสนับสนุนให้นำวิธีการสอนด้วยวีดิทัศน์และฝึกปฏิบัติกับพยาบาลมาใช้ในทางปฏิบัติเนื่องจากวิธีนี้ใช้เวลาของพยาบาลน้อยกว่า ยิ่งกว่านั้นควรให้วีดิทัศน์แก่ผู้ดูแลนำกลับไปทบทวนที่บ้านเพื่อให้ทักษะการช่วยเหลือคงทน