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The histologic fetal inflammatory response and neonatal outcomes: systematic review and meta-analysis.
Kovács, K, Kovács, ŐZ, Bajzát, D, Imrei, M, Nagy, R, Németh, D, Kói, T, Szabó, M, Fintha, A, Hegyi, P, et al
American journal of obstetrics and gynecology. 2023
Abstract
OBJECTIVE This study aimed to investigate the prognostic role of concomitant histological fetal inflammatory response with chorioamnionitis on neonatal outcomes through a systematic review and meta-analysis of existing literature. DATA SOURCES The primary search was conducted on October 17, 2021, and it was updated on May 26, 2023, across 4 separate databases (MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and Scopus) without using any filters. STUDY ELIGIBILITY CRITERIA Observational studies reporting obstetrical and neonatal outcomes of infant-mother dyads with histological chorioamnionitis and histological fetal inflammatory response vs infant-mother dyads with histological chorioamnionitis alone were eligible. Studies that enrolled only preterm neonates, studies on neonates born before 37 weeks of gestation, or studies on neonates with very low birthweight (birthweight <1500 g) were included. The protocol was registered with the International Prospective Register of Systematic Reviews (registration number: CRD42021283448). METHODS The records were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random-effect model-based pooled odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes. RESULTS Overall, 50 studies were identified. A quantitative analysis of 14 outcomes was performed. Subgroup analysis using the mean gestational age of the studies was performed, and a cutoff of 28 weeks of gestation was implemented. Among neonates with lower gestational ages, early-onset sepsis (pooled odds ratio, 2.23; 95% confidence interval, 1.76-2.84) and bronchopulmonary dysplasia (pooled odds ratio, 1.30; 95% confidence interval, 1.02-1.66) were associated with histological fetal inflammatory response. Our analysis showed that preterm neonates with a concomitant histological fetal inflammatory response are more likely to develop intraventricular hemorrhage (pooled odds ratio, 1.54; 95% confidence interval, 1.18-2.02) and retinopathy of prematurity (pooled odds ratio, 1.37; 95% confidence interval, 1.03-1.82). The odds of clinical chorioamnionitis were almost 3-fold higher among infant-mother dyads with histological fetal inflammatory response than among infant-mother dyads with histological chorioamnionitis alone (pooled odds ratio, 2.99; 95% confidence interval, 1.96-4.55). CONCLUSION This study investigated multiple neonatal outcomes and found association in the case of 4 major morbidities: early-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, and retinopathy of prematurity.
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Immunohistochemical Detection of the Presence of Vitamin D Receptor in Childhood Solid Tumors.
Juhász, O, Jákob, N, Rajnai, H, Imrei, M, Garami, M
Cancers. 2022;(14)
Abstract
Background: Our previous work has shown a correlation between lower vitamin D levels in children with cancer and adverse prognosis. It suggests that supplying vitamin D is reasonable. VDR expression in childhood solid tumors has been linked to tumor characteristics and patient survival in only a few studies. Methods: For this study, 177 children with solid tumors were selected whose biopsies and tumor tissue formalin-fixed, paraffin-embedded tissue blocks were available for immunohistochemical analysis at Semmelweis University, Budapest (Hungary). Results: We found that non-significant VDR expression was associated with a significantly less favorable prognosis (p = 0.0061) in the examined childhood solid tumors. There was a clinically significant association; non-significant VDR expression had more than 14-fold odds of an unfavorable prognosis (OR = 14.74). The rate of VDR expression differed significantly between tumor types (p < 0.0001). Conclusion: In conclusion, VDR expression measured by IHC staining is inversely associated with aggressive characteristics in different childhood cancers. The downregulation of VDR expression in more aggressive childhood cancers suggests that functional vitamin D activity may slow or block cancer progression.
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Examining the Vitamin D Status of Children With Solid Tumors.
Juhász, O, Jakab, Z, Szabó, A, Garami, M
Journal of the American College of Nutrition. 2020;39(2):128-134
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Plain language summary
Literature shows that 75% of the adult population worldwide experience vitamin D deficiency, of whom 13% fall under the category of extremely severe vitamin D deficiency (<10 ng/ml). The aim of this retrospective study was to compare the Vitamin D status of children with tumours or without. A secondary aim was to analyse the effects of vitamin D supplementation (as a complement to cancer treatment) on the vitamin D levels of children. The study included 173 children (males n=96; females n=77) aged between 0 and 18 who were treated for cancer. The control group consisted of 569 (males n=310; females n=259) children, aged 0 to 4 who received treatment at the clinic for reasons other than cancer. Results indicate that initial Vitamin D levels were significantly lower among children with cancer (19% lower than in the control group). A correlation between insufficient and deficient initial serum vitamin D levels and unfavourable prognosis was found. Authors suggest that vitamin D supplementation would be most efficient if medicine would follow the present trend of personalised therapy.
Abstract
Objective: Our aims were to compare the vitamin D status of children with and without cancer and to examine the possible correlation between vitamin D levels in children with cancer before initiating treatment and prognosis.Method: We compared the data of 173 children with cancer with those of 569 children without cancer.Results: We measured a significant difference (p = 1.34E-08) between the vitamin D levels of children with cancer before treatment and children without cancer. There was a significant correlation between the initial vitamin D levels of children with cancer and the prognosis (p = 0.016, odds ratio = 51.33) at 5% significance.Conclusions: The average vitamin D level was 19.76% lower in the population with cancer compared with the average of the control group, and we found a correlation between the lower vitamin D levels in children with cancer and the adverse prognosis. We suggest that supplying vitamin D is reasonable and a prospective study of vitamin D in pediatric patients with cancer is recommended.
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Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain-specific DNMT3B isoform in the embryonal brain tumor ETMR.
Kleinman, CL, Gerges, N, Papillon-Cavanagh, S, Sin-Chan, P, Pramatarova, A, Quang, DA, Adoue, V, Busche, S, Caron, M, Djambazian, H, et al
Nature genetics. 2014;(1):39-44
Abstract
Embryonal tumors with multilayered rosettes (ETMRs) are rare, deadly pediatric brain tumors characterized by high-level amplification of the microRNA cluster C19MC. We performed integrated genetic and epigenetic analyses of 12 ETMR samples and identified, in all cases, C19MC fusions to TTYH1 driving expression of the microRNAs. ETMR tumors, cell lines and xenografts showed a specific DNA methylation pattern distinct from those of other tumors and normal tissues. We detected extreme overexpression of a previously uncharacterized isoform of DNMT3B originating at an alternative promoter that is active only in the first weeks of neural tube development. Transcriptional and immunohistochemical analyses suggest that C19MC-dependent DNMT3B deregulation is mediated by RBL2, a known repressor of DNMT3B. Transfection with individual C19MC microRNAs resulted in DNMT3B upregulation and RBL2 downregulation in cultured cells. Our data suggest a potential oncogenic re-engagement of an early developmental program in ETMR via epigenetic alteration mediated by an embryonic, brain-specific DNMT3B isoform.
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Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in pediatric cancer patients.
Garami, M, Schuler, D, Babosa, M, Borgulya, G, Hauser, P, Müller, J, Paksy, A, Szabó, E, Hidvégi, M, Fekete, G
Journal of pediatric hematology/oncology. 2004;(10):631-5
Abstract
PURPOSE An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC. METHODS Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline). There were no significant differences in the average age of the patients, the length of treatment time (MSC) or follow-up, the number of patients with central venous catheters, the number of chemotherapy cycles, the frequency of preventive counterneutropenic interventions, or the type and dosage of antibiotic and antipyretic therapy used in the two groups. RESULTS During the treatment (follow-up) period, there was no progression of the malignant disease, whereas at end-point the number and frequency of febrile neutropenic events significantly differed between the two groups: 30 febrile neutropenic episodes (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed rank test, P < 0.05). CONCLUSIONS The continuous supplementation of anticancer therapies with the medical nutriment MSC helps to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers.