With the purpose of assess the experience of off-pump hybrid approach for palliation of hypoplastic left heart syndrome 15 neonates included in the study. The mean diameter of the ascending aorta was 2.08 +/- 0.14mm. 6 (40 %) patients had concomitant large ventricular septum defect. Hybrid palliation surgery included bilateral banding of pulmonary artery branches to 2.5-3.5 mm in 15 patients, supplemented by endovascular stent implantation in the lumen of the patent ductus arteriosus in 15 patients; balloon atrial septostomy-in 6 (40 %) patients. In-hospital mortality comprised 60 % (n=9): 6 (66.7 %)-due to heart failure; 2 (22.2 %)-due to septic pneumonia; in 1 (11.1 %)-Rashkind procedure complicated with left atrium perforation. 4 (26.7 %) patients discharged with improvement. In neonates with extremely high risk of performing Norwood I-Blalock /Sano, the alternative is off-pump hybrid palliative intervention, serving like a life-supporting "bridge" either to Norwood-Glenn surgery, and/or subsequent heart transplantation.
Background The COVID-19 pandemic posed severe challenges to delivery of services at Primary Care level and for achieving follow-up of patients with chronic diseases.Objectives We analysed data from the PRICOV-19 study to explore determinants of active follow-up for chronic disease patients in seven Central and Eastern European (CEE) countries during the pandemic.Methods Pricov-19 was a cross-sectional study conducted within PC (Primary Care) practices in 37 European countries. We analysed data from 7 CEE countries (Bulgaria, Czech Republic, Hungary, Poland, Moldova, Romania, Ukraine) collected between November 2020 and December 2021. Practices were recruited through random or convenience sampling and participation of practices was voluntary. We performed descriptive statistics to identify the level of follow-up of chronic disease and what health system and practice-specific factors were associated with better follow-up. We used logistic regression and meta-analysis techniques to explore associations and heterogeneity between countries.Results 67.8% out of 978 practices reported actively following up chronic patients. Positive associations were found between active follow-up and such as having more GPs (aOR = 1.18, p-value = 0.005), an above-average chronic patient population (aOR = 3.13, p-value = 0.006), adequate government support (aOR = 2.35, p-value = 0.001), and GPs having time for guideline reading (aOR = 0.008, p-value = 1.71).Conclusions Patient follow-up, was influenced by different health system and practice-specific factors. The implications suggest the need for government support to enhance PC practice organisation during crises and solutions to decrease GP workload and provide tailored care for patients with chronic disease.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare disorders in childhood with a variable clinical presentation. Given ANCA vasculitides' rarity, data informing clinical practice and treatment are mainly based on adult data. The purpose of this study was to characterize clinical characteristics of ANCA-associated glomerulonephritis (AAGN) in childhood to determine factors associated with adverse renal outcome and the requirement for kidney replacement therapy (KRT) across a global study population. This was a retrospective cross-sectional international survey distributed through professional pediatric nephrology organizations from December 2019 to March 2020 intended to create a registry of children with AAGN to understand clinical practices. Through an online form, pediatric nephrologists entered demographic and clinical information on all children with AAGN in their center in de-identified fashion. All centers were required to obtain their own institutional ethics or governance approval. Inclusion criteria were patients under 20 years at presentation who were diagnosed with AAGN in 2000-2019 and had kidney involvement. Data elements that were collected included baseline demographic data, clinical features at presentation, treatment received (maintenance and induction), and data on 3 clinical outcomes: requirement for KRT, serum creatinine concentration (Scr), and death. Specifically, nephrologists were asked to report the peak Scr and any requirement for KRT in the first 3 months after presentation during the induction treatment period. Nephrologists were also asked to report on the need for KRT and vital status at last known follow-up. Further methodological details are in Item S1. Based on responses received from 114 different clinicians, 337 children from 41 different countries were included in the final analysis. Median duration between initial presentation and last known follow-up was 26 (IQR, 11-57) months. Table S1 details baseline characteristics of included children. Table S2 shows the organ involvement at presentation across different clinical phenotypes. Table 1 shows the most frequent induction and maintenance treatments used in the entire cohort. A total of 113 children (34%) received plasma exchange at induction. Sixteen deaths were reported in this cohort (5% mortality), with a mean age at death of 13.7 ±5.7 years.Table 1Main Combinations of Induction and Maintenance Treatment in Entire AAGN CohortMain Treatment CombinationsValueInductionSteroids,aIntravenous or oral. cyclophosphamide100 (30%)Steroids,aIntravenous or oral. cyclophosphamide, PE (± IVIG)56 (17%)Steroids,aIntravenous or oral. rituximab25 (7%)SteroidsaIntravenous or oral.22 (7%)Steroids,aIntravenous or oral. cyclophosphamide, rituximab, PE (± IVIG)21 (6%)Steroids,aIntravenous or oral. mycophenolate mofetil13 (4%)Other combinations96 (28%)None4 (1%)MaintenanceMycophenolate mofetil and steroids100 (31%)Azathioprine and steroids49 (15%)Cyclophosphamide and steroids25 (8%)Steroids20 (6%)Steroids and rituximab19 (6%)Azathioprine17 (5%)Mycophenolate mofetil8 (2%)Rituximab8 (2%)Other combinations62 (19%)None15 (5%)Induction therapy information was available from all 337 patients, maintenance treatment data from 327 patients. "Other combinations" refers to multiple different combinations used less commonly. Abbreviations: IVIG, intravenous immunoglobulin; PE, plasma exchange.a Intravenous or oral. Open table in a new tab Induction therapy information was available from all 337 patients, maintenance treatment data from 327 patients. "Other combinations" refers to multiple different combinations used less commonly. Abbreviations: IVIG, intravenous immunoglobulin; PE, plasma exchange. Table 2 characterizes the clinical factors and treatment according to KRT requirements at initial presentation and at last known follow-up. We found a high prevalence of adverse renal outcomes, with 40% of children requiring KRT at last known follow-up, slightly higher than previously published data.1Calatroni M. Consonni F. Allinovi M. et al.Prognostic factors and long-term outcome with ANCA-associated kidney vasculitis in childhood.Clin J Am Soc Nephrol. 2021; 16: 1043-1051https://doi.org/10.2215/CJN.19181220Crossref PubMed Scopus (8) Google Scholar, 2Özçelik G. Sönmez H.E. Şahin S. et al.Clinical and histopathological prognostic factors affecting the renal outcomes in childhood ANCA-associated vasculitis.Pediatr Nephrol. 2019; 34: 847-854https://doi.org/10.1007/s00467-018-4162-5Crossref PubMed Scopus (8) Google Scholar, 3Morishita K.A. Moorthy L.N. Lubieniecka J.M. et al.Early outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis.Arthritis Rheumatol. 2017; 69: 1470-1479https://doi.org/10.1002/art.40112Crossref PubMed Scopus (39) Google Scholar, 4Sacri A.-S. Chambaraud T. Ranchin B. et al.Clinical characteristics and outcomes of childhood-onset ANCA-associated vasculitis: a French nationwide study.Nephrol Dial Transplant. 2015; 30: i104-i112https://doi.org/10.1093/ndt/gfv011Crossref PubMed Scopus (70) Google Scholar Children who did (vs did not) require KRT at last known follow-up had a higher peak Scr during the first 3 months after their initial presentation. There was a higher proportion of girls and a higher proportion of myeloperoxidase-ANCA positivity in children who required KRT at last known follow-up, compared to those who did not require KRT. We note that children who required KRT at last known follow-up were more likely to have received plasma exchange as induction treatment, but this may simply be because children with more severe kidney involvement at presentation were more likely to be treated with plasma exchange. We note that mycophenolate mofetil was used more commonly as maintenance treatment for children compared to azathioprine, which differs from suggestions in the adult literature.5Hiemstra T.F. Walsh M. Mahr A. et al.Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial.JAMA. 2010; 304: 2381-2388https://doi.org/10.1001/jama.2010.1658Crossref PubMed Scopus (468) Google ScholarTable 2Clinical Variables and the Requirement for KRT During the First 3 Months After Initial Presentation and Last Known Follow-up in 326 Children With AAGNRequired KRT at Initial PresentationRequired KRT at Last Known Follow-upYesNoYesNoNo. of patients119207132194Female sex75%69%78%68%Age at presentation, y12.1 ± 4.412.5 ± 5.411.9 ± 4.612.7 ± 5.3MPO-ANCA71%64%77%60%High-income GDP61%66%58%68%Peak Scr during initial presentation, μmol/L736 ± 345173 ± 121616 ± 333218 ± 115Organ involvement at presentation Respiratory tract50%42%50%41% Ear, nose, and throat12%17%10%19% Skin13%32%17%30% Musculoskeletal9%24%18%19% Neurological16%8%18%6% Eye5%10%7%9%Induction treatment IV steroids95%80%92%81% Rituximab29%27%25%29% IV cyclophosphamide55%57%64%56% Plasma exchange57%19%44%26%Maintenance treatment Azathioprine22%27%24%27% Mycophenolate mofetil46%45%43%47% Rituximab17%17%14%19%Continuous variables given as mean ± SD. Follow-up on the need for KRT was not available on 11 children; therefore data on 326 children are presented in this table. Conversion factor for Scr μmol/L to mg/dL, ×0.0113. Abbreviations: GDP, gross domestic product; IV, intravenous; MPO, myeloperoxidase. Open table in a new tab Continuous variables given as mean ± SD. Follow-up on the need for KRT was not available on 11 children; therefore data on 326 children are presented in this table. Conversion factor for Scr μmol/L to mg/dL, ×0.0113. Abbreviations: GDP, gross domestic product; IV, intravenous; MPO, myeloperoxidase. This study is unique, as it was conducted across 41 countries, giving a broad cross-sectional assessment of demographics and baseline characteristics of children affected by AAGN. Potential limitations of this study include an over-representation of children with severe renal outcomes, given the collection of data through a survey of pediatric nephrologists; but this is also a strength, as this study focuses on the subgroup of children with ANCA vasculitis who have kidney involvement. Data were only available at disease presentation and latest follow-up, which limits our ability to comment on kidney function over time. In addition, we did not collect data on histology, meaning that the diagnosis of AAGN was clinical rather than histological and we had limited ability to relate histology to clinical outcomes. We also do not have data on proteinuria at presentation, which is a further limitation. In conclusion, this large international cohort of children with AAGN demonstrates the high risk of chronic kidney disease and requirement for KRT in this population. Designed the study, collected and collated data, conducted and reviewed analyses: MM, TW, NP, FS, MV, KT; devised the statistical analysis plan, conducted statistical analyses: DK, RK, LS; reviewed patients for inclusion, collected data: MA, IA, AA, JB, RB, BB, ZB, OB, EY-hC, DC, SD, ED, MD-D, LAE, LE, VF, HF, JF-D, AG, VG, MLG, MHansen, MHattori, XH, NH, DI, HGK, VK, IK, AL, SM, AMaxted, AMoczulska, RM, TN, MP, CP, IP, CS-K, SS, RSchild, MS, RSinha, APS, MStack, MSzczepanska, AT, JT, VU, CZ, JZ. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. This study has been supported by the European Rare Kidney Disease Network (ERKNet). ERKNet is co-funded by the European Union within the framework of the Third Health Programme "ERN-2016 - Framework Partnership Agreement 2017-2021." The funders had no role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication. The authors declare that they have no relevant financial interests. We are grateful to the European Society of Paediatric Nephrology (ESPN) and the International Paediatric Nephrology Association (IPNA) for their support in administering this study. We are grateful to all colleagues and pediatric nephrology centers contributing cases to this study. Aspects of this work were presented in abstract form at the 53rd ESPN Annual Meeting held in Amsterdam, The Netherlands, in September 2021. Received February 11, 2022. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form May 18, 2022. Download .pdf (.29 MB) Help with pdf files Supplementary File (PDF)Item S1; Tables S1, S2.
IntroductionGrowing evidence supports the effectiveness of fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), although its effects seem to depend on the method of introduction, the number of procedures, the donor material, and the severity of UC.AimThis study aimed to assess FMT's clinical and microbiological efficacy, tolerability, and safety in patients with mild-to-moderate UC.Material and methodsPatients with mild-to-moderate UC were randomized into two groups. The first group (standard-care, n = 27) was treated with basic therapy–mesalazine–at a daily dose of 3 g (2 g orally + 1 g rectally). In the second group (FMT group, n = 26), while taking mesalazine at the indicated dose, each patient with UC as add-on therapy underwent a single FMT procedure with fresh material delivered by colonoscopy from a healthy donor. The clinical efficacy of treatment in both groups was evaluated after 4 and 8 weeks. The primary outcome was remission of UC, defined as a partial Mayo score ≤2, and decreased fecal calprotectin. All patients underwent bacteriological examination of feces for quantitative microbiota composition changes.ResultsClinical response in the form of a significant decrease in stool frequency and a tendency to normalize its consistency after 4 weeks was detected in 14 (51.9%) patients of the standard care group and 16 patients (61.5%) of the FMT group (p = 0.583). The Mayo score in the standard care group was 3.59 ± 1.21 and in the FMT group−3.15±1.04 (p=0.166). After 8 weeks, the main primary endpoint was achieved in 70.4% of the standard-care group patients as compared to 84.6% of participants who received FMT as add-on therapy (p = 0.215). A more pronounced decrease in Mayo score was observed in the FMT group compared to the standard-care group (1.34 ± 1.44 vs. 2.14 ± 1.4; p = 0.045). All patients also showed a significant decrease in fecal calprotectin levels, which correlated with clinical data, stool frequency, and clinical remission. An improvement in gut microbiota composition was noted in both groups, albeit it was significantly more pronounced in the FMT group.ConclusionsFTM in patients with mild-to-moderate UC is a well-tolerated, effective, and safe method of treatment in comparison to basic therapy.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05538026?term=kobyliak&draw=2&rank=4, identifier: NCT05538026.
BACKGROUND Recent advances in the treatment of breast cancer (BC) have been related to the personalization of therapy. The methylation status of the promoter regions of tumor suppressor genes such as BRCA1 and BRCA2 is supposed to be useful as a prognostic factor in BC patients. AIM To investigate the frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes in tumor tissue of BC patients, and the relation of hypermethylation to the clinical course of the disease. MATERIALS AND METHODS Molecular genetic studies were performed on 50 BC tissue samples in order to determine the methylation status of the promoter regions of the BRCA1 and BRCA2 genes. RESULTS Hypermethylation of the BRCA1 promoter region was detected in 34% of BC cases, hypermethylation of the BRCA2 promoter region - in 50% of cases, and hypermethylation of the promoter region of both genes - in 20% of cases. A significant increase in the incidence of hypermethylation of the BRCA2 promoter region was found in the group of patients older than 56 years, mainly in patients with triple-negative breast cancer and without family history of BC. CONCLUSIONS The high frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes, as well as their co-methylation in tumor tissue of BC patients has been detected.
