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- Bonamy, AKE, et al.
(författare)
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Wide variation in severe neonatal morbidity among very preterm infants in European regions
- 2019
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Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 104:1, s. F36-F45
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates.DesignArea-based cohort study of all births before 32 weeks of gestational age.Setting16 regions in 11 European countries in 2011/2012.PatientsSurvivors to discharge from neonatal care (n=6422).Main outcome measuresSevere neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades ≥3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics.Results10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%–23.5%) and 13.8% including severe BPD (regional range 10.0%–23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%–18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P<0.001) and severe neonatal morbidity rates were not correlated with mortality rates (P=0.50).ConclusionSevere neonatal morbidity rates for VPT survivors varied widely across European regions and were independent of mortality rates.
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- Cuttini, M, et al.
(författare)
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Breastfeeding outcomes in European NICUs: impact of parental visiting policies
- 2019
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Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 104:2, s. F151-
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Tidskriftsartikel (refereegranskat)abstract
- The documented benefits of maternal milk for very preterm infants have raised interest in hospital policies that promote breastfeeding. We investigated the hypothesis that more liberal parental policies are associated with increased breastfeeding at discharge from the neonatal unit.DesignProspective area-based cohort study.SettingNeonatal intensive care units (NICUs) in 19 regions of 11 European countries.PatientsAll very preterm infants discharged alive in participating regions in 2011–2012 after spending >70% of their hospital stay in the same NICU (n=4407).Main outcome measuresWe assessed four feeding outcomes at hospital discharge: any and exclusive maternal milk feeding, independent of feeding method; any and exclusive direct breastfeeding, defined as sucking at the breast. We computed a neonatal unit Parental Presence Score (PPS) based on policies regarding parental visiting in the intensive care area (range 1–10, with higher values indicating more liberal policies), and we used multivariable multilevel modified Poisson regression analysis to assess the relation between unit PPS and outcomes.ResultsPolicies regarding visiting hours, duration of visits and possibility for parents to stay during medical rounds and spend the night in unit differed within and across countries. After adjustment for potential confounders, infants cared for in units with liberal parental policies (PPS≥7) were about twofold significantly more likely to be discharged with exclusive maternal milk feeding and exclusive direct breastfeeding.ConclusionUnit policies promoting parental presence and involvement in care may increase the likelihood of successful breastfeeding at discharge for very preterm infants.
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- Boj, Sylvia F, et al.
(författare)
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Organoid models of human and mouse ductal pancreatic cancer
- 2015
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Ingår i: Cell. - : Cell press. - 0092-8674 .- 1097-4172. ; 160:1-2, s. 324-338
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation, and exhibit ductal- and disease-stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy.
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- Corvigno, Sara, et al.
(författare)
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Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival
- 2016
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 7:14, s. 18573-18584
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Tidskriftsartikel (refereegranskat)abstract
- Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers alpha-SMA, PDGF beta R and desmin. Images were digitally analyzed to yield "metrics" related to vasculature and stroma features. Intra-case analyses showed that PDGF beta R in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning `-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGF beta R-positive stroma fraction and high PDGF beta FR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8). In conclusion, we found PDGF beta R- and alpha-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGF beta R in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer.
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- Corvigno, Sara, et al.
(författare)
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Multi-parametric profiling of renal cell, colorectal, and ovarian cancer identifies tumour-type-specific stroma phenotypes and a novel vascular biomarker
- 2017
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Ingår i: The journal of pathology. Clinical research. - : WILEY. - 2056-4538. ; 3:3, s. 214-224
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Tidskriftsartikel (refereegranskat)abstract
- A novel set of integrated procedures for quantification of fibroblast-rich stroma and vascular characteristics has recently been presented allowing discovery of novel perivascular and stromal biomarkers in colorectal, renal cell, and ovarian cancer. In the present study, data obtained through these procedures from clinically well-annotated collections of these three tumour types have been used to address two novel questions. First, data have been used to investigate if the three tumour types demonstrate significant differences regarding features such as vessel diameter, vessel density, and perivascular marker expression. Second, analyses of the cohorts have been used to explore the prognostic significance of a novel vascular metric, 'vessel distance inter-quartile range (IQR)' that describes intra-case heterogeneity regarding vessel distribution. The comparisons between the three tumour types demonstrated a set of significant differences. Vessel density of renal cell cancer was statistically significantly higher than in colorectal and ovarian cancer. Vessel diameter was statistically significantly higher in ovarian cancer. Concerning perivascular status, colorectal cancer displayed significantly higher levels of perivascular PDGFR-beta expression than the other two tumour types. Intra-case heterogeneity of perivascular PDGFR-beta expression was also higher in colorectal cancer. Notably, these fibroblast-dominated stroma phenotypes matched previously described experimental tumour stroma characteristics, which have been linked to differential sensitivity to anti-VEGF drugs. High 'vessel distance IQR' was significantly associated with poor survival in both renal cell cancer and colorectal cancer. In renal cell cancer, this characteristic also acted as an independent prognostic marker according to multivariate analyses including standard clinico-pathological characteristics. Explorative subset analyses indicated particularly strong prognostic significance of 'vessel distance IQR' in T stage 4 of this cancer type. Together, these analyses identified tumour-type-specific vascular-stroma phenotypes of possible functional significance, and suggest 'vessel distance IQR' as a novel prognostic biomarker.
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- van Gool, Jan D, et al.
(författare)
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Multi-center randomized controlled trial of cognitive treatment, placebo, oxybutynin, bladder training, and pelvic floor training in children with functional urinary incontinence.
- 2014
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Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467. ; 33:5, s. 482-487
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Functional urinary incontinence causes considerable morbidity in 8.4% of school-age children, mainly girls. To compare oxybutynin, placebo, and bladder training in overactive bladder (OAB), and cognitive treatment and pelvic floor training in dysfunctional voiding (DV), a multi-center controlled trial was designed, the European Bladder Dysfunction Study. METHODS: Seventy girls and 27 boys with clinically diagnosed OAB and urge incontinence were randomly allocated to placebo, oxybutynin, or bladder training (branch I), and 89 girls and 16 boys with clinically diagnosed DV to either cognitive treatment or pelvic floor training (branch II). All children received standardized cognitive treatment, to which these interventions were added. The main outcome variable was daytime incontinence with/without urinary tract infections. Urodynamic studies were performed before and after treatment. RESULTS: In branch I, the 15% full response evolved to cure rates of 39% for placebo, 43% for oxybutynin, and 44% for bladder training. In branch II, the 25% full response evolved to cure rates of 52% for controls and 49% for pelvic floor training. Before treatment, detrusor overactivity (OAB) or pelvic floor overactivity (DV) did not correlate with the clinical diagnosis. After treatment these urodynamic patterns occurred de novo in at least 20%. CONCLUSION: The mismatch between urodynamic patterns and clinical symptoms explains why cognitive treatment was the key to success, not the added interventions. Unpredictable changes in urodynamic patterns over time, the response to cognitive treatment, and the gender-specific prevalence suggest social stress might be a cause for the symptoms, mediated by corticotropin-releasing factor signaling pathways. Neurourol. Urodynam. © 2013 Wiley Periodicals, Inc.
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- Wenzel, H. H. B., et al.
(författare)
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A federated approach to identify women with early-stage cervical cancer at low risk of lymph node metastases
- 2023
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 185, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection.Methods: Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion cri-teria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+. Results: We included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio [OR] 5.16, 95% confidence interval [CI], 4.59-5.79), tumour size 21-40 mm (OR 2.14, 95% CI, 1.89-2.43) and depth of invasion > 10 mm (OR 1.81, 95% CI, 1.59-2.08). A group of 1469 women (41%)-with tumours without LVSI, tumour size 520 mm, and depth of invasion 510 mm-had a very low risk of pN + (2.4%, 95% CI, 1.7-3.3%). Conclusion: Early-stage cervical cancer without LVSI, a tumour size 520 mm and depth of invasion 510 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection.& COPY; 2023 Elsevier Ltd. All rights reserved.
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| 15. |
- Werdelin, Lars, et al.
(författare)
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Locating specimens of extinct tiger (Panthera tigris) subspecies: Caspian tiger (P. t. virgata), Javan tiger (P. t. sondaica), and Balinese tiger (P. t. balica) – including previously unpublished specimens
- 2013
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Ingår i: Mammal Study. - : Mammalogical Society of Japan. - 1343-4152 .- 1348-6160. ; 38, s. 187-198
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances in multivariate statistics, and in ancient DNA techniques, have greatly increased understanding of tiger phylogeography. However, regardless of advances in analytical methodology, researchers will continue to need access to specimens for morphological measurements and sampling for genetic analysis. The tiger has become increasingly endangered, and out of the nine putative tiger subspecies, three (Javan, Balinese, and Caspian) have become extinct in the last 100 years, leaving the specimens kept in natural history collections as the only materials available for research. Frustratingly little information is widely available concerning the specimens of these extinct tiger subspecies. We conducted an extensive search for specimens of extinct tiger subspecies, and also developed a simple on-site method to assign unprovenanced and probable Indonesian specimens to either Javan/Balinese or Sumatran subspecies. We located a total of 88 Javan, 11 Balinese, and 46 Caspian tigers, including seven new Javan tigers, and three Balinese tigers that were not widely known previously. These specimens are critical for research in order to understand the intraspecific phylogeny and evolutionary history of the tiger.
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