| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Berglund, Erik, et al.
(författare)
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Treatment effect expressed as the novel Delay of Event measure is associated with high willingness to initiate preventive treatment - A randomized survey experiment comparing effect measures
- 2016
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Ingår i: Patient Education and Counseling. - : Elsevier BV. - 0738-3991 .- 1873-5134. ; 99:12, s. 2005-2011
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study aimed to investigate patients' willingness to initiate a preventive treatment and compared two established effect measures to the newly developed Delay of Events (DoE) measure that expresses treatment effect as a gain in event-free time. Methods: In this cross-sectional, randomized survey experiment in the general Swedish population, 1079 respondents (response rate 60.9%) were asked to consider a preventive cardiovascular treatment. Respondents were randomly allocated to one of three effect descriptions: DoE, relative risk reduction (RRR), or absolute risk reduction (ARR). Univariate and multivariate analyses were performed investigating willingness to initiate treatment, views on treatment benefit, motivation and importance to adhere and willingness to pay for treatment. Results: Eighty-one percent were willing to take the medication when the effect was described as DoE, 83.0% when it was described as RRR and 62.8% when it was described as ARR. DoE and RRR was further associated with positive views on treatment benefit, motivation, importance to adhere and WTP. Conclusions: Presenting treatment effect as DoE or RRR was associated with a high willingness to initiate treatment. Practice implications: An approach based on the novel time-based measure DoE may be of value in clinical communication and shared decision making.
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| 3. |
- Braun, Emelie, et al.
(författare)
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Comprehensive cell atlas of the first-trimester developing human brain
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 382:6667, s. 172-
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Tidskriftsartikel (refereegranskat)abstract
- The adult human brain comprises more than a thousand distinct neuronal and glial cell types, a diversity that emerges during early brain development. To reveal the precise sequence of events during early brain development, we used single-cell RNA sequencing and spatial transcriptomics and uncovered cell states and trajectories in human brains at 5 to 14 postconceptional weeks (pcw). We identified 12 major classes that are organized as ~600 distinct cell states, which map to precise spatial anatomical domains at 5 pcw. We described detailed differentiation trajectories of the human forebrain and midbrain and found a large number of region-specific glioblasts that mature into distinct pre-astrocytes and pre–oligodendrocyte precursor cells. Our findings reveal the establishment of cell types during the first trimester of human brain development.
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| 4. |
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| 5. |
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| 6. |
- Huang, Biying, et al.
(författare)
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Effects of cigarette smoking on cardiovascular-related protein profiles in two community-based cohort studies
- 2016
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 254, s. 52-58
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Cardiovascular diseases account for the largest fraction of smoking-induced deaths. Studies of smoking in relation to cardiovascular-related protein markers can provide novel insights into the biological effects of smoking. We investigated the associations between cigarette smoking and 80 protein markers known to be related to cardiovascular diseases in two community-based cohorts, the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 969, 50% women, all aged 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 717, all men aged 77 years). Methods: Smoking status was self-reported and defined as current smoker, former smoker or never-smoker. Levels of the 80 proteins were measured using the proximity extension assay, a novel PCR-based proteomics technique. Results: We found 30 proteins to be significantly associated with current cigarette smoking in PIVUS (FDR<5%); and ten were replicated in ULSAM (p<0.05). Matrix metalloproteinase-12 (MMP-12), growth/differentiation factor 15 (GDF-15), urokinase plasminogen activator surface receptor (uPAR), TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), lectin-like oxidized LDL receptor 1 (LOX-1), hepatocyte growth factor (HGF), matrix metalloproteinase-10 (MMP-10) and matrix metalloproteinase-1 (MMP-1) were positively associated, while endothelial cell-specific molecule 1 (ESM-1) and interleukin-27 subunit alpha (IL27-A) showed inverse associations. All of them remained significant in a subset of individuals without manifest cardiovascular disease. Conclusions: The findings of the present study suggest that cigarette smoking may interfere with several essential parts of the atherosclerosis process, as evidenced by associations with protein markers representing endothelial dysfunction, inflammation, neointimal formation, foam cell formation and plaque instability. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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| 7. |
- Li, Xiaofei, et al.
(författare)
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Profiling spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin
- 2023
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Ingår i: Nature Neuroscience. - : Springer Nature. - 1097-6256 .- 1546-1726. ; 26:5, s. 891-901
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Tidskriftsartikel (refereegranskat)abstract
- The authors created a comprehensive developmental cell atlas for spatiotemporal gene expression of the human spinal cord, revealed species-specific regulation during development and used the atlas to infer novel markers for pediatric ependymomas. The spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. In this study, by performing integrated analysis of single-cell and spatial multi-omics data, we used 16 prenatal human samples to create a comprehensive developmental cell atlas of the spinal cord during post-conceptional weeks 5-12. This revealed how the cell fate commitment of neural progenitor cells and their spatial positioning are spatiotemporally regulated by specific gene sets. We identified unique events in human spinal cord development relative to rodents, including earlier quiescence of active neural stem cells, differential regulation of cell differentiation and distinct spatiotemporal genetic regulation of cell fate choices. In addition, by integrating our atlas with pediatric ependymomas data, we identified specific molecular signatures and lineage-specific genes of cancer stem cells during progression. Thus, we delineate spatiotemporal genetic regulation of human spinal cord development and leverage these data to gain disease insight.
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| 8. |
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| 9. |
- Nolte, I. M., et al.
(författare)
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Genetic loci associated with heart rate variability and their effects on cardiac disease risk
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
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| 10. |
- Nowak, Christoph, et al.
(författare)
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Metabolite profiles during an oral glucose tolerance test reveal new associations with clamp-measured insulin sensitivity
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Impaired insulin sensitivity (IS) is a major risk factor for cardiovascular disease and type 2 diabetes. Metabolomic profiling during an oral glucose tolerance test (OGTT) can reveal early pathogenic alterations in healthy individuals. Our aim was to identify IS biomarkers and gain new pathophysiologic insights by applying untargeted metabolomics to repeated OGTT plasma samples in association with a hyperinsulinemic-euglycemic clamp assessment. We studied 192 metabolites identified by non-targeted liquid chromatography/mass spectrometry in plasma samples taken at 0, 30, and 120 min during an OGTT in 470 non-diabetic 71-yr-old men. Insulin sensitivity was associated with 35 metabolites at one or more time points in multivariable-adjusted linear regression. The trajectories of nine metabolites during the OGTT were related to IS, six of which (oleic and palmitoleic acid, decanoyl- and dodecanoylcarnitine, deoxycholate-glycine and hexose) showed no associations with IS in the baseline fasting state. The strongest effects were detected for medium-chain acylcarnitines, which increased between 30-120 min in insulin-resistant individuals compared to those with normal IS. In this large community sample, we identified novel associations between clamp-measured IS and metabolite profiles that became apparent only after an oral glucose challenge. Associations of differential medium-chain acylcarnitine and monounsaturated fatty acid trajectories with IS provide new insights into the pathogenesis of insulin resistance.
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| 11. |
- Nowak, Christoph, et al.
(författare)
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Type 2 diabetes, glycaemic traits and cardiovascular disease : a Mendelian Randomization study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 diabetes (T2D) and its hallmarks insulin resistance, impaired insulin secretion, and hyperglycaemia affect over 400 million persons worldwide and are associated with raised cardiovascular risk, but their causal role has been difficult to dissect due to overlap between risk factors. We used Mendelian randomization analysis, which utilises genetic polymorphisms associated with a risk factor, to assess causal effects of T2D, insulin resistance, insulin secretion, and fasting glucose on mortality, ischaemic stroke, and coronary artery disease (CAD) risk in 120,091 adults in the UK Biobank and in the CARDIoGRAMplusC4D consortium (63,746 cases of CAD and 130,681 controls). We found evidence for a causal effect of T2D on raised CAD risk (odds ratio (OR) per doubling in the odds of T2D, 1.07, 95% confidence interval (CI) 1.05 – 1.09, P = 1.2 x 10-9) and for a causal effect of impaired insulin secretion on the risk of CAD (OR per SD-unit decrease, 1.14, 95% CI 1.06 – 1.22, P = 0.002). The genetic score for insulin resistance was associated with increased coronary artery disease risk; however, sensitivity analysis indicated that the instrument might not be appropriate to use for robust causal inference testing. Our results support previous reports of a causal role of T2D and impaired insulin secretion in coronary artery disease and point to a complex relationship between variants affecting insulin resistance and cardiovascular outcomes.
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| 12. |
- Olsen, Thale K., et al.
(författare)
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Joint single-cell genetic and transcriptomic analysis reveal pre-malignant SCP-like subclones in human neuroblastoma
- 2024
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Ingår i: MOLECULAR CANCER. - 1476-4598. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Neuroblastoma (NB) is a heterogeneous embryonal malignancy and the deadliest tumor of infancy. It is a complex disease that can result in diverse clinical outcomes. In some children, tumors regress spontaneously. Others respond well to existing treatments. But for the high-risk group, which constitutes approximately 40% of all patients, the prognosis remains dire despite collaborative efforts in basic and clinical research. While its exact cellular origin is still under debate, NB is assumed to arise from the neural crest cell lineage including multipotent Schwann cell precursors (SCPs), which differentiate into sympatho-adrenal cell states eventually producing chromaffin cells and sympathoblasts. Methods To investigate clonal development of neuroblastoma cell states, we performed haplotype-specific analysis of human tumor samples using single-cell multi-omics, including joint DNA/RNA sequencing of sorted single cells (DNTR-seq). Samples were also assessed using immunofluorescence stainings and fluorescence in-situ hybridization (FISH). Results Beyond adrenergic tumor cells, we identify subpopulations of aneuploid SCP-like cells, characterized by clonal expansion, whole-chromosome 17 gains, as well as expression programs of proliferation, apoptosis, and a non-immunomodulatory phenotype. Conclusion Aneuploid pre-malignant SCP-like cells represent a novel feature of NB. Genetic evidence and tumor phylogeny suggest that these clones and malignant adrenergic populations originate from aneuploidy-prone cells of migrating neural crest or SCP origin, before lineage commitment to sympatho-adrenal cell states. Our findings expand the phenotypic spectrum of NB cell states. Considering the multipotency of SCPs in development, we suggest that the transformation of fetal SCPs may represent one possible mechanism of tumor initiation in NB with chromosome 17 aberrations as a characteristic element.
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| 13. |
- Rowiński, Piotr K., et al.
(författare)
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Warming alters the body shape of European perch Perca fluviatilis
- 2015
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Ingår i: Journal of Fish Biology. - : Wiley. - 0022-1112 .- 1095-8649. ; 87:5, s. 1234-1247
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Tidskriftsartikel (refereegranskat)abstract
- The consequences of elevated temperature on body shape were investigated by comparing European perch Perca fluviatilis from the Forsmark area of the Baltic Sea to P. fluviatilis from a nearby Biotest enclosure. The Biotest is a man-made enclosure within the Baltic Sea that has received warm water from a nuclear power plant since 1980, resulting in temperatures that are elevated 5-10 degrees C relative to the surrounding Baltic Sea. Sampled fish ranged from young-of-the-year to 14years. Geometric morphometrics and multivariate statistical analysis revealed significant morphological differences between individuals of P. fluviatilis from these two habitats. Most importantly, relative shape changed with size, with small individuals of P. fluviatilis from Biotest being characterized by a deeper body shape and a larger caudal peduncle than the smaller Baltic individuals. In large specimens, smaller differences were found with Biotest individuals being more slender than Baltic individuals. These results show that, in order to have a full understanding of the biological effects of elevated temperatures, studies that cover the entire size range of organisms will be important. Apart from the direct influence of temperature on growth rate and body shape, other ecological factors affected by temperature are discussed as possible contributors to the observed differences between the two populations.
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| 14. |
- Sountoulidis, Alexandros, et al.
(författare)
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SCRINSHOT enables spatial mapping of cell states in tissue sections with single-cell resolution
- 2020
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 18:11
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Tidskriftsartikel (refereegranskat)abstract
- Changes in cell identities and positions underlie tissue development and disease progression. Although single-cell mRNA sequencing (scRNA-Seq) methods rapidly generate extensive lists of cell states, spatially resolved single-cell mapping presents a challenging task. We developed SCRINSHOT (Single-Cell Resolution IN Situ Hybridization On Tissues), a sensitive, multiplex RNA mapping approach. Direct hybridization of padlock probes on mRNA is followed by circularization with SplintR ligase and rolling circle amplification (RCA) of the hybridized padlock probes. Sequential detection of RCA-products using fluorophore-labeled oligonucleotides profiles thousands of cells in tissue sections. We evaluated SCRINSHOT specificity and sensitivity on murine and human organs. SCRINSHOT quantification of marker gene expression shows high correlation with published scRNA-Seq data over a broad range of gene expression levels. We demonstrate the utility of SCRINSHOT by mapping the locations of abundant and rare cell types along the murine airways. The amenability, multiplexity, and quantitative qualities of SCRINSHOT facilitate single-cell mRNA profiling of cell-state alterations in tissues under a variety of native and experimental conditions.
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| 15. |
- Sundstrom, Erik, et al.
(författare)
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Service innovation as a political process
- 2017
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Ingår i: Service Industries Journal. - Oxon, UK : Taylor & Francis. - 0264-2069 .- 1743-9507. ; 37:5-6, s. 341-362
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Tidskriftsartikel (refereegranskat)abstract
- Service innovation processes are driven by stakeholders in interaction and are understood and sketched as a value negotiation process that consists of an iterative process of securing potential value in service. While previous research has focused on service innovation as a harmonious closed system, our study explores service innovation as a political process in which stakeholders negotiate to create and secure future value. Data are collected through interviews and participant observations in four different case studies. Our study contributes to the field by illuminating service innovation as a political process and explaining how this is operationalized. The findings also contribute to an understanding of how stakeholder resources impact a chosen strategy; the resulting strategy's impact on the service concept vis-a-vis its potential value; and how several involved stakeholders formulate, negotiate, and secure future potential value, which are the activities that drive a service innovation process.
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| 16. |
- Tallberg, Ing-Mari, et al.
(författare)
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Investigating medical decision-making capacity in patients with cognitive impairment using a protocol based on linguistic features
- 2013
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 54:5, s. 386-392
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Tidskriftsartikel (refereegranskat)abstract
- A critical question is whether cognitively impaired patients have the competence for autonomous decisions regarding participation in clinical trials. The present study aimed to investigate medical decision-making capacity by use of a Swedish linguistic instrument for medical decision-making (LIMD) in hypothetical clinical trials in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Three comparable groups (age, education) participated in the study: AD (n=20; MMSE: 24.1 +/- 3.3) and MCI (n=22; MMSE: 26.7 +/- 2.4) patients and healthy controls (n=37; MMSE: 29.1 +/- 1.0). Medical decision-making capacity was operationalized as answers to questions regarding participation in three hypothetical clinical trials. Answers were scored regarding comprehension, evaluation and intelligibility of decisions, and a total LIMD score was used as the measure of medical decision-making ability. Groups differed significantly in LIMD with AD patients performing worst and MCI poorer than the control group. A strong association was found between all LIMD scores and diagnosis which supported the assertion that LIMD as it is designed is a one-dimensional instrument of medical decision-making capacity (MDMC). The results indicate that a fundamental communicative ability has an impact on the competence for autonomous decisions in cognitive impairment.
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| 17. |
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| 18. |
- Widell, Anders, et al.
(författare)
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Antibody to hepatitis-C-virus-related proteins in sera from alanine-aminotransferase-screened blood donors and prospectively studied recipients
- 1991
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Ingår i: Vox Sanguinis. - 1423-0410. ; 60:1, s. 28-33
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Tidskriftsartikel (refereegranskat)abstract
- A prospective study of posttransfusion non-A, non-B hepatitis was conducted in Malmo, Sweden, in 1984-1985, in which donors were alanine aminotransferase (ALT) screened but not ALT selected. Among 741 patients studied at 0, 6, and 12 weeks after transfusion, 13 developed non-A, non-B hepatitis, and these were further followed up. Stored sera from the 13 hepatitis patients and their 123 donors were tested for anti-hepatitis C virus (HCV) by ELISA and if positive, analyzed by recombinant immunoblot assay (RIBA). All ALT-elevated blood units (n = 301) and a similar number of ALT-normal units were also tested. Only 4/13 patients with non-A, non-B hepatitis seroconverted to anti-HCV, all with ALT peaks greater than 10 times the upper normal. All seroconversions occurred within 5 months after transfusion and could be confirmed by RIBA. Hepatitis C in recipients occurred both after transfusion of blood that was strongly positive, weakly positive, and/or negative for anti-HCV by ELISA. In donors grouped by ALT levels, the anti-HCV prevalence varied between 0.4 (normal ALT) and 14% (ALT elevated greater than or equal to 2 times). Of the total of 9 donor units positive by ELISA, only 5 were confirmed by RIBA. Of the 5 recipients of the RIBA-positive blood units, 3 went into hepatitis, 1 remained normal at 10.5 weeks, and 1 showed a slight, transient ALT elevation at week 12. The recipients of ELISA-positive but RIBA-negative blood remained healthy.
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| 19. |
- Widell, Anders, et al.
(författare)
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Hepatitis C virus RNA in blood donor sera detected by the polymerase chain reaction: comparison with supplementary hepatitis C antibody assays
- 1991
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Ingår i: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 35:4, s. 253-258
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Tidskriftsartikel (refereegranskat)abstract
- The low specificity of screening ELISAs for antibodies to hepatitis C virus in blood donors has called for confirmatory tests. Two types of supplementary antibody assays are available, recombinant immunoblot assays (RIBA-1 and RIBA-2) and an antibody consumption test referred to as a neutralization assay. Amplification of viral nucleic acid by the polymerase chain reaction (PCR) provides an antibody independent mode of detecting viral infection. We applied reverse transcription-double PCR to detect an HCV 5'-noncoding viral RNA sequence in serum specimens and compared PCR findings with confirmatory antibody tests. This study includes sera from 37 blood donors found positive by the Ortho anti-HCV (C100-3) ELISA out of 14,591 donations. Of the 37 positive sera, 8 were positive by RIBA-1 and 1 further by RIBA-2. Seven of the RIBA positive sera contained HCV RNA by PCR. Among the 8 indeterminate and the 21 negative donor sera by RIBA-I, no PCR positive serum was found. The 37 anti-HCV positive donor sera identified by Ortho ELISA were also tested by Abbott anti-HCV (C100-3) ELISA whereby 22 were positive. Of these 22 sera plus 1 further with ELISA OD just below cutoff, 8 were positive by the neutralization assay, (Abbott Laboratories, North Chicago, IL, USA) and 6 of these, including the borderline serum, were PCR positive. One of the two neutralizable but PCR negative sera was RIBA positive and the other was indeterminate. However, one ELIS. A (Abbott Laboratories) positive (OD 1.99) serum was not neutralizable but nevertheless contained HCV RNA by PCR. Thus in blood donor sera, anti-HCV (C100-3) reactivity confirmed by RIBA or neutralization correlated well with the presence of HCV RNA.
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| 20. |
- Widell, Anders, et al.
(författare)
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Post-transfusion hepatitis type non-A, non-B in southern Sweden: occurrence and clinical significance
- 1987
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 19:6, s. 603-610
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Tidskriftsartikel (refereegranskat)abstract
- Two prospective studies of the occurrence and clinical significance of post-transfusion hepatitis non-A, non-B were performed in Malmo, Sweden. In both studies, patients of a broad clinical spectrum were followed up 6 and 12 weeks after transfusion. In a 7 week study from 1983, hepatitis non-A, non-B occurred in 9/173 transfused patients (5.2%) versus 1/203 untransfused controls (0.5%) (p less than 0.01). In a 6 month study from 1984-85, the incidence of hepatitis non-A, non-B had declined to 2.4% (18/739 transfused patients). The mean number of transfused units was about 5 in both studies and most patients had subclinical disease. Despite similar transfusion volumes to patients above or below 70 years of age, hepatitis non-A, non-B was predominantly seen among patients less than 70 years. In the 1984-85 study, hepatitis non-A, non-B incidence was 1.2% in recipients greater than or equal to 70 years, 3.4% in recipients less than 70 years and 4.5% in recipients less than 40 years. One year after the initial hepatitis non-A, non-B episode, 4/18 patients (22%) had biochemical signs of chronic hepatitis.
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| 21. |
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| 22. |
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