scholarly journals Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
O. C. Bedoya-Reina ◽  
W. Li ◽  
M. Arceo ◽  
M. Plescher ◽  
P. Bullova ◽  
...  
Keyword(s):  
High Risk ◽  
Adrenal Gland ◽  
Chromaffin Cells ◽  
Risk Groups ◽  
Age At Diagnosis ◽  
Malignant Cells ◽  
Human Neuroblastoma ◽  
Embryonic Mouse ◽  
Clinical Risk Groups ◽  
Disease Entities

AbstractChildhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. Here we study single-cell and single-nuclei transcriptomes of neuroblastoma with different clinical risk groups and stages, including healthy adrenal gland. We compare tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles a subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations reveal different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome.

scholarly journals Single-nuclei transcriptomes from human adrenal gland reveals distinct cellular identities of low and high-risk neuroblastoma tumors.

2021 ◽  
Author(s):  
Oscar C Bedoya-Reina ◽  
Wenyu Li ◽  
Maria Arceo ◽  
Monika Plescher ◽  
Petra Bullova ◽  
...  
Keyword(s):  
High Risk ◽  
Adrenal Gland ◽  
Chromaffin Cells ◽  
Risk Groups ◽  
Age At Diagnosis ◽  
Malignant Cells ◽  
Human Neuroblastoma ◽  
Embryonic Mouse ◽  
Clinical Risk Groups ◽  
Disease Entities

Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. We studied single-cell and single-nuclei transcriptomes of neuroblastoma with different clinical risk groups and stages, including healthy adrenal gland. We compared tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles an unknown subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations revealed different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome.

scholarly journals Immunosurveillance of childhood ALL: polymorphic interferon-γ alleles are associated with age at diagnosis and clinical risk groups

Leukemia ◽  
2004 ◽  
Vol 19 (1) ◽  
pp. 44-48 ◽  
Author(s):  
T Cloppenborg ◽  
M Stanulla ◽  
M Zimmermann ◽  
M Schrappe ◽  
K Welte ◽  
...  
Keyword(s):  
Risk Groups ◽  
Interferon Γ ◽  
Age At Diagnosis ◽  
Childhood All ◽  
Clinical Risk ◽  
Clinical Risk Groups

scholarly journals BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups

2014 ◽  
Vol 211 (4) ◽  
pp. 669-683 ◽  
Author(s):  
Marie-Luise Berres ◽  
Karen Phaik Har Lim ◽  
Tricia Peters ◽  
Jeremy Price ◽  
Hitoshi Takizawa ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
High Risk ◽  
Somatic Mutation ◽  
Risk Groups ◽  
Low Risk ◽  
Braf V600e ◽  
Increased Risk ◽  
Clinical Risk Groups ◽  
Myeloid Neoplasia

Langerhans cell histiocytosis (LCH) is a clonal disorder with elusive etiology, characterized by the accumulation of CD207+ dendritic cells (DCs) in inflammatory lesions. Recurrent BRAF-V600E mutations have been reported in LCH. In this study, lesions from 100 patients were genotyped, and 64% carried the BRAF-V600E mutation within infiltrating CD207+ DCs. BRAF-V600E expression in tissue DCs did not define specific clinical risk groups but was associated with increased risk of recurrence. Strikingly, we found that patients with active, high-risk LCH also carried BRAF-V600E in circulating CD11c+ and CD14+ fractions and in bone marrow (BM) CD34+ hematopoietic cell progenitors, whereas the mutation was restricted to lesional CD207+ DC in low-risk LCH patients. Importantly, BRAF-V600E expression in DCs was sufficient to drive LCH-like disease in mice. Consistent with our findings in humans, expression of BRAF-V600E in BM DC progenitors recapitulated many features of the human high-risk LCH, whereas BRAF-V600E expression in differentiated DCs more closely resembled low-risk LCH. We therefore propose classification of LCH as a myeloid neoplasia and hypothesize that high-risk LCH arises from somatic mutation of a hematopoietic progenitor, whereas low-risk disease arises from somatic mutation of tissue-restricted precursor DCs.

Immunosurveillance of childhood ALL - Polymorphic Interferon-γ alleles are associated with age at diagnosis and clinical risk groups

2004 ◽  
Vol 216 (03) ◽  
Author(s):  
T Cloppenborg ◽  
M Stanulla ◽  
M Zimmermann ◽  
M Schrappe ◽  
K Welte ◽  
...  
Keyword(s):  
Risk Groups ◽  
Interferon Γ ◽  
Age At Diagnosis ◽  
Childhood All ◽  
Clinical Risk ◽  
Clinical Risk Groups

scholarly journals Age dependence of modern clinical risk groups for localized prostate cancer – a population-based study

2019 ◽  
Author(s):  
Minh-Phuong Huynh-Le ◽  
Tor Åge Myklebust ◽  
Christine H. Feng ◽  
Roshan Karunamuni ◽  
Tom Børge Johannesen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Gleason Score ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Clinical Risk ◽  
High Risk Disease ◽  
Clinical Risk Groups

AbstractBackgroundOptimal prostate cancer (PCa) screening strategies will focus on men most likely to have potentially-lethal, localized disease. Age-specific incidence rates (ASIRs) for clinical risk groups could guide risk-stratified screening.ObjectiveDetermine ASIRs and proportions of PCa diagnoses in Norway for modern risk-group and Gleason score categories.Design, Setting, and ParticipantsAll men diagnosed with PCa in Norway in 2014-2017 (n=20,356).Outcome Measurements and Statistical AnalysisPatients were assigned to clinical risk groups: low, favorable-intermediate, unfavorable-intermediate, high, regional, and metastatic, using Gleason score and clinical stage. Associations were assessed between age and (1) Gleason score (including Gleason 3+4 and 4+3) and (2) PCa risk group. Risk-group ASIRs were calculated by multiplying the overall Norwegian ASIR by the proportions observed for each category.ResultsOlder age was significantly associated with higher Gleason score and more advanced disease. For example, among men aged 55-59, 65-69, 75-79, and 85-89 years, the percentage with Gleason 8-10 disease was 16.5%, 23.4%, 37.2%, and 59.9%, respectively (p<0.001); the percentage with at least high-risk disease was 29.3%, 39.1%, 60.4%, and 90.6%, respectively. Corresponding percentages for low-risk PCa were 24.0%, 17.9%, 10.2%, and 4.1% (p<0.001). The respective maximum ASIRs (per 100,000 men) for low-risk, favorable-intermediate-risk, unfavorable-intermediate-risk, high-risk, regional, and metastatic disease were: 157.1, 183.8, 194.8, 408.3, 172.3, and 330.0; incidence for low-risk and favorable-intermediate-risk PCa peaked before age 70, while more advanced categories peaked after 70. At age 75-79 years, the ASIR of high-risk disease was approximately 6 times greater than at 55-59 years.ConclusionsRisk of clinically-significant, localized PCa increases with age. Healthy older men may be among those most likely to benefit from PCa screening.

Plasma Biomarker Profiling In Langerhans Cell Histiocytosis: Risk-Stratifying The Inflammatory Storm

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2854-2854
Author(s):  
Miguel Dario Cantu ◽  
Tricia L Peters ◽  
Karen Phaik-Har Lim ◽  
Albert Shih ◽  
Rikhia Chakraborty ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Langerhans Cell Histiocytosis ◽  
Risk Groups ◽  
Langerhans Cell ◽  
Response To Therapy ◽  
Low Risk ◽  
Clinical Risk ◽  
Clinical Risk Groups ◽  
Single Lesion

Abstract Introduction Despite indistinguishable histology and the common feature of Birbeck granules in lesion biopsies, clinical presentation of patients with Langerhans Cell Histiocytosis (LCH) is highly variable, from single lesion cured by curretage, to multi-system disease requiring aggressive chemotherapy or stem cell transplant. Risk stratification for Langerhans Cell Histiocytosis has historically assigned clinical risk groups based on anatomic location and extent of LCH lesions, which is the basis for dose and duration of chemotherpy on recent Histiocyte Society trials. In this study, we test the hypothesis that distinct subgroups of patients with LCH may be identified by relative levels of circulating biomarkers. Methods Pre-therapy plasma was collected on 97 patients with LCH (82 Pediatric: 17 High-Risk, 23 Multisystem/Multifocal “Non-risk”, 42 Single Lesion “Non-risk”; 15 Adult: 5 High-Risk, 5 Multisystem/Multifocal “Non-risk”, 5 Single Lesion “Non-risk”) and 49 control subjects (32 Pediatric, 17 Adult). Quantitative levels of plasma proteins (158 analytes) was determined by multiplex analysis with Millipore MagPix kits and the Luminex plate reader. Data were analyzed with both unsupervised and supervised methodologies. Results Consensus clustering with non-negative matrix factorization (NMF) clusters identified three groups which were analyzed along with clinical categories. Significant clinical variables included age (adult samples clustered in NMF group 1) and LCH risk category (High-Risk LCH samples clustered in NMF group 3). Samples from patients with the BRAF-V600Emutation or relapse within 1 year did not cluster into any NMF group with signifiance. Additionally, supervised analysis identified specific molecules that were significantly differentially expressed between different clinical categories after multiple testing correction (FDR<0.10): Pediatric LCH vs Adult LCH (72 molecules significant, largest differences in MMP-3, MMP-2 and osteopontin); Pediatric Control vs Pediatric LCH (66 molecules significant, largest differences in SDF-1a, IL-20, MIP-1d, FGF-2 and sIL-4R); Pediatric Low-Risk vs Pediatric High-Risk (47 molecules significant, largest differences in sTNF-R11, sTNF-RI, I-309, sIL2Ra and osteopontin). While previous studies have analyzed expression differences of cytokines in LCH lesions and plasma, in this study the most striking differences are between control vs LCH samples are chemokine molecules. The largest differences between Low-Risk and High-Risk LCH patients include inflammatory cytokines and receptors. Conclusions Despite mounting evidence supporting pathogenesis of LCH as a myeloid neoplasia arising from immature dendritic cell precursors, these results are consistent with exuberant chemokine and cytokine expression in patients with active LCH, supporting a potential role for inflammation in pathogenesis. This study demonstrates the feasibility of identifying novel LCH sub-groups according to plasma protein profiles with unsupervised analysis, and significant differences can be detected in protein levels between clinical risk groups. Future studies will validate the clinical utility of plasma biomarkers in diagnosis, risk-stratification and determining response to therapy. Finally, feasibility of collecting plasma compared to viable lesions makes plasma studies ideal for prospective collection and analysis in cooperative group studies. Disclosures: No relevant conflicts of interest to declare.

Suicide in Nógrád County, Hungary, 1970-1994

Crisis ◽  
1999 ◽  
Vol 20 (2) ◽  
pp. 64-70 ◽  
Author(s):  
Tamás Zonda
Keyword(s):  
High Risk ◽  
Psychiatric Disorders ◽  
Suicide Rate ◽  
Risk Groups ◽  
The Elderly ◽  
Female Ratio ◽  
Suicide Notes ◽  
Suicidal Intention ◽  
Male Female Ratio

The author examined completed suicides occurring over a period of 25 years in a county of Hungary with a traditionally low (relatively speaking) suicide rate of 25.8. The rates are clearly higher in villages than in the towns. The male/female ratio was close to 4:1, among elderly though only 1.5:1. The high risk groups are the elderly, divorced, and widowed. Violent methods are chosen in 66.4% of the cases. The rates are particularly high in the period April-July. Prior communication of suicidal intention was revealed in 16.3% of all cases. Previous attempts had been undertaken by 17%, which in turn means that 83% of suicides were first attempts. In our material 10% the victims left suicide notes. Psychiatric disorders were present in 60.1% of the cases, and severe, multiple somatic illnesses (including malignomas) were present in 8.8%. The majority of the data resemble those found in the literature.

A(H1N1)v cases of the 2009/2010 and 2010/2011 influenza seasons in the Medical and Health Sciences Centre of Debrecen University

2012 ◽  
Vol 153 (17) ◽  
pp. 649-654
Author(s):  
Piroska Orosi ◽  
Judit Szidor ◽  
Tünde Tóthné Tóth ◽  
József Kónya
Keyword(s):  
High Risk ◽  
Influenza Season ◽  
National Level ◽  
Organ Transplant ◽  
High Risk Patient ◽  
Risk Groups ◽  
Health Sciences ◽  
World Health ◽  
Transplant Patients ◽  
Health Organization

The swine-origin new influenza variant A(H1N1) emerged in 2009 and changed the epidemiology of the 2009/2010 influenza season globally and at national level. Aims: The aim of the authors was to analyse the cases of two influenza seasons. Methods: The Medical and Health Sciences Centre of Debrecen University has 1690 beds with 85 000 patients admitted per year. The diagnosis of influenza was conducted using real-time polymerase chain reaction in the microbiological laboratories of the University and the National Epidemiological Centre, according to the recommendation of the World Health Organization. Results: The incidence of influenza was not higher than that observed in the previous season, but two high-risk patient groups were identified: pregnant women and patients with immunodeficiency (oncohematological and organ transplant patients). The influenza vaccine, which is free for high-risk groups and health care workers in Hungary, appeared to be effective for prevention, because in the 2010/2011 influenza season none of the 58 patients who were administered the vaccination developed influenza. Conclusion: It is an important task to protect oncohematological and organ transplant patients. Orv. Hetil., 2012, 153, 649–654.

ON THE ROLE OF BIOMONITORING IN THE ASSESSMENT OF THE HEALTH OF THE POPULATION EXPOSED TO MERCURY

2017 ◽  
pp. 2-7
Author(s):  
L. V. Lukovnikova ◽  
G. I. Sidorin ◽  
L. A. Alikbaeva ◽  
A. V. Galochina
Keyword(s):  
High Risk ◽  
Biological Monitoring ◽  
Clinical Examination ◽  
Inorganic Compounds ◽  
Risk Groups ◽  
Comprehensive Approach ◽  
Chemical Monitoring ◽  
Environmental Objects

When examining the population exposed to organic and inorganic compounds of mercury, a comprehensive approach is proposed, including chemical monitoring of environmental objects, biological monitoring, clinical examination of persons exposed to mercury, identification of high-risk groups.

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