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  • 1
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    Neurological manifestations of COVID-19 in adults and children
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 4 ( 2023-04-19), p. 1648-1661
    Details
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 4 ( 2023-04-19), p. 1648-1661
    Abstract: Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P & lt; 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac332
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
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  • 2
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    Differences in Outcomes Reported by Patients With Inflammatory Bowel Diseases vs Their Health Care Professionals
    Elsevier BV ; 2019
    In:  Clinical Gastroenterology and Hepatology Vol. 17, No. 10 ( 2019-09), p. 2050-2059.e1
    Details
    In: Clinical Gastroenterology and Hepatology, Elsevier BV, Vol. 17, No. 10 ( 2019-09), p. 2050-2059.e1
    Type of Medium: Online Resource
    ISSN: 1542-3565
    URL: Article
    DOI: 10.1016/j.cgh.2018.11.029
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
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  • 3
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    Intrabronchial Infection of Rhesus Macaques with Simian Varicella Virus Results in a Robust Immune Response in the Lungs
    American Society for Microbiology ; 2014
    In:  Journal of Virology Vol. 88, No. 21 ( 2014-11), p. 12777-12792
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 88, No. 21 ( 2014-11), p. 12777-12792
    Abstract: Varicella-zoster virus (VZV) is the etiological agent of varicella (chickenpox) and herpes zoster (shingles). Primary VZV infection is believed to occur via the inhalation of virus either in respiratory droplets or from shedding varicella lesions or by direct contact with infectious vesicular fluid. However, the ensuing immune response in the lungs remains incompletely understood. We have shown that intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, recapitulates the hallmarks of acute and latent VZV infection in humans. In this study, we performed an in-depth analysis of the host immune response to acute SVV infection in the lungs and peripheral blood. We report that acute SVV infection results in a robust innate immune response in the lungs, characterized by the production of inflammatory cytokines, chemokines, and growth factors as well as an increased frequency of plasmacytoid dendritic cells (DCs) that corresponded with alpha interferon (IFN-α) production and a rapid decrease in viral loads in the lungs. This is followed by T and B cell proliferation, antibody production, T cell differentiation, and cytokine production, which correlate with the complete cessation of viral replication. Although terminally differentiated CD8 T cells became the predominant T cell population in bronchoalveolar lavage cells, a higher percentage of CD4 T cells were SVV specific, which suggests a critical role for these cells in the resolution of primary SVV infection in the lungs. Given the homology between SVV and VZV, our data provide insight into the immune response to VZV within the lung. IMPORTANCE Although primary VZV infection occurs primarily via the respiratory route, the host response in the lungs and its contribution to the cessation of viral replication and establishment of latency remain poorly understood. The difficulty in accessing lung tissue and washes from individuals infected with VZV has hampered efforts to address this knowledge gap. SVV infection of rhesus macaques is an important model of VZV infection of humans; therefore, we utilized this animal model to gain a comprehensive view of the kinetics of the immune response to SVV in the lung and its relationship to the resolution of acute infection in respiratory tissues. These data not only advance our understanding of host immunity to VZV, a critical step in developing new vaccines, but also provide additional insight into immunity to respiratory pathogens.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.01814-14
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2014
    detail.hit.zdb_id: 1495529-5
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  • 4
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    Infection and immune control of human oncogenic γ-herpesviruses in humanized mice
    The Royal Society ; 2019
    In:  Philosophical Transactions of the Royal Society B: Biological Sciences Vol. 374, No. 1773 ( 2019-05-27), p. 20180296-
    Details
    In: Philosophical Transactions of the Royal Society B: Biological Sciences, The Royal Society, Vol. 374, No. 1773 ( 2019-05-27), p. 20180296-
    Abstract: Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) comprise the oncogenic human γ-herpesvirus family and are responsible for 2–3% of all tumours in man. With their prominent growth-transforming abilities and high prevalence in the human population, these pathogens have probably shaped the human immune system throughout evolution for near perfect immune control of the respective chronic infections in the vast majority of healthy pathogen carriers. The exclusive tropism of EBV and KSHV for humans has, however, made it difficult in the past to study their infection, tumourigenesis and immune control in vivo . Mice with reconstituted human immune system components (humanized mice) support replication of both viruses with both persisting latent and productive lytic infection. Moreover, B-cell lymphomas can be induced by EBV alone and KSHV co-infection with gene expression hallmarks of human malignancies that are associated with both viruses. Furthermore, cell-mediated immune control by primarily cytotoxic lymphocytes is induced upon infection and can be probed for its functional characteristics as well as putative requirements for its priming. Insights that have been gained from this model and remaining questions will be discussed in this review. This article is part of the theme issue ‘Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses’.
    Type of Medium: Online Resource
    ISSN: 0962-8436 , 1471-2970
    URL: Article
    DOI: 10.1098/rstb.2018.0296
    RVK:
    WA 15000
    Language: English
    Publisher: The Royal Society
    Publication Date: 2019
    detail.hit.zdb_id: 1462620-2
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  • 5
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    Diabetes Mellitus and Autoimmune Hepatitis: Demographical and Clinical Description of a Relatively Rare Phenotype
    Georg Thieme Verlag KG ; 2018
    In:  Hormone and Metabolic Research Vol. 50, No. 07 ( 2018-07), p. 568-574
    Details
    In: Hormone and Metabolic Research, Georg Thieme Verlag KG, Vol. 50, No. 07 ( 2018-07), p. 568-574
    Abstract: We studied demographic, metabolic, and clinical characteristics of patients with diabetes and autoimmune hepatitis (AIH) from the German/Austrian DPV registry. A total of 139 patients with diabetes and AIH were analyzed and compared to 437 728 patients with diabetes without AIH. The prevalence of AIH in patients with T1DM (44.8/100 000) seems higher than in the general population, the prevalence of AIH in patients with T2DM (23.6/100 000) does not seem to be increased. Patients with T2DM and AIH had a shorter duration of diabetes (p=0.007) and a higher proportion of females (p 〈 0.001) compared to T2DM without AIH. Patients with diabetes (T1DM or T2DM) and AIH required higher insulin doses (p 〈 0.001 and p=0.03, respectively) and showed increased liver enzymes (aspartate transaminase, alanine transaminase, gamma-glutamyltransferase) compared to diabetes patients without (all p 〈 0.001). We detected a lower percentage of patients treated with oral antidiabetic drugs (p=0.01) and a higher percentage of patients treated by insulin in patients with T2DM and AIH (p 〈 0.001) compared to patients with T2DM alone. We observed a higher incidence of autoimmune thyroid disease (AIT) in patients with diabetes (T1DM or T2DM) and AIH (p 〈 0.001) compared to diabetes patients without AIH. AIH seems more frequent in patients with T1DM. Patients with diabetes and AIH require intensification of antidiabetic therapy and seem to have a higher prevalence of AIT.
    Type of Medium: Online Resource
    ISSN: 0018-5043 , 1439-4286
    URL: Article
    DOI: 10.1055/a-0631-2468
    RVK:
    XA 46918
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2018
    detail.hit.zdb_id: 2056576-8
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  • 6
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    Genotype–phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients
    Springer Science and Business Media LLC ; 2021
    In:  BMC Gastroenterology Vol. 21, No. 1 ( 2021-08-03)
    Details
    In: BMC Gastroenterology, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-08-03)
    Abstract: Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 ( NLRP3 ) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). Methods We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. Results In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. Conclusions In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.
    Type of Medium: Online Resource
    ISSN: 1471-230X
    URL: Article
    DOI: 10.1186/s12876-021-01880-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041351-8
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  • 7
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    Lifestyle factors associated with inflammatory bowel disease: data from the Swiss IBD cohort study
    Springer Science and Business Media LLC ; 2023
    In:  BMC Gastroenterology Vol. 23, No. 1 ( 2023-03-12)
    Details
    In: BMC Gastroenterology, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-03-12)
    Abstract: Various environmental risk factors have been associated with the pathogenesis of inflammatory bowel disease. In this study we aimed to identify lifestyle factors that affect the onset of Crohn’s disease and ulcerative colitis. Methods 2294 patients from the Swiss IBD Cohort Study received a questionnaire regarding physical activity, nutritional habits and status of weight. In addition, a control group was formed comprising patients’ childhood friends, who grew up in a similar environment. Results Overall, 1111 questionnaires were returned (response rate: 48.4%). Significantly more patients with inflammatory bowel disease reported no regular practice of sport during childhood and beginning of adulthood compared to the control group ( p  = 0.0001). No association between intake of refined sugar and onset of inflammatory bowel disease was observed. More patients with Crohn’s disease compared to ulcerative colitis and controls suffered from overweight during childhood (12.8% vs. 7.7% and 9.7%, respectively; p  = 0.027). Conclusions Our study underlines the relevance of environmental factors in the development of inflammatory bowel disease. Our results imply a protective effect of physical activity regarding the onset of inflammatory bowel disease.
    Type of Medium: Online Resource
    ISSN: 1471-230X
    URL: Article
    DOI: 10.1186/s12876-023-02692-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041351-8
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  • 8
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    The personality traits activity, self-reproach, and negative affect jointly predict clinical recurrence, depressive symptoms, and low quality of life in inflammatory bowel disease patients
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Gastroenterology Vol. 57, No. 11 ( 2022-11), p. 848-866
    Details
    In: Journal of Gastroenterology, Springer Science and Business Media LLC, Vol. 57, No. 11 ( 2022-11), p. 848-866
    Abstract: The bidirectional “gut-brain axis” has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). While the influence of stress and depressive symptoms on IBD is well-characterized, the role of personality remains insufficiently investigated. Methods Personality was assessed in 1154 Swiss IBD cohort study (SIBDCS) patients via the NEO-Five-Factor Inventory (NEO-FFI) as well as in 2600 participants of the population-based CoLaus¦PsyCoLaus cohort study (NEO-FFI-revised). The NEO-FFI subcomponents activity, self-reproach and negative affect were associated with higher IBD disease activity and were combined to a NEO-FFI risk score. This risk score was validated and its effect on clinical IBD course and psychological endpoints was analysed in time-to-event and cumulative incidence analyses. Results In time-to-event analyses, a high NEO-FFI risk score was predictive for the clinical endpoints of new extraintestinal manifestation [EIM, adjusted hazard ratio (aHR) = 1.64, corrected p value ( q ) = 0.036] and two established composite flare endpoints (aHR = 1.53–1.63, q  = 0.003–0.006) as well as for the psychological endpoints depressive symptoms (aHR = 7.06, q   〈  0.001) and low quality of life (aHR = 3.06, q   〈  0.001). Furthermore, cumulative incidence analyses showed that patients at high NEO-FFI risk experienced significantly more episodes of active disease, new EIMs, one of the flare endpoints, depressive episodes and low disease-related quality of life. Personalities of IBD patients showed only minor differences from the general population sample (Pearson’s r  = 0.03–0.14). Conclusions Personality assessed by the NEO-FFI contained considerable predictive power for disease recurrence, depressive symptoms and low quality of life in IBD patients. Nevertheless, the personalities of IBD patients did not substantially differ from the general population.
    Type of Medium: Online Resource
    ISSN: 0944-1174 , 1435-5922
    URL: Article
    DOI: 10.1007/s00535-022-01902-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1473159-9
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  • 9
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    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study
    Springer Science and Business Media LLC ; 2021
    In:  Infection Vol. 49, No. 5 ( 2021-10), p. 889-905
    Details
    In: Infection, Springer Science and Business Media LLC, Vol. 49, No. 5 ( 2021-10), p. 889-905
    Abstract: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P   〈  0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.
    Type of Medium: Online Resource
    ISSN: 0300-8126 , 1439-0973
    URL: Article
    DOI: 10.1007/s15010-021-01599-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2006315-5
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  • 10
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    Evaluating the Cost-Effectiveness of Early Compared with Late or No Biologic Treatment to Manage Crohn’s Disease using Real-World Data
    Oxford University Press (OUP) ; 2020
    In:  Journal of Crohn's and Colitis Vol. 14, No. 4 ( 2020-05-21), p. 490-500
    Details
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 14, No. 4 ( 2020-05-21), p. 490-500
    Abstract: We evaluated the cost-effectiveness of early [≤2 years after diagnosis] compared with late or no biologic initiation [starting biologics & gt;2 years after diagnosis or no biologic use] for adults with Crohn’s disease in Switzerland. Methods We developed a Markov cohort model over the patient’s lifetime, from the health system and societal perspectives. Transition probabilities, quality of life, and costs were estimated using real-world data. Propensity score matching was used to ensure comparability between patients in the early [intervention] and late/no [comparator] biologic initiation strategies. The incremental cost-effectiveness ratio [ICER] per quality-adjusted life year [QALY] gained is reported in Swiss francs [CHF]. Sensitivity and scenario analyses were performed. Results Total costs and QALYs were higher for the intervention [CHF384 607; 16.84 QALYs] compared with the comparator [CHF340 800; 16.75 QALYs] strategy, resulting in high ICERs [health system: CHF887 450 per QALY; societal: CHF449 130 per QALY]. In probabilistic sensitivity analysis, assuming a threshold of CHF100 000 per QALY, the probability that the intervention strategy was cost-effective was 0.1 and 0.25 from the health system and societal perspectives, respectively. In addition, ICERs improved when we assumed a 30% reduction in biologic prices [health system: CHF134 502 per QALY; societal: intervention dominant] . Conclusions Early biologic use was not cost-effective, considering a threshold of CHF100 000 per QALY compared with late/no biologic use. However, early identification of patients likely to need biologics and future drug price reductions through increased availability of biosimilars may improve the cost-effectiveness of an early treatment approach.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    URL: Article
    DOI: 10.1093/ecco-jcc/jjz169
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2389631-0
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