Summary
The antigenic specificity of T cells occurs via generation and rearrangement of different gene segments producing a functional T cell receptor (TCR). High‐throughput sequencing (HTS) allows ...in‐depth assessment of TCR repertoire patterns. There are limited data concerning whether TCR repertoires are altered in inflammatory bowel disease. We hypothesized that pediatric ulcerative colitis (UC) patients possess unique TCR repertoires, resulting from clonotypical expansions in the gut. Paired blood and rectal samples were collected from nine newly diagnosed treatment‐naive pediatric UC patients and four healthy controls. DNA was isolated to determine the TCR‐β repertoire by HTS. Significant clonal expansion was demonstrated in UC patients, with inverse correlation between clinical disease severity and repertoire diversity in the gut. Using different repertoire variables in rectal biopsies, a clear segregation was observed between patients with severe UC, those with mild–moderate disease and healthy controls. Moreover, the overlap between autologous blood–rectal samples in UC patients was significantly higher compared with overlap among controls. Finally, we identified several clonotypes that were shared in either all or the majority of UC patients in the colon. Clonal expansion of TCR‐β‐expressing T cells among UC patients correlates with disease severity and highlights their involvement in mediating intestinal inflammation.
Using next‐generation sequencing of the TCR‐β we demonstrate altered repertoire features in pediatric patients with newly diagnosed ulcerative colitis. We show clonal expansion of specific clonotypes that correlates with disease activity in ulcerative colitis, highlighting their involvement in mediating intestinal inflammation.
Here, we describe that microenvironmental IL-1β and, to a lesser extent, IL-1α are required for in vivo angiogenesis and invasiveness of different tumor cells. In IL-1β knockout (KO) mice, local ...tumor or lung metastases of B16 melanoma cells were not observed compared with WT mice. Angiogenesis was assessed by the recruitment of blood vessel networks into Matrigel plugs containing B16 melanoma cells; vascularization of the plugs was present in WT mice, but was absent in IL-1β KO mice. The addition of exogenous IL-1 into B16-containing Matrigel plugs in IL-1β KO mice partially restored the angiogenic response. Moreover, the incorporation of IL-1 receptor antagonist to B16-containing plugs in WT mice inhibited the ingrowth of blood vessel networks into Matrigel plugs. In IL-1α KO mice, local tumor development and induction of an angiogenic response in Matrigel plugs was less pronounced than in WT mice, but significantly higher than in IL-1β KO mice. These effects of host-derived IL-1α and IL-1β were not restricted to the melanoma model, but were also observed in DA/3 mammary and prostate cancer cell models. In addition to the in vivo findings, IL-1 contributed to the production of vascular endothelial cell growth factor and tumor necrosis factor in cocultures of peritoneal macrophages and tumor cells. Host-derived IL-1 seems to control tumor angiogenesis and invasiveness. Furthermore, the anti-angiogenic effects of IL-1 receptor antagonist, shown here, suggest a possible therapeutic role in cancer, in addition to its current use in rheumatoid arthritis.
Summary
The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely ...unrecognized, including in high‐risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.
Hepatitis A is one of the most common vaccine-preventable infectious diseases in the world. Effective vaccines against hepatitis A have been available since 1992, and they provide long-term immunity ...against the infection. However, there is no worldwide consensus on how long protection will last or whether there will be a need for hepatitis A virus (HAV) booster vaccinations in the future. In most countries, booster-vaccination policy is guided by manufacturers' recommendations, national authorities, or both. In June, 2002, a panel of international experts met to review the long-term immunogenicity and protection conferred by HAV vaccine in different population groups. Data have shown that after a full primary vaccination course, protective antibody amounts persist beyond 10 years in healthy individuals, and underlying immune memory provides protection far beyond the duration of anti-HAV antibodies. The group concluded that there is no evidence to lend support to HAV booster vaccination after a full primary vaccination course in a healthy individual. However, further investigations are needed before deciding if boosters can be omitted in special patient-groups.
For the first time a global meeting on hepatitis A virus (HAV) infection as vaccine preventable disease was organized at the end of 2007. More than 200 experts from 46 countries gathered to ...investigate the changing global HAV epidemiology reflecting the increasing numbers of persons at risk for severe clinical disease and mortality from HAV infection. The benefits of childhood and adult hepatitis A (HepA) vaccination strategies and the data needed by individual countries and international health organizations to assess current HepA prevention strategies were discussed. New approaches in preventing HAV infection including universal HepA vaccination were considered. This introductory paper summarizes the major findings of the meeting and describes the changing epidemiology of HAV infections and the impact of HepA vaccination strategies in various countries. Implementation of HepA vaccination strategies should take into account the level of endemicity, the level of the socio‐economic development and sanitation, and the risk of outbreaks. A stepwise strategy for introduction of HepA universal immunisation of children was recommended. This strategy should be based on accurate surveillance of cases and qualitative documentation of outbreaks and their control, secure political support on the basis of high‐quality results, and comprehensive cost‐effectiveness studies. The recognition of the need for increased global attention towards HepA prevention is an important outcome of this meeting.
Abstract
Objective
We aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn’s disease CD.
Methods
We formed 10 working groups and ...formulated 17 PICO-structured clinical questions Patients, Intervention, Comparator, and Outcome. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached ≥ 80% agreement and were retained.
Results
We established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor TNF agents in combination with an immunomodulator. Therapeutic drug monitoring to guide treatment changes is recommended over empirically escalating anti-TNF dose or switching therapies. Patients with low-risk luminal CD should be induced with exclusive enteral nutrition EEN, or with corticosteroids when EEN is not an option, and require immunomodulator-based maintenance therapy. Favourable outcomes rely on close monitoring of treatment response, with timely adjustments in therapy when treatment targets are not met. Serial faecal calprotectin measurements or small bowel imaging ultrasound or magnetic resonance enterography are more reliable markers of treatment response than clinical scores alone.
Conclusions
We present state-of-the-art guidance on the medical treatment and long-term management of children and adolescents with CD.
New parameters such as the presence of portal vein thrombosis, unifocal or multifocal tumours, elevated alpha fetoprotein (AFP) levels, and performance status have been proposed for inclusion in ...staging systems for HCC patients. Since 1998, three new scoring systems have been proposed by European groups for evaluation of HCC candidates for treatment, namely the CLIP score 4 (Italian investigators for cancer of the liver program), the BCLC score 5 (Barcelona clinic liver cancer staging), and the French prognostic classification for predicting survival in HCC patients. 6 The BCLC group introduced clinically relevant portal hypertension as a new prognostic parameter for HCC staging while the French scoring system includes elevated alkaline phosphatase and AFP levels (also used in the CLIP score) among the factors for evaluation of prognosis.
The Viral Hepatitis Prevention Board (VHPB) convened a meeting of international experts from the public and private sectors in order to review and evaluate the epidemiology of blood-borne infections ...in healthcare workers, to evaluate the transmission of hepatitis B and C viruses as an occupational risk, to discuss primary and secondary prevention measures and to review recommendations for infected healthcare workers and (para)medical students. This VHPB meeting outlined a number of recommendations for the prevention and control of viral hepatitis in the following domains: application of standard precautions, panels for counselling infected healthcare workers and patients, hepatitis B vaccination, restrictions on the practice of exposure-prone procedures by infected healthcare workers, ethical and legal issues, assessment of risk and costs, priority setting by individual countries and the role of the VHPB. Participants also identified a number of terms that need harmonisation or standardisation in order to facilitate communication between experts.
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