Detection of Colorectal Neoplasia in a Cohort Before and After the Change of Fecal Occult Blood Test in a French Colorectal Cancer Screening Program.

OBJECTIVE: To estimate the change in the participation rate and the change in neoplasia incidence before and after the change of the Fecal Occult Blood Test (FOBT) in the cohort included in the Colorectal Cancer Screening Program (CRCSP). METHODS: Cohort of 279,210 people, aged 50-74 years, invited at least once before 2009, to participate in a CRCSP campaign. The participation rate and the cumulative neoplasia incidence were described on 4 campaigns (≤2008, 2009-2010, 2011-2012 and 2013-2014) with a Guaiac FOBT (gFOBT) and a first campaign (2015-2016) with a Fecal Immunochemical Test (FIT). The cumulative incidence was estimated by the actuarial method and its confidence interval by the Greenwood method. RESULTS: The participation rate decreased from 32.7% (first gFOBT-campaign) to 24.4% (fourth gFOBT-campaign) then, made a significant bound in the FIT-campaign (28.4%; p < 0.001). 35.4% of the 965 high-risk-polyps screened in this cohort were detected in the FIT-campaign. CRC incidence gradually decreased from 0.4 to 0.1/1000 person-years from the first to the fourth gFOBT-campaign before reaching a bound to 0.4/1000 person-years in the FIT-campaign. CONCLUSION: Although it was still below the minimum European target (45%), the participation rate has increased between the last gFOBT-campaign and FIT-campaign, justifying the impact of promotional campaigns and the acceptance of the new test by people and GPs. A decline in the neoplasia incidence was observed between the initial and the fourth gFOBT-campaign. The change from gFOBT to FIT between the fourth and fifth campaigns, was associated with a significant increase in detection of neoplasia.

Pattern of inpatient referrals to a drug allergy unit in Kuwait.

SUMMARY: Introduction. There is no information regarding the pattern of inpatient referrals to drug allergy units in Kuwait. Objectives. The main goal of this study is to clarify the pattern of inpatient referrals to a drug allergy unit in terms of incidence, drugs implicated and allergy evaluation outcomes in comparison with studies in other countries. Patients and Methods. A retrospective chart review of inpatient drug allergy consultations at Al-Rashed Allergy Center over a 3-year period was performed. Results. A total of 51 patients were referred for drug allergy consultations, with an estimated incidence of reported drug allergy among inpatients of 0.008%. There is an increasing trend of referrals from public health centres located in proximity to Al-Rashed Allergy Center. Beta-lactams, contrast media, and general anaesthetics were the most common drugs leading to referrals. In total, 30% of patients were diagnosed with an allergy to the offending drug after a full allergy evaluation. Conclusion. Inpatient drug allergy referrals are highly underreported in Kuwait.

[Short history of laboratory diagnostics of allergy in Hungary, current possibilities and future perspectives]. / Az allergia laboratóriumi diagnosztikájának rövid hazai története, a jelen lehetoségei és a jövo perspektívája.

Up to know the indications for the optimal applications of laboratory diagnosis of allergic diseases have become widely known. Measurements of allergy specific IgE and various tests of cell mediated immunity are included in the practice. It can be stated that measurements of total serum IgE and allergen specific IgE (kU/l and RAST classes) can be maintained further in the Hungarian practice with the expected continuous participation of all laboratories in the external quality control program (QualiCont). However, it is also apparent that regional introduction of the urgent "molecular (component) based allergy diagnostics" has become necessary for efficient allergen specific immunotherapy in Hungary. In cases of the allergen specific cell mediated immunologic reactions, allergen induced cell proliferation and cytokine release measurements are recommended. However, it is also obvious that application of these measurements in clinical practice need correct financial support from health care authorities.

The future of immunoimaging--deeper, bigger, more precise, and definitively more colorful.

Immune cells are thoroughbreds, moving farther and faster and surveying more diverse tissue space than their nonhematopoietic brethren. Intravital 2-photon microscopy has provided insights into the movements and interactions of many immune cell types in diverse tissues, but more information is needed to link such analyses of dynamic cell behavior to function. Here, we describe additional methods whose application promises to extend our vision, allowing more complete, multiscale dissection of how immune cell positioning and movement are linked to system state, host defense, and disease.

Immunodiagnosis of sheep infections with Echinococcus granulosus: in 35 years where have we come?

W. K. Yong and D. D. Heath published in 1979 a seminal paper in the first issue of Parasite immunology describing their efforts to determine whether the arc 5 precipitin band, formed when test human serum is reacted against electrophoresed hydatid cyst fluid antigen, would be a suitable immunodiagnostic test for the identification of sheep infected with Echinococcus granulosus. Although they found antibodies to arc 5 in the sera of hydatid-infected sheep, the sera of some sheep harbouring Taenia ovis and T. hydatigena also precipitated the hydatid cyst fluid arc 5 antigen, so they concluded arc 5 antibodies were not suitable for the specific immunodiagnosis of E. granulosus infection in sheep in New Zealand. Subsequent work has shown that the existence of multiple infections with different taeniid species, antigenic cross-reactivity between these related parasites and the low level of specific antibody response to infection continue to hinder efforts to improve the diagnosis of hydatid infection in sheep and other natural intermediate hosts, thereby preventing the development of any practical test. In particular, the poor antibody response of ruminants to naturally acquired hydatid infection may prove an insurmountable barrier in future efforts to develop a reliable and accurate immunological test.

[What place and what future for the pathology of infectious and tropical diseases in France?]. / Quelle place et quel avenir pour l'anatomo-cyto-pathologie des maladies infectieuses et tropicales en France?

The management of tissues and cellular samples by the pathologists in the infectious and tropical diseases pathology field in 2014 needs a strong knowledge of both morphological and molecular domains which includes the good control: (i) of the taxonomy of infectious and tropical diseases pathology leading to the pathogens identification and (ii) of the ancillary methods which can be used in fixed samples in order to detect or better identify these pathogens. There is a recent paradox in France concerning the frequency of infectious diseases to be diagnosed in pathology laboratories and the progressive loss of pathologist's expertise in this domain. Different reasons could explain this statement including the omnipresence of the tumour lesions to be managed in a pathology laboratory as well as the recent constraints associated with the different biomarkers that are mandatory to be detected by immunohistochemistry and/or by molecular biology. Even if the microbiologists play a pivotal role for identifying the different pathogens as well as for the assessment of their sensitivity to the anti-microbial drugs, a large number of infectious diseases can be diagnosed only on fixed tissue and/or cells by the pathologists. The purpose of this review is to describe the current and future issues of infectious and tropical diseases diagnoses in pathology laboratories, in particular in France.

Recent advances in diagnosis and therapy of allergic rhinitis and asthma in childhood.

Some of the most recent advances in the diagnosis and treatment of childhood asthma and allergies are here reviewed. New perspectives have been opened by in vitro diagnostic tests for allergies based on a molecular approach and novel approaches to in vivo tests (SPT or FE(NO)). A better characterization of the patients is opening new classifications of allergic asthma and rhinitis phenotypes, which allow personalizing management disease programs and targeting pharmacotherapy. Educational programs and better communication are improving awareness and compliance with medical prescriptions and adherence to guidelines. Increasing information is being acquired on the mechanisms, efficacy and safety profiles of anti-asthma and anti-allergic drugs, including antihistamines, inhaled corticosteroids, long acting beta agonists, antibiotics, anti-IgE antibodies. Progress in biotechnologies is fostering new approaches to allergen-specific immunotherapy (subcutaneous, sublingual) concerning the quality, mechanisms, efficacy and safety of allergen products.

[What's new in immune-mediated neuropathies?]. / Actualités des neuropathies dysimmunitaires (hors traitement).

Many papers have been published in the field of immune-mediated neuropathies in 2010. Various topics have been covered: diagnostic criteria and clinical forms, pain and its risk factors, clinical evaluation and new immunological markers. Additionally, as nerve biopsy is still useful for evaluating patients with peripheral neuropathy, French and international guidelines have been published. This paper aims to summarize recent discoveries in the field of immune-mediated neuropathies.

Classification of lymphoid neoplasms: the microscope as a tool for disease discovery.

In the past 50 years, we have witnessed explosive growth in the understanding of normal and neoplastic lymphoid cells. B-cell, T-cell, and natural killer (NK)-cell neoplasms in many respects recapitulate normal stages of lymphoid cell differentiation and function, so that they can be to some extent classified according to the corresponding normal stage. Likewise, the molecular mechanisms involved the pathogenesis of lymphomas and lymphoid leukemias are often based on the physiology of the lymphoid cells, capitalizing on deregulated normal physiology by harnessing the promoters of genes essential for lymphocyte function. The clinical manifestations of lymphomas likewise reflect the normal function of lymphoid cells in vivo. The multiparameter approach to classification adopted by the World Health Organization (WHO) classification has been validated in international studies as being highly reproducible, and enhancing the interpretation of clinical and translational studies. In addition, accurate and precise classification of disease entities facilitates the discovery of the molecular basis of lymphoid neoplasms in the basic science laboratory.

Advances in the diagnosis of tuberculosis.

Tuberculosis ranges among the leading causes of morbidity and mortality worldwide. A diagnostic approach to a patient with possible tuberculosis includes a detailed medical history and clinical examination as well as radiological, microbiological, immunological, molecular-biological and histological investigations, where available. Recently, important advances have been achieved in these fields that have led to substantial improvements in the accuracy and the timing of the diagnosis of tuberculosis. Novel methods allow for a better identification of latently infected individuals who are at risk of developing active tuberculosis, they also offer the possibility for a rapid diagnosis of active tuberculosis in patients with negative sputum smears for acid-fast bacilli and enable prompt identification of drug-resistant strains of Mycobacterium tuberculosis directly from respiratory specimen with a high accuracy. In addition, promising methods that will further optimize the diagnosis of tuberculosis are under development. In the future, therapeutic interventions based on the results of novel diagnostic procedures can be made earlier leading to improvements in patient care.

Increased levels of soluble CD226 in sera accompanied by decreased membrane CD226 expression on peripheral blood mononuclear cells from cancer patients.

BACKGROUND: As a cellular membrane triggering receptor, CD226 is involved in the NK cell- or CTL-mediated lysis of tumor cells of different origin, including freshly isolated tumor cells and tumor cell lines. Here, we evaluated soluble CD226 (sCD226) levels in sera, and membrane CD226 (mCD226) expression on peripheral blood mononuclear cells (PBMC) from cancer patients as well as normal subjects, and demonstrated the possible function and origin of the altered sCD226, which may provide useful information for understanding the mechanisms of tumor escape and for immunodiagnosis and immunotherapy. RESULTS: Soluble CD226 levels in serum samples from cancer patients were significantly higher than those in healthy individuals (P < 0.001), while cancer patients exhibited lower PBMC mCD226 expression than healthy individuals (P < 0.001). CD226-Fc fusion protein could significantly inhibit the cytotoxicity of NK cells against K562 cells in a dose-dependent manner. Furthermore, three kinds of protease inhibitors could notably increase mCD226 expression on PMA-stimulated PBMCs and Jurkat cells with a decrease in the sCD226 level in the cell culture supernatant. CONCLUSION: These findings suggest that sCD226 might be shed from cell membranes by certain proteases, and, further, sCD226 may be used as a predictor for monitoring cancer, and more important, a possible immunotherapy target, which may be useful in clinical application.

[Prospects for using antigenic nanosystems in the diagnosis and treatment of inflammatory rheumatic diseases].

AIM: To study whether immobilized antigenic nanosystems (ANS) may be designed on the basis of antigens of varying chemical nature to identify and to remove specific antibodies (Ab) from the blood of patients with systemic lupus erythematosus (SLE). SUBJECTS AND METHODS: Sixty patients with the diagnosis of SLE verified by the 1997 American College of Rheumatology criteria and 30 apparently healthy individuals were followed up. The levels of Ab to catalase (Cat), xanthine oxidase (XO), and cardiolipin (CL) were measured by enzyme immunoassay, by applying the respective ANS as an antigenic matrix. RESULTS: There was a significant relationship of the levels of Ab to Cat and XO to the activity of SLE. It was shown that Ab to Cat and XO could affect the functional activity of serum enzymes. The level of Ab to CL in patients with SLE was found to depend on two parameters - the intensity of the disease and the presence of antiphospholipid syndrome; acute cerebral circulatory disorder and thrombocytopenia were observed to have a significant unidirectional impact on the level of Ab to CL. Immobilized CL-based ANSs were effective in eliminating Ab to CL from the whole blood of patients with SLE, without resulting in a significant hemolysis of blood corpuscles and in a reduction of total protein concentrations. CONCLUSION: The development and introduction of preventive methods for the early diagnosis of SLE may be extended, by using ANS based on Cat, XO, and CL antigen. The designing and putting into practice novel ANS-based hemosorbents may allow immunosorption to occupy a prominent place in the pathogenetic therapy of inflammatory autoimmune diseases.

The Future of Clinical Immunology Laboratory Testing.

For decades, autoantibody detection has comprised the bulk of clinical laboratory immunology. However, most immune disorders are caused by imbalances in both humoral and cellular immunity. Our knowledge of the immune system has grown exponentially, resulting in new treatment paradigms in immunology. Extensive functional characterization of lymphocyte subsets is routinely carried out in a research laboratories, facilitated by the emergence of high-dimensional analysis technologies for low cell numbers. It will not be long before these approaches enter the diagnostic realm. This chapter outlines emerging trends in laboratory immunology testing with a focus on deep immune profiling or high-dimensional testing modalities.

Autoimmunity in psychotic disorders. Where we stand, challenges and opportunities.

Psychotic disorders are debilitating mental illnesses associated with abnormalities in various neurotransmitter systems. The development of disease-modifing therapies has been hampered by the mostly unknown etiologies and pathophysiologies. Autoantibodies against several neuronal antigens are responsible for autoimmune encephalitis. These autoantibodies disrupt neurotransmission within the brain, resulting in a wide range of psychiatric and neurologic manifestations, including psychosis. The overlap of symptoms of autoimmune encephalitis with psychotic disorders raised the question as to whether autoantibodies against a number of receptors, ion channel and associated proteins could ultimately be responsible for some forms of psychosis. Here we review our current knowledge, on antibody mediated autoimmunity in psychotic disorders, the different diagnostic methods and their limitations, as well as on varying therapeutic approaches targeting the immune system.

Moving Forward: Recent Developments for the Ferret Biomedical Research Model.

Since the initial report in 1911, the domestic ferret has become an invaluable biomedical research model. While widely recognized for its utility in influenza virus research, ferrets are used for a variety of infectious and noninfectious disease models due to the anatomical, metabolic, and physiological features they share with humans and their susceptibility to many human pathogens. However, there are limitations to the model that must be overcome for maximal utility for the scientific community. Here, we describe important recent advances that will accelerate biomedical research with this animal model.