Direct targeting of FOXP3 in Tregs with AZD8701, a novel antisense oligonucleotide to relieve immunosuppression in cancer.

Background: The Regulatory T cell (Treg) lineage is defined by the transcription factor FOXP3, which controls immune-suppressive gene expression profiles. Tregs are often recruited in high frequencies to the tumor microenvironment where they can suppress antitumor immunity. We hypothesized that pharmacological inhibition of FOXP3 by systemically delivered, unformulated constrained ethyl-modified antisense oligonucleotides could modulate the activity of Tregs and augment antitumor immunity providing therapeutic benefit in cancer models and potentially in man.

The Impact of Pre-existing Comorbidities and Therapeutic Interventions on COVID-19.

Evidence from the global outbreak of SARS-CoV-2 has clearly demonstrated that individuals with pre-existing comorbidities are at a much greater risk of dying from COVID-19. This is of great concern for individuals living with these conditions, and a major challenge for global healthcare systems and biomedical research. Not all comorbidities confer the same risk, however, many affect the function of the immune system, which in turn directly impacts the response to COVID-19.

Probabilistic mapping of language networks from high frequency activity induced by direct electrical stimulation.

Direct electrical stimulation (DES) at 50 Hz is used as a gold standard to map cognitive functions but little is known about its ability to map large-scale networks and specific subnetwork. In the present study, we aim to propose a new methodological approach to evaluate the specific hypothesis suggesting that language errors/dysfunction induced by DES are the result of large-scale network modification rather than of a single cortical region, which explains that similar language symptoms may be observed after stimulation of different cortical regions belonging to this network. We retrospectively examined 29 patients suffering from focal drug-resistant epilepsy who benefitted from stereo-electroencephalographic (SEEG) exploration and exhibited language symptoms during a naming task following 50 Hz DES.

Recent Advancements and Applications of Human Immune System Mice in Preclinical Immuno-Oncology.

Significant advances in immunotherapies have resulted in the increasing need of predictive preclinical models to improve immunotherapeutic drug development, treatment combination, and to prevent or minimize toxicity in clinical trials. Immunodeficient mice reconstituted with human immune system (HIS), termed humanized mice or HIS mice, permit detailed analysis of human immune biology, development, and function. Although this model constitutes a great translational model, some aspects need to be improved as the incomplete engraftment of immune cells, graft versus host disease and the lack of human cytokines and growth factors.

Extracellular vesicles induce minimal hepatotoxicity and immunogenicity.

Extracellular vesicles (EVs) mediate cellular communication through the transfer of active biomolecules, raising interest in using them as biological delivery vehicles for therapeutic drugs. For drug delivery applications, it is important to understand the intrinsic safety and toxicity liabilities of EVs. Nanoparticles, including EVs, typically demonstrate significant accumulation in the liver after systemic administration in vivo.

Pigeon tick bite: A neglected cause of idiopathic nocturnal anaphylaxis.

Anaphylaxis is a serious systemic allergic reaction with rapid onset and potentially life-threatening. We report in detail a case of severe nocturnal anaphylaxis due to pigeon tick bite showing the diagnostic value of the extract and the recombinant allergen in the diagnostic procedures (basophil activation test, IgE immunoblot, and experimental ImmunoCAP). Apart from the presented case, we describe that during the last 10 years, we have collected 28 cases of allergy to Argas reflexus from several European countries.

The prevalence of sensitization to lupin flour in France and Belgium: a prospective study in 5,366 patients, by the Allergy Vigilance Network.

Objectives: To determine the prevalence of sensitization to lupin flour in patients consulting allergists, in order to evaluate the risk of primary and secondary allergies to lupin.

Methods: A prospective study carried out by members of the Allergy Vigilance Network, using prick-tests with a commercial lupin flour extract in patients with various allergic symptoms. The study design classified patients into four groups: peanut allergy, current atopic disease, latent atopy, no atopy.

[Allergy and fishing activities].

Diagnosis of allergy diseases is at first linked to a detailed history, in which professional activities as well as the environment take an important place. Fishing activity as well as aquarium-related activities may be the origin of a symptomatology which is, often IgE-mediated, respiratory and skin localised: the responsible agents are most often insects in their larval form, crustaceans and worms.

[Pulmonary alveolar proteinosis].

Pulmonary alveolar proteinosis (PAP) is a rare, diffuse infiltrative lung disease of unknown etiology characterized by accumulation of abnormal lung surfactant in the alveoli and distal airways. Although it was first described in 1958, few large scale studies have been published. The diagnosis is conventionally based on lung biopsy and the value of less invasive procedures such as bronchoalveolar lavage (BAL) remains controversial.

Frequency of cystic fibrosis transmembrane conductance regulator gene mutations and 5T allele in patients with allergic bronchopulmonary aspergillosis.

Study Objective: To assess the frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in patients with allergic bronchopulmonary aspergillosis (ABPA).

Design: Case-control study. All subjects in the study were screened for the presence of 13 mutations in the CFTR gene (R117H, 621 + 1G(-)>T, R334 W, Delta F508, Delta I507, 1717-1G(-)>A, G542X, R553X, G551D, R1162X, 3849 + 10kbC(-)>T, W1282X, and N1303K).

[Diagnosis of intralobar pulmonary sequestration using helical computed tomography angiography: apropos of 3 patients].

Pulmonary sequestration is a rare congenital anomaly that consists of abnormal pulmonary tissue for which the arterial supply is usually derived from the aorta or its major branches. Considering clinical and anatomical aspects two types of sequestration, intralobar and extralobar, have been described. The definite diagnosis requires exact visualization of the anomalous feeding and draining vessels and this condition is essential when surgical treatment is necessary because of recurrent pulmonary infections.

Early effect of ultrarush venom immunotherapy on the IgG antibody response.

Background: We have previously shown in several allergy models that allergic and tolerance status with respect to allergens is associated with a somewhat different dominant specificity of IgG antibodies. The objective was to test this hypothesis in the compelling model of ultrarush venom immunotherapy (VIT), which induces clinical tolerance after only a few hours of treatment.

Methods: Antibody titers and specificity were evaluated through solid-phase ELISA using streptavidin-biotin technology in 12 patients allergic to wasp venom before and during the ultrarush procedure (at 12 h, 24 h, and 15 days).

[Diagnosis and staging using spiral computed tomography of an endobronchial carcinoid tumor].

The authors emphasize the effectiveness of spiral CT in the diagnosis of typical endobronchial carcinoid. The tumor was found in a 25-year-old man referred for evaluation of steroid-resistant asthma. Successful diagnosis and complete local staging of the right intermediate bronchus tumor were obtained by two successive single apnea spiral acquisitions: a high resolution series (HRCT) with Multiplanar Reconstruction (MPR) and 3D virtual endoscopic views was completed by a dynamic angiographic series (angio-CT) with multiplanar Maximal Intensity Projections (MIP).

[Alveolar proteinosis: signs and prognosis using high-resolution computed tomography in 5 patients].

Pulmonary alveolar proteinosis is a rare idiopathic diffuse airspace disease characterized by intraalveolar accumulation of large quantities of lipoproteinaceous material. The clinical presentation and course are variable and the definite diagnosis is made by biopsy or broncho-alveolar lavage (BAL) that also constitutes the unique and empiric treatment. We report the extremely typical HRCT features of the disease found in a series of five patients diagnosed in our institution over a ten-year period.

[Clinical pathological consultation: lung mass].

The anatomoclinical exercise consists in the discussion of the etiology of an isolated pulmonary nodule in an asymptomatic patient.

[Triton's malignant intrapulmonary tumor].

The authors report a case of an intrapulmonary tumour which on histological analysis was found to be a malignant Triton tumour after surgical excision. The tumours proved to be of nervous tissue origin and was a rare variant of malignant tumours of the surrounding of peripheral nerves with rhabdomyoblastic heterologous differentiation which is rarely described in the lungs. The characteristics of the tumour as well as therapeutic approaches are discussed followed by a review of the literature.

Modified antigenic reactivity of anti-phospholipase A2 IgG antibodies in patients allergic to bee venom: conversion with immunotherapy and relation to subclass expression.

Background: We have previously reported that, in addition to modifying IgG levels and subclass distributions, wasp venom immunotherapy (VIT) rapidly changes IgG antibody specificity.

Objectives: We investigated whether such a change can be documented in the IgG response to the major bee venom allergen, phospholipase A2 (PLA2), from patients allergic to bees treated with VIT; whether it is coupled to the shift in IgG subclass distribution (IgG4 predominance) usually observed during VIT; and whether it restores the specificity displayed by IgG antibodies from nonallergic individuals.

Methods: Antibody specificity was evaluated in 17 patients allergic to bee venom in competitive ELISAs by using streptavidin biotin technology.

Wasp venom immunotherapy changes IgG antibody specificity.

Background: The evolution of the IgG response during venom immunotherapy (VIT) has been previously investigated in terms of antibody titres and subclasses.

Objectives: The present work studied the evolution of IgG antibody fine specificity in wasp allergic patients treated with rush VIT.

Methods: Antibody specificity was evaluated in 51 wasp allergic patients in competitive ELISA using streptavidin biotin technology.

Pleural effusion during bromocriptine exposure in two patients with pre-existing asbestos pleural plaques: a relationship?

Two patients with pleural plaques developed pleural effusion and subsequent diffuse pleural fibrosis 50 and 39 yrs after their first exposure to asbestos. The diagnosis of benign asbestos pleural effusion was suggested, but the work-up finally suggested bromocriptine-induced pleural disease in both patients. These two cases illustrate that drug-induced pleural effusion is an important differential diagnosis of benign asbestos pleural effusion.

[Accelerated desensitization for hymenoptera venom allergy in 30 hours: efficacy and safety in 150 cases].

In this study, we performed 150 desensitizations in 139 Hymenoptera venom allergic patients (109 Yellow jacket allergic patients, 19 Honey bee allergic patients and 11 patients sensitized to both insects, who received a dual desensitization). We used a rush protocol, allowing injection of a total cumulated dose of 125,1 (Honey bee) to 175,1 (Yellow jacket) microgram of venom in 30 hours. Patients were hospitalized, with all emergency precautions for treating systemic reactions.

[Asthma to green coffee of environmental origin].

A case of rhinitis and environmental asthma caused by unroasted coffee has been reported in an adolescent living in a building in which there is an installation for roasting coffee. The diagnosis, suggested by the case history, is confirmed by the presence of specific IgE, by the positive result of the skin test using unroasted coffee extract and also of a broncho-provocation test entailing the manipulation of dust from the coffee roasting room. An amelioration of the room and work conditions is recommended.

[Azygos continuation of the inferior vena cava: apropos of 3 cases].

The authors report 3 cases of azygos continuation of the inferior vena cava. This congenital malformation is due to the atresia of inferior vena cava in the retrohepatic segment. The abnormalities encountered on the chest film are described.

[Pulmonary edema secondary to the intravenous administration of iodized contrast. A clinical case with high-resolution tomodensitometry studies].

Contrast media related reactions are numerous and of variable gravity. We report a case of pulmonary edema related to the intravenous administration of contrast media. Cardiogenic and non cardiogenic pulmonary edema are pathophysiologic possibilities.