The Use of Cellomics to Study Enterocyte Cytoskeletal Proteins in Coeliac Disease Patients

Coeliac disease is characterised by inflammation of small intestinal mucosa accompanied by abnormal villous architecture. It is now accepted that some patients with positive coeliac serology tests may have minor mucosal lesions that may not be apparent on routine histopathological analysis. The aim of the study was to perform detailed examination of enterocyte morphology and cytoskeletal structures using a high content analysis technology. Duodenal biopsies from 14 untreated and 10 treated coeliac patients and from 20 non-coeliac controls were examined. Tissue sections from six patients (study group subjects) before and after the development of gluten-sensitive enteropathy were also investigated. Immunohistochemical studies were performed on paraffin-embedded sections using an anti-α-tubulin antibody. Significant differences in enterocyte morphology and intracellular cytoskeletal structures were demonstrated in patients with proven coeliac disease and in the study group subjects. These changes were present in study group biopsies before evidence of enteropathy, as assessed by routine microscopy. This is the first study to demonstrate detailed characteristics of enterocyte morphology in coeliac patients using a high content analysis approach. The use of this technology allows a quantitative analysis of enterocyte intracellular structures from routine biopsy material and permits detection of subtle changes that precede the characteristic histological lesion

The European internet-based patient and research database for primary immunodeficiencies: results 2006-2008

Primary immunodeficiencies (PID) are rare diseases; therefore transnational studies are essential to maximize the scientific outcome and to improve diagnosis and therapy. In order to estimate the prevalence of PID in Europe as well as to establish and evaluate harmonized guidelines for the diagnosis and treatment of PID, the European Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. This database is a platform for epidemiological analyses as well as the development of new diagnostic and therapeutic strategies and the identification of novel disease-associated genes. Within 4 years, 7430 patients from 39 countries have been documented in the ESID database. Common variable immunodeficiency (CVID) represents the most common entity, with 1540 patients or 20.7% of all entries, followed by isolated immunoglobulin (Ig)G subclass deficiency (546 patients, 7.4%). Evaluations show that the average life expectancy for PID patients varies from 1 to 49 years (median), depending on the type of PID. The prevalence and incidence of PID remains a key question to be answered. As the registration progress is far from finished we can only calculate minimum values for PID, with e.g. France currently showing a minimum prevalence of 3.72 patients per 100,000 inhabitants. The most frequently documented permanent treatment is immunoglobulin replacement; 2819 patients (42% of all patients alive) currently receive this form of treatment

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria

Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19. Materials and Methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19. Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation

Contribution of Human Muscle-Derived Cells to Skeletal Muscle Regeneration in Dystrophic Host Mice

Background: Stem cell transplantation is a promising potential therapy for muscular dystrophies, but for this purpose, the cells need to be systemically-deliverable, give rise to many muscle fibres and functionally reconstitute the satellite cell niche in the majority of the patient's skeletal muscles. Human skeletal muscle-derived pericytes have been shown to form muscle fibres after intra-arterial transplantation in dystrophin-deficient host mice. Our aim was to replicate and extend these promising findings.Methodology/Principal Findings: Isolation and maintenance of human muscle derived cells (mdcs) was performed as published for human pericytes. Mdscs were characterized by immunostaining, flow cytometry and RT-PCR; also, their ability to differentiate into myotubes in vitro and into muscle fibres in vivo was assayed. Despite minor differences between human mdcs and pericytes, mdscs contributed to muscle regeneration after intra-muscular injection in mdx nu/nu mice, the CD56+ sub-population being especially myogenic. However, in contrast to human pericytes delivered intra-arterially in mdx SCID hosts, mdscs did not contribute to muscle regeneration after systemic delivery in mdx nu/nu hosts.Conclusions/Significance: Our data complement and extend previous findings on human skeletal muscle-derived stem cells, and clearly indicate that further work is necessary to prepare pure cell populations from skeletal muscle that maintain their phenotype in culture and make a robust contribution to skeletal muscle regeneration after systemic delivery in dystrophic mouse models. Small differences in protocols, animal models or outcome measurements may be the reason for differences between our findings and previous data, but nonetheless underline the need for more detailed studies on muscle-derived stem cells and independent replication of results before use of such cells in clinical trials

Haemophilus influenzae pneumonia and immunodeficiency in association with thymomaâA presentation of Good's Syndrome

Introduction: Good's Syndrome is a rare cause of immunodeficiency associated with thymoma. Patients with this syndrome are prone to infections with encapsulated microorganisms. The diagnosis may be delayed for a considerable time period even after the thymectomy. Case presentation: We describe the case of a 70-year-old woman with a background of thymec-tomy who presented with pneumonia and gram negative sepsis. Haemophilus influenzae was found in blood cultures. Moreover, there was evidence of impaired B and T cell immunity con-sistent with Good's Syndrome. She was commenced on immunoglobulin replacement following treatment of sepsis and remains well 18 months after the initial presentation. Conclusion: This case illustrates the importance of considering Good's Syndrome in the con-text of pneumonia and immunodeficiency associated with encapsulated organisms such as Haemophilus influenzae. This clinical entity is associated with a significant mortality and should be considered as a cause of immunodeficiency even years after thymectomy. Resumo: Introdução: A Síndrome de Good é uma causa rara da imunodeficiência associada ao timoma. Os pacientes com esta síndrome são propensos a infecções por microrganismos encapsulados. O diagnóstico pode ser atrasado por bastante tempo, mesmo após a timectomia. Apresentação do Caso: Descrevemos o caso de uma mulher de 70 anos com antecedentes de timectomia, que apresentava pneumonia e sepsis por agente gram negativo. O Haemophilus influenzae foi isolado em hemoculturas. Além disso, evidência de alterações da imunidade celular B e T, consistente com a Síndrome de Good. A doente iniciou terapêutica de substituição com imunoglobulina seguida de tratamento da sepsis e continua bem 18 meses após a apresentação inicial. Conclusão: Este caso ilustra a importância de considerar a Síndrome de Good no contexto da pneumonia e imunodeficiência associadas a organismos encapsulados, como Haemophilus influenzae. Esta entidade clínica está associada a uma mortalidade significativa e deve ser considerada como uma causa de imunodeficiência mesmo anos depois da timectomia. Keywords: Respiratory infections, Immunodeficiency, Thymoma, Palavras chave: Infecções respiratórias, Imunodeficiência, Timom

Management of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in the Pan-Arab Region: Consensus Recommendations from a Multidisciplinary Expert Working Group

Osama Marglani,1,2 Rashid Al Abri,3 Mona Al Ahmad,4 Saad Alsaleh,5 Mohamed Abuzakouk,6 Reda Kamel7 1Department of Ophthalmology, and Otolaryngology, Head and Neck Surgery, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Surgery, King Faisal Specialist Hospital & Research Center, Jeddah, Saudi Arabia; 3Sultan Qaboos University Hospital, Muscat, Oman; 4Al-Rashed Allergy Centre, Kuwait, State of Kuwait; 5Rhinology and Endoscopic Skull Base Surgery Division, Otolaryngology – Head and Neck Surgery Department, King Saud University, Riyadh, Saudi Arabia; 6Department of Allergy and Immunology, Respiratory Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates; 7Department of Otorhinolaryngology, Cairo University, Cairo, EgyptCorrespondence: Osama Marglani, Department of Surgery, King Faisal Specialist Hospital & Research Center, Jeddah, 23431, Saudi Arabia, Email [email protected]: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic and often debilitating inflammatory condition of the nasal and paranasal tissues. An expert panel of specialists from the Gulf region (the Kingdom of Saudi Arabia, Kuwait, Oman and the United Arab Emirates) and from Egypt gathered to evaluate existing guidance and develop regional guidance on the management of CRSwNP through a consensus approach. The present article presents the main observations and recommendations from this panel. CRSwNP diagnosis requires the presence of bilateral, endoscopically visualized polyps in the middle meatus (via nasal endoscopy or CT). In most patients, CRSwNP is mediated through predominantly type 2 inflammatory processes and is often observed in patients with asthma and other allergic disease. While many patients respond to medical treatment (principally topical irrigation and intranasal corticosteroids, and adjunctive short-term use of systemic corticosteroids), clinical management of CRSwNP is challenging, and a multidisciplinary approach for complete evaluation and treatment is recommended. Patients with more severe/uncontrolled disease (despite adequate medical therapies) require a complete endoscopic sinus surgery (ESS), although outcomes can be unsatisfactory, and further revision surgery is common. Biological therapies targeting underlying inflammatory processes offer additional, effective treatment options for those patients with persistent symptoms despite complete ESS, and also in those patients where surgery may be contraindicated.Keywords: chronic rhinosinusitis with nasal polyposis, CRSwNP, type 2 inflammation, biologic