Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: A seven case series

Background: Erdheim-Chester Disease (ECD), a non Langerhans' cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management. Objectives: The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients. Methods: Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients' illness. Results: Seven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions. Conclusions: ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling

Liposome-Mediated Cellular Delivery of Active gp91phox

International audienceBACKGROUND: Gp91(phox) is a transmembrane protein and the catalytic core of the NADPH oxidase complex of neutrophils. Lack of this protein causes chronic granulomatous disease (CGD), a rare genetic disorder characterized by severe and recurrent infections due to the incapacity of phagocytes to kill microorganisms. METHODOLOGY: Here we optimize a prokaryotic cell-free expression system to produce integral mammalian membrane proteins. CONCLUSIONS: Using this system, we over-express truncated forms of the gp91(phox) protein under soluble form in the presence of detergents or lipids resulting in active proteins with a "native-like" conformation. All the proteins exhibit diaphorase activity in the presence of cytosolic factors (p67(phox), p47(phox), p40(phox) and Rac) and arachidonic acid. We also produce proteoliposomes containing gp91(phox) protein and demonstrate that these proteins exhibit activities similar to their cellular counterpart. The proteoliposomes induce rapid cellular delivery and relocation of recombinant gp91(phox) proteins to the plasma membrane. Our data support the concept of cell-free expression technology for producing recombinant proteoliposomes and their use for functional and structural studies or protein therapy by complementing deficient cells in gp91(phox) protein

Cutaneous lesions of the external ear

Skin diseases on the external aspect of the ear are seen in a variety of medical disciplines. Dermatologists, othorhinolaryngologists, general practitioners, general and plastic surgeons are regularly consulted regarding cutaneous lesions on the ear

The gastrointestinal tract: properties and role in allogeneic hematopoietic stem cell transplantation

Introduction: The GI-tract is a major target for both the intensive chemo and/or radiotherapy conditioning as well as for GVHD and therefore is closely associated with transplant outcome. Apart from being a target, the GI-tract is also a mediator and therefore is also a key player of the pathogenetic process following allogeneic transplantation. Areas covered: The intestinal homeostasis is regulated through complicated interactions between the key players of this process which are the intestinal epithelium, the intestinal immune system, and the intestinal microbiota. A brief description of these elements, based on published english-language articles in PubMed, as well as their role during the process of allo-HSCT is discussed in this review. Expert commentary: Data on GI-tract properties suggest a central role for the intestine in regulation of immunity, both in healthy–steady state conditions and in pathological states such as during allo-HSCT. Given the fact that in the allogeneic transplant setting severe complications such as infections and GVHD are limiting this treatment modality, understanding the mechanisms that mediate intestinal homeostasis could lead to new preventive methods and improved outcomes. © 2017 Informa UK Limited, trading as Taylor & Francis Group

Telemedicine implementation in COVID-19 ICU: balancing physical and virtual forms of visibility

Objective: This case study examines the implementation of inpatient telemedicine in COVID-19 ICUs and explores the impact of shifting forms of visibility on the management of the unit, staff collaboration, and patient care. Background: The COVID-19 crisis drove healthcare institutions to rapidly develop new models of care based on integrating digital technologies for remote care with transformations in the hospital-built environment. The Sheba Medical Center in Israel created COVID-19 ICUs in an underground structure with an open-ward layout and telemedicine control rooms to remotely supervise, communicate, and support the operations in the contaminated zones. One unit has a physical visual connection between the control room and the contaminated zone through a window, while the other has only a virtual connection with digital technologies. Methods: The findings are based on semi-structured interviews with Sheba medical staff, telemedicine companies, and the architectural design team, and observations at the COVID units during March-August 2020. Results: The case study illustrates the implications of virtual and physical visibility on the management of the unit, staff collaboration, and patient care. It demonstrates the correlations between patterns of visibility and the users’ sense of control, orientation in space, teamwork, safety, quality of care, and wellbeing. Conclusions: The case study demonstrates the limitations of current telemedicine technologies that were not designed for inpatient care to account for the spatial perception of the unit and the dynamic use of the space. It presents the potential of a hybrid model that balances virtual and physical forms of visibility and suggests directions for future research and development of inpatient telemedicine.This work was supported by the Centre for Digital Built Britain (CDBB) at the University of Cambridge [RG96631 NSAG/202]. E. Oborn is part supported by the National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care West Midlands [Grant WMCLAHRC-2014-1]