[Anesthesiological aspects in patients with epidermolysis bullosa]. / Anästhesiologische Aspekte bei Patienten mit Epidermolysis bullosa.

Epidermolysis bullosa causes blistering due to altered structural proteins of the dermoepidermal junction, resulting in scarring and strictures of the skin and mucous membranes. Affected individuals typically require frequent surgical interventions due to burdensome symptoms and complications of the disease. The anesthesiological management of these patients is inherently challenging. This review article summarizes the relevant features of this patient cohort and provides practical recommendations for care.

Otological complications in inversa type recessive dystrophic epidermolysis bullosa.

BACKGROUND: The rare inversa subtype of recessive dystrophic epidermolysis bullosa (RDEB-I) is characterized by predominant intertriginous skin blistering and marked mucosal involvement. Specific recessive missense mutations in the collagen VII triple helix are implicated in the disease. To date, otological complications have been reported infrequently in this patient group. METHODS: We conducted an observational, retrospective, double institution case record review of patients with RDEB-I who presented with otological complications between January 2000 and June 2020. Diagnosis was established on the basis of clinical features, family history and mutation analysis of the COL7A1 gene. RESULTS: In total, 11 (44%) of 25 patients with RDEB-I in our database (2 paediatric, 9 adult; mean age 40.9 years, range 8-72 years) experienced otological complications. Of these 11 patients, 10 (90.9%) had recurrent otitis externa, 7 (63.6%) had meatal stenosis and 7 (63.6%) had recurrent blistering of the external auditory canals. All 11 patients reported hearing difficulties, with conductive hearing loss confirmed by audiology testing in 6 (54.5%) of these. Of the 11 patients, 3 (27.3%) went on to have implantable hearing aids [2 bone-anchored hearing aids (BAHA) and 1 middle ear implant (MEI)] fitted with favourable outcome, while a fourth paediatric patient presented with a cholesteatoma that was surgically managed. DISCUSSION: We observed a higher prevalence of otological morbidity in RDEB-I than previously reported, and present the first case of cholesteatoma in epidermolysis bullosa (EB). Our data indicate that BAHA and MEI are safe and effective treatment options for hearing loss in EB. Clinicians should be vigilant in screening for ear symptoms in RDEB-I and consider early referral to an Ear, Nose and Throat specialist.

[Mucosal manifestations of epidermolysis bullosa : Clinical presentation and management]. / Schleimhautbeteiligung bei Epidermolysis bullosa : Klinik und Therapiemaßnahmen.

Mucosal lesions occur with different prevalence and severity in all subtypes of hereditary epidermolysis bullosa (EB), a group of rare genodermatoses. They are associated with increased morbidity and mortality, especially in severe junctional and dystrophic subtypes. Despite progress in clinical approaches to curative therapy, the management of these patients is still primarily symptom-oriented. Current recommendations mainly rely on expert opinion and experience from health care professionals of specialized centers, since the rarity of this disease largely limits the availability and feasibility of randomized controlled trials. Accurate preventive and supportive care measures, however, can significantly lessen symptoms, avoid/ameliorate complications, and enhance the quality of life of these patients.

Bone marrow transplantation improves the outcome of Atm-deficient mice through the migration of ATM-competent cells.

Ataxia telangiectasia (A-T) is a highly pleiotropic disorder. Patients suffer from progressive neurodegeneration, severe bronchial complications, immunodeficiency, hypersensitivity to radiotherapy and elevated risk of malignancies. Leukemia and lymphoma, along with lung failure, are the main causes of morbidity and mortality in A-T patients. At present, no effective therapy for A-T exists. One promising therapeutic approach is bone marrow transplantation (BMT) that is already used as a curative therapy for other genomic instability syndromes. We used an established clinically relevant non-myeloablative host-conditioning regimen and transplanted green fluorescent protein (GFP)-expressing ataxia telangiectasia mutated (ATM)-competent bone marrow-derived cells (BMDCs) into Atm-deficient mice. GFP expression allowed tracking of the potential migration of the cells into the tissues of recipient animals. Donor BMDCs migrated into the bone marrow, blood, thymus, spleen and lung tissue of Atm-deficient mice showing an ATM-competent phenotype. BMT inhibited thymic lymphomas, normalized T-lymphocyte populations, improved weight gain and rearing activity of Atm-deficient mice. In contrast, no GFP(+) cells were found in the cerebellum or cerebrum, and we detected decreased size index in MRI imaging of the cerebellum in 8-month-old transplanted Atm-deficient mice in comparison to wild-type mice. The repopulation with ATM-competent BMDCs is associated with a prolonged lifespan and significantly improved the phenotype of Atm-deficient mice.

The TSH receptor is linked with AP1 and NFkappaB signaling in COS7 cells.

In addition to it's classic coupling to Gs and Gq the TSHR was shown to also couple to further members of four G-protein families in membranes: G(s), G(q/11), G(i/0) and G(12/13). Moreover, GPCRs are able to stimulate mitogenic signaling pathways by switching the receptor coupling to different G-proteins or by interacting with scaffold proteins like beta-arrestins. These findings lead to the assumption of additional mitogenic TSHR stimulated signaling pathways. Therefore, we systematically investigated whether the TSH receptor is able to stimulate signaling pathways apart from the known cAMP and IP pathways. We used a luciferase reporter gene assay containing response elements covering a variety of signal transduction pathways. After TSH-stimulation the TSHR showed a significantly increased CRE-, AP1- or NFkappaB-mediated luciferase accumulation in COS7 cells. No effect on luciferase accumulation was found for the other reporter gene vectors. These findings lead to the hypothesis of a possible relevance of AP1 and NFkappaB for TSHR-dependent signaling pathways in COS cells which act in addition to the known cAMP and IP pathways.