Extended clinical phenotypes and treatment modalities in 32 JAGN1-deficient patients. A multicenter study by EBMT IEWP.

JAGN1 (Jagunal-homolog1) is a ER-resident transmembrane protein which is part of the early secretory pathway and granulocyte colony-stimulating factor receptor mediated signaling. Autosomal recessively inherited variants in the JAGN1 gene lead to congenital neutropenia, early-onset bacterial infections, aphthosis and skin abscesses due to aberrant differentiation and maturation of neutrophils. In addition, bone metabolism disorders and a syndromic phenotype, including facial features, short stature and neurodevelopmental delay, have been reported in affected patients.

Prevalence of spp. in Seafood from German Supermarkets and Fish Markets.

This study investigates the prevalence of spp. in seafood from supermarkets and fish markets in Berlin, Germany. A total of 306 seafood samples, including shrimp and mussels, were bought from supermarkets between March 2023 and January 2024.

Flavopiridol restores granulopoiesis in experimental models of severe congenital neutropenia.

Severe congenital neutropenia (CN) patients require life-long treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF), but some show no response. We sought to establish a therapy for CN that targets signaling pathways causing maturation arrest of granulocytic progenitors. We developed an isogenic induced pluripotent stem cell (iPSC) in vitro model of CN associated with ELANE mutations (ELANE-CN) and performed an in silico drug repurposing analysis of the transcriptomics of iPSC-generated hematopoietic stem and progenitor cells.

A New Severe Congenital Neutropenia Syndrome Associated with Autosomal Recessive COPZ1 Mutations.

We have identified a new inherited bone marrow (BM) failure syndrome with severe congenital neutropenia (CN) caused by autosomal recessive mutations in the coatomer protein complex I (COPI) subunit zeta 1 (COPZ1) gene. A stop-codon COPZ1 mutation and a missense mutation were found in three patients from two unrelated families. While two affected siblings with a stop-codon COPZ1 mutation suffered from congenital neutropenia (CN) that involves other hematological lineages, and non-hematological tissues, the patient with a missense COPZ1 mutation had isolated neutropenia.

Interleukin Profiling in Atopic Dermatitis and Chronic Nodular Prurigo.

The clinical manifestations of atopic dermatitis (AD) and chronic nodular prurigo (CNPG) include pruritus and eczema/lesions, posing significant challenges for patients. Th2 cells and ILC2, marked by cytokine production-particularly IL-4/13-are crucial therapeutic targets. Despite displaying a dose-dependent lack of pruritus induction post-injection, IL-13 acts through the IL-13Rα1 and IL-13Rα2 receptor system.

[Patient survey on the use of video consultation in the outpatient treatment of chronic pruritus].

Background: Analyses of patient evaluations and barriers to the implementation of teledermatology procedures are still rare. The aim of this study was to determine whether administrative processes have an influence on the patient evaluation of telephone and video consultations.

Methods: With the help of a patient survey, assessments of the processes and organisation surrounding the outpatient appointment were asked.

Acceptability and perceived benefits of validated pruritus assessment instruments in the dermatological office and clinic: The perspectives of patients and physicians.

Background: Several patient-reported outcome measures (PROMs) have been developed for research to assess the multiple dimensions of chronic pruritus (CP). The acceptability and perceived benefits of their use in clinical practice remain unknown.

Objectives: To assess the acceptability and perceived benefits of validated PROMs from the perspective of patients and physicians in dermatological offices and clinics.

EADV Task Force Pruritus White Paper on chronic pruritus and chronic prurigo: Current challenges and future solutions.

Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous.

Validation of a scoring algorithm for the clinician-reported outcome tool 'prurigo activity and severity (PAS)' based on clinical studies of dupilumab in adults with prurigo Nodularis.

Background: Prurigo nodularis (PN) also known as chronic prurigo, is a chronic inflammatory skin disease characterized by intensely itchy nodules/lesions which occur due to intensive scratching. PN management is, in part, based on clinician evaluations of PN lesions, which can be supported by clinician-reported outcomes (ClinRO) such as the Prurigo Activity and Severity (PAS) instrument. A 5-item version of PAS was included in recent phase-3 dupilumab PN trials (PRIME [NCT04183335]/PRIME2 [NCT04202679]).

CRISPR-Cas9n-mediated ELANE promoter editing for gene therapy of severe congenital neutropenia.

Severe congenital neutropenia (CN) is an inherited pre-leukemia bone marrow failure syndrome commonly caused by autosomal-dominant ELANE mutations (ELANE-CN). ELANE-CN patients are treated with daily injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF). However, some patients do not respond to rhG-CSF, and approximately 15% of ELANE-CN patients develop myelodysplasia or acute myeloid leukemia.

Dermatological patients with itch report more stress, stigmatization experience, anxiety and depression compared to patients without itch: Results from a European multi-centre study.

Background: Itch as the most common symptom in dermatology has been shown to be related to psychological factors such as stress, anxiety and depression. Moreover, associations were found between perceived stigmatization and itch. However, studies investigating the differences between patients with dermatoses with and without itch regarding perceived stress, stigmatization, anxiety and depression are missing.

Development and Validation of a Patient-Reported Outcome Measure to Assess Disease Control in Chronic Prurigo.

Importance: Chronic prurigo (CPG), including prurigo nodularis, is a difficult disease to treat and considerably affects patients' quality of life. Helping patients obtain control of CPG is a major treatment goal.

Objective: To develop and validate the Prurigo Control Test (PCT), a tool for assessing disease control in CPG, and to identify a cutoff value for controlled disease to aid treatment decisions.

Differential transcriptional control of hematopoiesis in congenital and cyclic neutropenia patients harboring mutations.

Mutations in the ELANE gene, encoding the neutrophil elastase (NE) protein, are responsible for most cyclic neutropenia (CyN) cases and approximately 25% of congenital neutropenia (CN) cases. In CN and in CyN, a median of 2.8% of CD34+ cells were early CD49f+ hematopoietic stem cells (eHSC) that did not express ELANE and thus escape from the unfolded protein response (UPR) caused by mutated NE.

Effect of the addition of a mental health specialist for evaluation of undiagnosed patients in centres for rare diseases (ZSE-DUO): a prospective, controlled trial with a two-phase cohort design.

Background: People with complex symptomatology but unclear diagnosis presenting to a centre for rare diseases (CRD) may present with mental (co-)morbidity. We hypothesised that combining an expert in somatic medicine with a mental health specialist working in tandem will improve the diagnostic outcome.

Methods: Patients aged 12 years and older who presented to one of the 11 participating German CRDs with an unknown diagnosis were recruited into this prospective cohort trial with a two-phase cohort design.