Single-cell RNA sequencing defines disease-specific differences between chronic nodular prurigo and atopic dermatitis.

BACKGROUND: Chronic nodular prurigo (CNPG) is an inflammatory skin disease that is maintained by a chronic itch-scratch cycle likely rooted in neuroimmunological dysregulation. This condition may be associated with atopy in some patients, and there are now promising therapeutic results from blocking type 2 cytokines such as IL-4, IL-13, and IL-31. OBJECTIVES: This study aimed to improve the understanding of pathomechanisms underlying CNPG as well as molecular relationships between CNPG and atopic dermatitis (AD). METHODS: We profiled skin lesions from patients with CNPG in comparison with AD and healthy control individuals using single-cell RNA sequencing combined with T-cell receptor sequencing. RESULTS: We found type 2 immune skewing in both CNPG and AD, as evidenced by CD4+ helper T cells expressing IL13. However, only AD harbored an additional, oligoclonally expanded CD8A+IL9R+IL13+ cytotoxic T-cell population, and immune activation pathways were highly upregulated in AD, but less so in CNPG. Conversely, CNPG showed signatures of extracellular matrix organization, collagen synthesis, and fibrosis, including a unique population of CXCL14-IL24+ secretory papillary fibroblasts. Besides known itch mediators such as IL31 and oncostatin M, we also detected increased levels of neuromedin B in fibroblasts of CNPG lesions compared with AD and HC, with neuromedin B receptors detectable on some nerve endings. CONCLUSIONS: These data show that CNPG does not harbor the strong disease-specific immune activation pathways that are typically found in AD but is rather characterized by upregulated stromal remodeling mechanisms that might have a direct impact on itch fibers.

Retroauricular lymph node flap: An anatomic and surgical feasibility study.

BACKGROUND: The study investigated the anatomy of the retroauricular lymph node (LN) flap and evaluate its surgical feasibility as a new donor site for a free LN flap in lymphedema surgery. METHODS: Twelve adult cadavers were examined. The course and perfusion of the anterior auricular artery (AAA) and the location and sizes of the retroauricular LNs were studied. RESULTS: The AAA was available in 87% and absent in 13% specimens. The AAA's origin had a mean vertical distance of 12.2 ± 6.9 mm and a mean horizontal distance of 19.1 ± 4.2 mm from the superior attachment of the ear. The mean diameter of the AAA was 0.8 ± 0.2 mm. The mean number of LN per region was 7.7 ± 2.3, with an average LN size of 4.1 ± 1.9 × 3.2 ± 1.7 mm. The LN were categorized into anterior (G1) and posterior (G2) groups, with a total of 59 and 10 LN, respectively. In a cluster analysis, three LN clusters could be detected across the anterior group (G1). CONCLUSIONS: The retroauricular LN flap is a delicate but feasible flap with reliable anatomy, containing a mean of 7.7 LNs.

[Peripheral nerve reconstruction - diagnostics as a basis for decision-making: report of the Consensus Workshop at the 35th Meeting of the DAM]. / Periphere Nervenrekonstruktion ­ Diagnostik als Grundlage der Entscheidungsfindung ­ Bericht des Consensus-Workshops im Rahmen der 35. Jahrestagung der Deutschsprachigen Gemeinschaft für Mikrochirurgie der peripheren Nerven und Gefäße (DAM).

In the early stage of nerve lesions, the clinical differentiation between neurapraxia, axonotmesis and neurotmesis often presents a big challenge. Especially in the early stage, however, it is crucial to correctly classify the type of damage because this is what essentially determines the therapeutic concept, in particular the surgical approach and, therefore, the prognosis. A precise diagnosis not only requires detailed clinical assessment and medical history taking, but also the use of additional electrophysiological (functional) and/or imaging examinations. Electrophysiological diagnostic tests may provide information ion localization, severity, course, type of damage and incipient or past reinnervation. Preoperative functional diagnostic measures should include neurography, needle electromyography (EMG) and, if needed, evoked potentials (EP), while imaging procedures should include neural sonography and magnetic resonance imaging (MRI). As a complimentary procedure, EMG may also be performed during surgery.

Anatomical Study of a Chimeric Fascio-Osteomyocutaneous Fibula Flap for Free Microvascular Tissue Transfer.

BACKGROUND: Functional restoration in reconstructive surgery can require complex and adaptable approaches. In this anatomical study, the combined angiosome of the septofasciomyocutaneous vessels originating from the fibular artery was defined as basis for a chimeric flap of the lateral lower leg. METHODS: Methylene blue injection into the fibular artery was performed in 10 legs of fresh cadavers for visualization of the angiosome on the skin, fibula, and adjacent muscles as the lateral hemisoleus (HS) muscle. With regards to clinical specifications a maximum-size flap containing cutaneous, osseous, and muscular elements was raised. During dissection, the distribution pattern, number and size of stained septofasciomyocutaneous vessels at the lateral border of the proximal, middle, and distal thirds of the fibula length, as well as the flap dimensions were evaluated. RESULTS: In all specimens, vessels originating from the fibular artery and supplying the resected fibular bone, the fasciocutaneous flap and dorsally located muscles were found. The mean number of vessels to the skin was 4.2 per leg with a mean diameter of 1.1 ± 0.5 mm (range: 0.4-2.5 mm) and to the HS muscle 3.4 vessels with a mean diameter of 1.2 ± 0.7 mm (range: 0.3-3.0 mm). A total of 88.4% vessels occurred in the proximal and middle thirds of the legs. The resected fibula graft had a mean length of 23.8 ± 3.9 cm (range: 19.9-31.0 cm) and the skin paddle had a mean size of 23.8 ± 3.9 cm (range: 19.9-31.0 cm) × 7.0 cm. The flexor hallucis longus (FHL) muscle had a mean volume of 37.2 ± 15.8 cm3 (range: 18-58 cm3) and the lateral HS muscle 77.1 ± 23.3 cm3 (range: 48-105 cm3). CONCLUSION: Our results and anatomical descriptions indicate that chimeric fibula flaps can meet the specific reconstructional requirements of complex and large sized defects representing a promising basis for further studies.

Incidence of risk factors for bloodstream infections in patients with major burns receiving intensive care: A retrospective single-center cohort study.

OBJECTIVES: The objective was primarily to identify risk factors for bloodstream infections (BSI) caused by different pathogens. METHODS: A retrospective single-center cohort study was performed on 472 burn patients with an abbreviated burn severity index (ABSI)≥3, a total burn surface area (TBSA)≥10%, and an ICU stay of at least 24h. Risk factors for different BSI pathogens were analyzed by competing risks regression model of Fine and Gray. RESULTS: A total of 114 burn patients developed 171 episodes of BSIs caused by gram-negative bacteria (n=78;46%), gram-positive bacteria (n=69;40%), and fungi (n=24;14%) median after 14days (range, 1-164), 16days (range, 1-170), and 16days (range, 0-89), respectively. A total of 24/114 patients (21%) had fatal outcomes. Isolation of the most common bloodstream isolates Enterococcus sp. (n=26), followed by Candida sp. and Pseudomonas sp. (n=22 for both) was significantly associated with increased TBSA (p≤0.006) and ABSI (p<0.0001) and need for fasciotomy (p<0.01). The death risk of patients with MDR gram-negative bacteremia was significantly increased by a hazard ratio of 12.6 (95% CI:4.8-32.8; p<0.0001). CONCLUSIONS: A greater TBSA and ABSI were associated with a significantly higher incidence of BSIs caused by Pseudomonas sp., Enterococcus sp. and Candida sp.