A 79-year-old female presented to the emergency department for sudden-onset ocular pain, edema, and erythema around her left eye. She also had a left-sided migraine and frontal fullness for 2 weeks. She had attentive care for the diagnosis of orbital cellulitis and prompt recognition of necrotizing fasciitis. Wound cultures were positive for over 5 strains of bacteria in addition to Aspergillus. In a combined effort by our institution\'s Ophthalmology and Otolaryngology departments, the patient was successfully treated with debridement, porcine bladder matrix, antibiotics, and antifungals. The authors describe the first reported case of eyelid and periorbital necrotizing fasciitis, caused by mixed flora and Aspergillus fumigatus, that showed promising wound healing with the outlined treatment paradigm.

Follicular thyroid carcinoma (FTC) is recognized by its ability to invade the tumor capsule and blood vessels, although the exact molecular signals orchestrating this phenotype remain elusive. In this study, the spatial transcriptional landscape of an FTC is detailed with comparisons between the invasive front and histologically indolent central core tumor areas. The Visium spatial gene expression platform allowed us to interrogate and visualize the whole transcriptome in 2D across formalin-fixated paraffin-embedded (FFPE) tissue sections. Four different 6 × 6 mm areas of an FTC were scrutinized, including regions with capsular and vascular invasion, capsule-near area without invasion, and a central core area of the tumor. Following successful capturing and sequencing, several expressional clusters were identified with regional variation. Most notably, invasive tumor cell clusters were significantly over-expressing genes associated with pathways interacting with the extracellular matrix (ECM) remodeling and epithelial-to-mesenchymal transition (EMT). Subsets of these genes (POSTN and DPYSL3) were additionally validated using immunohistochemistry in an independent cohort of follicular thyroid tumors showing a clear gradient pattern from the core to the periphery of the tumor. Moreover, the reconstruction of the evolutionary tree identified the invasive clones as late events in follicular thyroid tumorigenesis. To our knowledge, this is one of the first 2D global transcriptional mappings of FTC using this platform to date. Invasive FTC clones develop in a stepwise fashion and display significant dysregulation of genes associated with the ECM and EMT - thus highlighting important molecular crosstalk for further investigations.

UNASSIGNED: The quest for an ideal wound dressing has been a longstanding challenge due to the complex nature of wound healing, including stages of haemostasis, inflammation, maturation and remodelling, with overlapping timelines. This makes it difficult to find a single dressing that optimally supports all phases of wound healing. In addition, the ideal wound dressing should possess antibacterial properties and be capable of effectively debriding and lysing necrotic tissue. Copper is an essential trace element that participates in many of the key physiological wound healing processes.
UNASSIGNED: Copper stimulates secretion of various cytokines and growth factors, thus promoting angiogenesis, granulation tissue formation, extracellular matrix proteins secretion and re-epithelialisation. Harnessing this knowledge, we have used copper oxide-impregnated wound dressings in numerous cases and observed their benefits throughout the entire wound healing process.
UNASSIGNED: This led us to postulate the \'continuum of care\' hypothesis of copper dressings. In this study we describe four cases of hard-to-heal wounds of various aetiologies, in which we applied copper dressings consistently across all stages of wound healing, with rapid uneventful healing.
UNASSIGNED: We believe we have successfully implemented the continuum of care principle.

UNASSIGNED: Volumetric soft tissue loss is an urgent surgical issue and can frequently lead to suboptimal outcomes for patients due to significant soft tissue loss, compromised vital structures, and contamination. Ovine forestomach matrix (OFM) has demonstrated clinical success in the surgical management of soft tissue defects, especially in contaminated fields, and provides an effective option for immediate coverage of exposed vital structures before definitive closure.
UNASSIGNED: This retrospective pilot case series (n = 13 defects) evaluated the clinical effectiveness of OFM (graft and/or particulate formats) in the surgical management of contaminated volumetric soft tissue defects. Patients presented with significant soft tissue loss, often with exposed viscera, tendon, bone, or muscle, and were treated with OFM as part of their inpatient surgical management. All patients had at least 1 significant comorbidity with the potential to complicate their healing trajectory. The primary study endpoint was time to 100% granulation tissue coverage (days), and the secondary endpoint was any device-related postoperative complications.
UNASSIGNED: A total of 13 volumetric soft tissue defects were evaluated in 10 patients who underwent surgical reconstruction. Mean defect age was 3.5 ± 5.6 weeks, and mean area was 217.3 ± 77.9 cm2. Most defects had exposed structures (85%), and all defects were Centers for Disease Control and Prevention grade 2 or higher. Mean time to 100% granulation tissue formation was 23.4 ± 9.2 days, with a median product application of 1.0. Staged reconstruction was used in 7 of 13 defects, with the remainder (6 of 13) left to heal via secondary intention using standard wound care protocols. There were no major postoperative infections or adverse events (mean follow-up, 7.4 ± 2.4 weeks.).
UNASSIGNED: This retrospective pilot case series builds on a growing body of evidence that OFM can be utilized to facilitate the formation of functional, well-vascularized soft tissue in large contaminated volumetric soft tissue defects.

Biofilm formation protects bacteria from antibiotic treatment and host immune responses, making biofilm infections difficult to treat. Within biofilms, bacterial cells are entangled in a self-produced extracellular matrix that typically includes exopolysaccharides. Molecular-level descriptions of biofilm matrix components, especially exopolysaccharides, have been challenging to attain due to their complex nature and lack of solubility and crystallinity. Solid-state nuclear magnetic resonance (NMR) has emerged as a key tool to determine the structure of biofilm matrix exopolysaccharides without degradative sample preparation. In this review, we discuss challenges of studying biofilm matrix exopolysaccharides and opportunities to develop solid-state NMR approaches to study these generally intractable materials. We specifically highlight investigations of the exopolysaccharide called Pel made by the opportunistic pathogen, Pseudomonas aeruginosa. We provide a roadmap for determining exopolysaccharide structure and discuss future opportunities to study such systems using solid-state NMR. The strategies discussed for elucidating biofilm exopolysaccharide structure should be broadly applicable to studying the structures of other glycans.

Chronic ulcers pose a public health challenge. Thus, it is imperative to be aware of and assess new management strategies that contribute to patient quality of life and optimize health resources. This study evaluated the efficacy of a new protocol for chronic wound management that includes porcine intestine ECM.
Twenty-one patients with chronic wounds of different etiologies were included in this study. A new healing protocol that incorporates the use of porcine ECM was initiated for a maximum period of 12 weeks. Follow-up included a weekly visit to photograph the ulcers and record their size.
Wounds ranged in size from 0.5 cm2 to 10 cm2 at the outset of the study. Two of the 21 patients who started the protocol withdrew, 1 for nonadherence to the protocol and 1 for health complications unrelated to the study. Most lesions occurred in the lower limbs. All patients who completed the treatment protocol achieved wound regeneration and total wound closure within an average of 4.5 weeks. The average percentage closure rate was 100% at 8 weeks, with no AEs.
The findings of this study demonstrate the efficacy of an evidence-based wound management protocol in achieving safe, complete tissue regeneration in a short period of time.

UNASSIGNED: Dehiscence and infection of hard-to-heal surgical wounds results in an increased risk of complications and mortality. A hard-to-heal surgical wound will present decreased levels of growth factors along with increased levels of debris and matrix metalloproteinases, resulting in the destruction of the extracellular matrix (ECM). ActiGraft (RedDress Ltd., Israel) is an autologous whole blood clot treatment, created at a point of care, to promote wound healing. We hereby present the efficacy of ActiGraft in a case series of hard-to-heal surgical wounds.
UNASSIGNED: A registry study of patients with surgical wounds was conducted in private clinics and hospitals across the US and Israel (NCT04699305). Autologous whole blood clot was created at point of care using the patient\'s own blood.
UNASSIGNED: A total of 14 patients took part in the study. Autologous whole blood clot treatment resulted in a mean percent wound area reduction of 72.33% at four weeks, with 33.33% of wounds achieving complete closure by week 4. At week 12, 78.54% of the wounds achieved complete closure.
UNASSIGNED: Surgical wounds in patients with comorbidities may fail to initiate the natural wound healing mechanism which in turn may cause deterioration of the wound into a hard-to-heal stage. In this case series, autologous whole blood clot treatment was able to restore wound healing, avoiding the risk of infection and amputation of an affected limb. The properties of autologous whole blood clot as an ECM reduce the risk of infection, causing the wound to progress from the inflammatory phase to the proliferative phase. Autologous whole blood clot treatment in hard-to-heal surgical wounds was found to be an effective approach, reducing the risk of infection and promoting cell granulation, resulting in wound closure.

Although cancer-associated fibroblasts (CAFs) have gained increased attention for supporting cancer progression, current CAF-targeted therapeutic options are limited and failing in clinical trials. As the largest component of the tumor microenvironment (TME), CAFs alter the biochemical and physical structure of the TME, modulating cancer progression. Here, we review the role of CAFs in altering drug response, modifying the TME mechanics and the current models for studying CAFs. To provide new perspectives, we highlight key considerations of CAF activity and discuss emerging technologies that can better address CAFs; and therefore, increase the likelihood of therapeutic efficacy. We argue that CAFs are crucial components of the cancer drug discovery pipeline and incorporating these cells will improve drug discovery success rates.
Recent advances in cancer research have improved our understanding of disease progression; however, the number of drugs failing in clinical trials remains high and therefore, present a critical challenge for cancer drug discovery. Although the interactions of the tissue surrounding the tumor, the tumor microenvironment, are now considered key targets for new interventions in cancer, the role of microenvironment is largely absent in drug discovery pipelines. Here we explore the role of the most prominent cell type in the tumor microenvironment, cancer-associated fibroblasts (CAFs), in altering cancer therapy response and ultimately patient outcome. To provide new perspectives for future studies, we draw attention to key complications of CAF biology and highlight emerging technologies that could be used to address this. We believe including CAFs in drug discovery, whether for targeting cancer cells or the microenvironment, will allow for a better understanding of therapeutic efficacy and ultimately improve clinical outcome.

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The genomic region surrounding the Tenascin-XB gene (TNXB) is a complex and duplicated region, with several pseudogenes that predispose to high rates of homologous recombination. Classical-like Ehlers-Danlos syndrome (clEDS) is the result of tenascin-X deficiency due to biallelic loss of function variants in the TNXB gene. Here we present a patient with clEDS and spontaneous pneumothorax, a feature not previously reported to be associated with this condition. Two inherited pathogenic/likely pathogenic variants were identified; a previously reported deletion resulting in a TNXA/TNXB chimeric gene and a novel frameshift variant. The Tenascin-XB gene is well described in the literature to be associated with collagen metabolism, stabilization of the fibrillar-collagen matrix and is expressed abundantly in the extracellular matrix. We propose that tenascin-X deficiency is directly related to pneumothorax predisposition. This case expands the phenotypic spectrum of clEDS and highlights the challenges with molecular analysis and diagnosis.