Wound Center Research Articles

Prevalence and incidence of chronic wounds in Austria - a population-based real-world data analysis

Abstract Background Chronic wounds are associated with pain, odor, loss of mobility, an increased risk for infection and sepsis and a reduced quality of life. Treatment costs are rising due to the longevity of the population and increasing number of diabetes cases. For service planning in healthcare, it is thus necessary to describe patient characteristics and estimate the prevalence and incidence of chronic wounds. Currently, no data exists on this subject broken down by age group, gender, and province in Austria. Methods A retrospective analysis of real-world data was conducted using two merged datasets from an outpatient wound centre and the Austrian Health Insurance Fund. The study population consisted of people who resided in Austria and were covered by statutory health insurance from 2018 to 2022. We performed a descriptive, socio-demographic analysis of the data of patients, followed by a set of cluster analyses using the unsupervised K-means algorithm. From these clusters, we derived subgroup characteristics and patient trajectories and calculated prevalence and incidence rates for chronic wounds according to diagnoses, different age groups, gender, and different regions. Results Gender was almost evenly distributed in the wound centre’s data set (n = 4963; 49.6% female). The age distribution revealed the age group from 71-80 years being the largest group. In general, more women than men are affected by chronic wounds from the age of 81 onwards. 31% of chronic wound patients had diabetes as an underlying condition. More men were affected by peripheral arterial occlusive disease and diabetic foot syndrome and, conversely, more women by chronic venous insufficiency. These are preliminary results of the analyses. Conclusions Chronic wound patients were characterised by older age and multi-morbidity. Interestingly, gender differences appeared in the occurrence of comorbidities. Key messages • This study makes a crucial contribution in making routine data usable for the epidemiological study of chronic wounds, a cluster of diseases of complex aetiology. • It thus contributes to filling a knowledge gap. The prevalence estimate serves as a basis of knowledge for health care planning and a basis for the health economic assessment of the problem.

A Comparative Analysis of Patient-Reported Outcomes Following Free Tissue Transfer, Partial Foot Amputation, and Below-Knee Amputation in High-Risk Limb Salvage Patients.

The surgical decision for limb-salvage with free tissue transfer (FTT), partial foot amputation (PFA), or below-knee amputation (BKA) for complex lower extremity (LE) wounds hinges on several factors, including patient choice and baseline function. However, patient-reported outcome measures (PROMs) on LE function, pain, and QoL for chronic LE wound interventions are limited. Thus, the study aim was to compare PROMs in patients who underwent FTT, PFA, or BKA for chronic LE wounds. PROMs were collected via QR code for all adult chronic LE wound patients who presented to a tertiary wound center between June 2022 and June 2023. A cross-sectional analysis of patients who underwent FTT, PFA, or BKA was conducted. The 12-Item Short Survey (SF-12), PROM Information System Pain Intensity (PROMIS-3a), and Lower Extremity Functional Scale (LEFS) were completed at 1, 3, and 6 months and 1, 3, and 5 years postoperatively. Patient demographics, comorbidities, preoperative characteristics, and amputation details were collected. Of 200 survey sets, 71 (35.5%) underwent FTT, 51 (25.5%) underwent PFA, and 78 (39.0%) underwent BKA. Median postoperative time points of survey completion between FTT (6.2 months, IQR: 23.1), PFA (6.8 months, IQR: 15.5), and BKA (11.1 months, IQR: 21.3) patients were comparable (P = 0.8672). Most patients were male (n = 92, 76.0%) with an average age and body mass index (BMI) of 61.8 ± 12.6 years and 30.3 ± 7.0 kg/m2, respectively. Comorbidities for FTT, PFA, and BKA patients included diabetes mellitus (DM; 60.6% vs 84.2% vs 69.2%; P = 0.165), peripheral vascular disease (PVD; 48.5% vs 47.4% vs 42.3%; P = 0.790), and chronic kidney disease (CKD; 12.1% vs 42.1% vs 30.8%; P = 0.084). No significant differences were observed between FTT, PFA, and BKA patients in mean overall PROMIS-3a T-scores (49.6 ± 14.8 vs 54.2 ± 11.8 vs 49.6 ± 13.7; P = 0.098), LEFS scores (37.5 ± 18.0 vs 34.6 ± 18.3 vs 38.5 ± 19.4; P = 0.457), or SF-12 scores (29.6 ± 4.1 vs 29.5 ± 2.9 vs 29.0 ± 4.0; P = 0.298). Patients receiving FTT, PFA, or BKA for chronic LE wounds achieve comparable levels of LE function, pain, and QoL postoperatively. Patient-centered functionally based surgical management for chronic LE wounds using interdisciplinary care, preoperative medical optimization, and proper patient selection optimizes postoperative PROMs.

Dynamic optical coherence tomography for imaging acute wound healing.

The aim of this study was to investigate acute wound healing with dynamic optical coherence tomography (D-OCT). From 22 patients with 23 split skin graft donor sites, vessels at four wound edges, the wound bed, and adjacent and unaffected skin of the contralateral leg were measured by D-OCT at six time points from surgery to 4 weeks of healing. Changes in vessel orientation, density, diameter, morphology and pattern in horizontal, vertical and 3D images were analysed for wound healing and re-epithelialization. At 300 μm depth, there were significant differences of blobs and serpiginous vessels between normal and wounded skin. The wound had significantly more vertically oriented vessels, a higher degree of branching, vessel density and diameter compared with healthy skin. 3D images showed increased angiogenesis from healthy skin towards the wound centre, significantly higher vessel density at the wound than at normal skin and the highest at the interface. During wound healing blobs, coils and serpiginous vessels occurred significantly more frequently in lesional than healthy skin. Vessel density was greatest at the beginning, decreased and then increased by 4 weeks post-surgery. D-OCT helps to evaluate acute wound healing by visualizing and quantifying blood vessel growth in addition to re-epithelialization.

Characteristics of chronic ulcer patients by gender and ulcer aetiology from a multidisciplinary wound centre.

Chronic ulcer patients form a heterogenous group of patients with various medical backgrounds. Cost-effective targeted treatment necessitates more knowledge about specific features related to different subgroups of ulcer patients. Hence, this study aimed to characterize ulcer patients according to gender and ulcer aetiology. A total of 946 consecutively recorded chronic ulcer patients in the Tampere Wound Registry (TWR) were included and data were gathered from the TWR and patient medical records. Comparisons were made between males and females and patients with venous-, arterial or mixed-, diabetic foot-, pressure- and atypical ulcers. Male patients were found to have diabetes, hypercholesterolemia and obesity significantly more often than females (59.2% vs. 39.6%; p < 0.001, 46.5% vs. 33.3%; p = 0.001, 42.7% vs. 35.9%; p = 0.017 respectively), whereas autoimmune diseases were more common among females (30.6% vs. 15.6%; p < 0.001). Recurrence of ulcers was most common among patients with venous ulcers (p < 0.001) and multimorbidity among those with diabetic foot ulcers (p < 0.001). To conclude, males with chronic ulcers would benefit particularly from lifestyle advice, multidisciplinary treatment should be targeted specifically at those with diabetic and arterial or mixed ulcers and preventive measures at those with venous ulcers.

Blistering Disorders of the Foot.

Multiple pathophysiologic and biomolecular processes lead to bullae, including disruption of adhesion molecules, accumulation of cell injury, and traumatic injury. Blistering disorders of the foot can cause symptoms such as pruritus, pain, and drainage and significantly impact quality of life. Microbiologic and histopathologic examination of tissue specimens should be considered for concerns regarding atypical etiology.This retrospective case series describes patients seen in a community hospital outpatient wound center in southeastern Wisconsin between January 2021 and June 2023 for atypical blistering disorders of the foot. The cases herein describe the history, clinical presentation, and treatment of three atypical blistering disorders of the foot. An 86-year-old man presented complaining of intensely pruritic blistering lesions to both feet. Histopathologic findings indicated eosinophilic infiltrate, and the patient was treated for an eosinophilic drug reaction. A 65-year-old man presented complaining of multiple painful blisters to the plantar aspect of both feet. Histopathologic examination of unroofed blister indicated bullous tinea. Finally, a 44-year-old man with long-standing type 1 diabetes presented complaining of a several-week history of a single blister to his anterior right foot of unknown etiology. The patient was diagnosed with bullosis diabeticorum.Blistering disorders of the foot are diagnostic challenges; diagnostic clarity is assisted by thorough history, clinical presentation, treatment response, microbial analysis, and histopathologic findings.

Tryptophan intrinsic fluorescence from wound healing correlates with re-epithelialization in a rabbit model.

Wound healing monitoring and timely decision-making are critical for wound classification. Tryptophan (Tr) intrinsic fluorescence, detected at 295/340nm, provides a noninvasive approach for wound assessment. Our previous work demonstrated that this autofluorescence is associated with keratinocytes in a highly proliferative state in vitro. We investigated the correlation between Tr fluorescence and key wound healing parameters, including re-epithelialization, fibrosis, neovascularization, and acute and chronic inflammation, using a rabbit model. Seven rabbits underwent wound healing assessment over a 15-day period. We employed histological analysis from central and marginal biopsies, and UV fluorescence imaging captured by a monochromatic near-UV sensitive camera equipped with a passband optical filter (340nm/12nm). Excitation was achieved using a 295nm LEDs ring lamp. Normalized fluorescence values were correlated with histological measurements using Pearson correlation. The UV fluorescence strongly exhibited a strong correlation with re-epithelization (r=0.8) at the wound edge, with peak intensity observed between the sixth and ninth days. Notably, wound-healing dynamics differed between the wound center and edge, primarily attributed to variations in re-epithelialization, neovascularization, and chronic inflammation. Our findings highlight the presence of autofluorescence at 295/340nm during wound healing, demonstrating a robust association with re-epithelialization. This excitation/emission signal holds promise as a valuable noninvasive strategy for monitoring wound closure, re-epithelialization, and other biological processes where Tr plays a pivotal role.

The role of split-thickness skin grafting in the treatment of vasculitic and pyoderma gangrenosum ulcers in a multidisciplinary wound centre.

Vasculitic and pyoderma gangrenosum ulcers are traditionally treated with immunosuppressants, and the role of surgery in the treatment of these atypical ulcers remains unclear. This study aimed to investigate the need for surgical intervention as well as the outcome and safety of skin grafting in the treatment of 46 patients with vasculitic ulcers and 34 with pyoderma gangrenosum ulcers using data recorded in the validated Wound Registry. Of the 80 patients with atypical ulcers, 14% (n = 11) were treated surgically; these patients were older (p = 0.039), had lower mobility status (p = 0.002), and more often pulmonary diseases, rheumatoid arthritis, and previous arterial procedures (p = 0.007; p = 0.031; p = 0.031, respectively) than those treated conservatively. Of 181 ulcers, 15% (n = 27) were surgically treated, 78% once and 22% multiple times. During follow-up, 92.3% of both surgically and conservatively treated ulcers with available data healed. Of the surgically treated ulcers, median healing time after first surgical procedure was 96 days, and post-surgical complications were considered mild or unrelated to surgery. Our results suggest that if surgery is indicated, skin grafting is a safe and efficient treatment method provided that multidisciplinary approach is applied.

Electric fields reverse the differentiation of keratinocyte monolayer by down-regulating E-cadherin through PI3K/AKT/Snail pathway

Re-epithelialization is an important step in skin wound healing, referring to the migration, proliferation, and differentiation of keratinocytes around the wound. During this process, the edges of the wound begin to form new epithelial cells, which migrate from the periphery of the wound towards the center, gradually covering the entire wound area. These newly formed epithelial cells proliferate and differentiate, ultimately forming a protective layer over the exposed dermal surface. Wound endogenous electric fields (EFs) are known as the dominant factor to facilitate the epidermal migration to wound center. However, the precise mechanisms by which EFs promote epidermal migration remains elusive. Here, we found that in a model of cultured keratinocyte monolayer in vitro, EFs application reversed the differentiation of cells, as indicated by the reduction of the early differentiation markers K1 and K10. Genetic manipulation confirmed that EFs reversed keratinocyte differentiation through down-regulating the E-cadherin-mediated adhesion. By RNA-sequencing analysis, we screened out Snail as the transcription suppressor of E-cadherin. Snail knockdown abolished the down-regulation of E-cadherin and the reversal of differentiation induced by EFs. KEGG analysis identified PI3K/AKT signaling for Snail induction under EFs. Inhibition of PI3K by LY294002 diminished the EFs-induced AKT activation and Snail augmentation, largely restoring the level of E-cadherin reduced by EFs. Finally, in model of full-thickness skin wounds in pigs, we found that weakening of the wound endogenous EFs by the direction-reversed exogenous EFs resulted in an up-regulation of E-cadherin and earlier differentiation in newly formed epidermis in vivo. Our research suggests that electric fields (EFs) decrease E-cadherin expression by suppressing the PI3K/AKT/Snail pathway, thereby reversing the differentiation of keratinocytes. This discovery provides us with new insights into the role of electric fields in wound healing. EFs intervene in intracellular signaling pathways, inhibiting the expression of E-cadherin, which results in a lower differentiation state of keratinocytes. In this state, keratinocytes exhibit increased migratory capacity, facilitating the migration of epidermal cells and wound reepithelialization.

Teleconsulting in wound care: Connecting the primary care to the wound specialist reduces unnecessary referrals.

In the Netherlands the primary care (General Practitioner or homecare nurse) encounter a variety of wounds ranging from traumatic to diabetic foot ulcers. According to a recent study 82.4% of the patients with a wound can be treated in a primary setting with the GP as medical supervisor. The remaining 17.6% of patients need more extensive care including advice by a specialised doctor, diagnosis and treatment. Prompt analyses and treatment of underlying causes by specialised doctors in a multidisciplinary setting is necessary for treating patients with complicated wound. This article describes the impact of Electronic Health Consultation on all wounds treated in the primary care. And describes the effect on the duration until referral to the hospital and the influence on the amount of unnecessary referrals to the hospital. All data was collected prospectively from June 2020 until October 2021. The study involved a process where primary care could seek advice from a Wound Physician at the Alrijne Wound Centre through a specialised Electronic Health Consultation. A total of 118 patients were analysed. 41/118 (34.7%) patients required a physical consultation with analysis and treatment in the hospital, after teleconsultation. The remaining 77/118 (65.3%) could be treated in primary care after Electronic Health Consultation. The mean duration of wound existence until Electronic Health Consultation was 39.3 days (range 5-271, SD: 38.5). 3/41 (7.3%) of the referrals were unnecessary. Electronic Health Consultation serves as a valuable and efficient tool for enhancing wound care, ultimately contributing to improved patient management and resource allocation within the healthcare system. This article describes the impact of Electronic Health Consultation on all wounds treated in the primary care and the influence on the duration until referral to the hospital and the influence on the amount of unnecessary referrals to the hospital.

Development of a Wound Epithelialization Healing Model: Reducing the Impact of Contraction Healing on the Wound Surface.

Animal experiments are important in trauma-related studies because they simulate in vivo effects. Rodents are a good choice for preparing trauma models; however, contractile healing in rodents results in a healing pattern that differs considerably from that in humans. Therefore, this study developed a new rodent model that avoids contractile healing of the skin around the wound using an anticontraction ring, and the skin in the wound's center remains intact and acts as a source for epithelialized diffusion healing. Cell proliferation, migration, revascularization, and collagen secretion did not differ between the novel and conventional full-skin defect trauma models. However, the healing rate at various stages significantly differed between the 2 groups owing to differences in the healing patterns. And without effective treatment, the experimental group cannot heal. The stabilities of the novel and conventional methods were good regardless of operator or batch. In summary, this new animal trauma model provides a stable experimental environment similar to that in humans, which may promote trauma-related research.

Identification of vanA gene on Vancomycin-Resistant Staphylococcus aureus from Diabetic Ulcer Isolate at Lampung Province

Staphylococcus aureus is a type of bacteria that causes an increasing number of infections in hospitals, particularly in diabetic ulcers. Over the last few decades, there has been an alarming increase in the prevalence of pathogen strains of Staphylococcus aureus resistant to antibiotics such as Vancomycin. This study aimed to identify the presence of the vanA gene, which is responsible for the mode of Vancomycin resistance in Staphylococcus aureus Lampung isolate. Ulcer swab was collected from 32 patients with ulcer complications from surgical Installation, Internal Medicine, Home Diabetes Wound Clinic and Diabetes Wound Center in Bandar Lampung. Among the total ulcer swab, 12 samples of S. aureus were identified and subjected to the Minimum Inhibitory Concentration test to identify Vancomycin Resistant Staphylococcus aureus and evaluated the vanA gene by Polymerase Chain Reaction. To detect the presence of the vanA gene, a Polymerase Chain Reaction was performed on Staphylococcus aureus, Vancomycin-Resistant Staphylococcus aureus, and Vancomycin-intermediate Staphylococcus aureus using a specific primer arrangement. There were two samples of Vancomycin- Resistant Staphylococcus aureus and one sample of Vancomycin-intermediate Staphylococcus aureus from the Minimum Inhibitory Concentration test but only one sample tested positive for the vanA gene on Polymerase Chain Reaction. There is Staphylococcus aureus resistance to Vancomycin in Lampung isolate and the vanA gene was detected in some resistant isolates. The arrangement of the vanA gene in the Lampung isolate is different from that of the vanA gene in other places isolates.

Hierarchically Assembled Nanofiber Scaffolds with Dual Growth Factor Gradients Promote Skin Wound Healing Through Rapid Cell Recruitment.

To address current challenges in effectively treating large skin defects caused by trauma in clinical medicine, the fabrication, and evaluation of a novel radially aligned nanofiber scaffold (RAS) with dual growth factor gradients is presented. These aligned nanofibers and the scaffold's spatial design provide many all-around "highways" for cell migration from the edge of the wound to the center area. Besides, the chemotaxis induced by two growth factor gradients further promotes cell migration. Incorporating epidermal growth factor (EGF) aids in the proliferation and differentiation of basal layer cells in the epidermis, augmenting the scaffold's ability to promote epidermal regeneration. Concurrently, the scaffold-bound vascular endothelial growth factor (VEGF) recruits vascular endothelial cells at the wound's center, resulting in angiogenesis and improving blood supply and nutrient delivery, which is critical for granulation tissue regeneration. The RAS+EGF+VEGF group demonstrates superior performance in wound immune regulation, wound closure, hair follicle regeneration, and ECM deposition and remodeling compared to other groups. This study highlights the promising potential of hierarchically assembled nanofiber scaffolds with dual growth factor gradients for wound repair and tissue regeneration applications.

Chitosan-polygalacturonic acid complex dressing improves diabetic wound healing and hair growth in diabetic mice

Chronic skin wounds decrease the quality of life of millions of diabetic patients worldwide. Chitosan has previously been shown to possess hemostatic properties, decrease inflammation, promote fibroblast proliferation, and hair growth. We developed a relatively low-cost polyelectrolyte complex (PEC) film dressing made of chitosan and polygalacturonic acid and tested it for its ability to accelerate diabetic wound healing. Genetically diabetic male mice were shaved on the dorsum, and one day later a 1 cm diameter full-thickness excisional wound was created. The PEC film was applied immediately after wounding and left in place for 14 days. Controls consisted of wounds treated with a fibrin gel. Wounds covered with the PEC film had closed completely by post-wounding day 42, while untreated wounds were only half-way closed. Histological analysis of wounds confirmed that PEC-treated wounds had fully re-epithelialized, while control wounds lacked a continuous epidermis at the wound center. We also observed that the area of skin under the PEC film experienced much more rapid hair growth. Histologically, there were significantly more hair follicles around the scar area (p < 0.05) in the PEC-treated group as compared to the control group. Thus, chitosan-polygalacturonic acid PEC films can accelerate both wound healing and hair growth in diabetic mice, and should be further investigated as a potential future treatment for diabetic chronic wounds.

Quality and performance indicators for wound management towards value-based healthcare

Outpatient services and specialized wound care clinics have become an expanding practice worldwide, which may be related to the increased life expectancy, rise in chronic diseases, favoring the occurrence of vascular and diabetic ulcers, as well as prolonging their treatment and delaying improvement. The high costs and risks associated with hospitalization lead to the patient being referred to a specialized wound center for continued treatment. The adoption of value-based healthcare models seeks cost reduction but primarily focuses on improving patient health outcomes. Its design and implementation depend on data that allows for measuring the health outcomes and costs of care for each patient and utilizing that information to drive continuous improvements. This study aims to propose quality and performance indicators for becoming a standard practice in specialized nursing services in wound care to enable the adoption of value-based healthcare models. The consultation of 19 experts through the Delphi method enabled the systematic organization of a large number of indicators identified in the literature into 8 categories and 43 specific indicators.

Assessing Nutrition Status in an Outpatient Wound Center: A Feasibility Study.

To explore the feasibility of using the Patient-Generated Subjective Global Assessment (PG-SGA) to assess the nutrition status of patients with chronic wounds receiving care in an outpatient wound clinic. The PG-SGA was administered to a single cohort convenience sample of adults with chronic wounds who presented to an outpatient wound clinic. The authors performed univariate descriptive analyses and calculated interrater reliability. Nutrition assessments were completed with 15 clinic patients. Patients required an average of 6.5 minutes (range, 3.5-10 minutes) to complete their component of the PG-SGA, exceeding the target goal of 5 minutes or fewer. Dietitians required an average of 2 minutes per patient to complete the professional component of the PG-SGA (physical examination). The nutrition assessment process was rated highly favorable. Resources to conduct the study at the site were available 100% of the time. The PG-SGA demonstrates promise for use in the chronic wound population and could be incorporated into clinical care in settings equipped with appropriate and adequate resources. The complexities of workforce stability and resource availability, in addition to the ongoing need to be responsive to patient challenges, must be acknowledged in the planning of future studies.

A Clinical Trial Design for Evaluating Topical Antimicrobials in Chronic Wounds: The BLEU Trial.

Chronic wound management is a global challenge. Millions of patients suffer from nonhealing ulcers and health systems are overwhelmed by the growing demand for treatment. Despite the prevalence of chronic wounds, the emergence of wound centers and specialized physicians is a recent phenomenon. Likewise, clinical research in wound healing is in its infancy. To date, many of the products in wound care have little or no clinical evidence. The field needs standardized clinical trial design, endpoints recognized by clinicians and payers, and improved overall clinical evidence. Wound healing is impeded by the presence of bacterial biofilms, which exist in most chronic wounds. It is not surprising that biofilm disruption is the focus of wound management and essential to the healing process. Multiple laboratory and preclinical studies demonstrate promising efficacy of several antimicrobials in treating biofilms; however, the field lacks in vivo clinical studies. In addition, a standardized trial design to evaluate efficacy of antimicrobials in chronic wounds does not exist. The advent of new diagnostic technologies, such as fluorescence imaging, has led to clinical trial designs that are reliable, easier to conduct, and cost efficient. The protocol presented here describes a randomized controlled double-blind trial designed to evaluate antiseptics in chronic wounds.

Dynamic optical coherence tomography of chronic venous ulcers.

Chronic ulcers, especially venous leg ulcers, are a major burden on the healthcare system. To date there are only few non-invasive established procedures for evaluation of blood perfusion in wounds. Dynamic optical coherence tomography (D-OCT) provides images of the skin's superficial vascularisation. This study aims to investigate if and how the D-OCT measurement of chronic wounds can provide new information about the vascularisation during the healing process. We examined 16 venous ulcers over 16 weeks and evaluated the vessel morphology and density using D-OCT at the wound bed, borders, two centimetres adjacent to the wound und at non-ulcerated skin on the contralateral leg. In D-OCT scans clumps were unique and the most common vessel type in the wound area of venous ulcers, whereas lines and serpiginous vessels were the most common in non-ulcerated skin. At the wound border mottle and cluster patterns occurred more frequently. Healthy skin showed a significant increase of mesh pattern. Vessel density significantly increased at the wound area compared to non-ulcerated skin. During the healing process the wound border showed the most vascular changes while only an increase in curves was observed in the wound centre. Non-healing wounds had fewer dots and blobs at the borders, fewer dots, coils, clumps, lines and serpiginous vessels at the centre and fewer dots in adjacent skin. Temperature analysis showed higher temperatures in non-ulcerated skin, followed by the wound margin and centre. Non-healing wounds showed the lowest temperatures in the wound centre. These results highlight the non-invasive use of D-OCT for the examination and monitoring of wound healing in chronic venous ulcers. D-OCT imaging of blood vessels may offer the potential to detect disorders of wound healing at an early stage, differentiate ulcers of different genesis and to tailor more individualized, patient-oriented therapy.

Financial toxicity of hidradenitis suppurativa: A single-center experience at an urban wound-care clinic.

Hidradenitis suppurativa (HS), is a chronic inflammatory skin disorder that confers a substantial financial burden to patients. The aim of the current study was to assess the patient-reported financial impact of HS. Patients presenting to a wound center between 2010 and 2021 were retrospectively reviewed. Demographics, comorbidities, and disease characteristics were collected. The financial impact of HS was assessed via the Comprehensive Score for Financial Toxicity - Functional Assessment of Chronic Illness Therapy (COST-FACIT) version 2 and investigator-generated surveys. Of 199 patients contacted, 27.1% (n = 54) completed the survey. The majority were women (77.8%, n = 42) and had private health insurance (n = 30; 55.6%). Most patients (66.7%, n = 36) had Hurley stage III disease. Mean follow-up was 2.3 + 2.8 years. The overall COST score was 19.7 + 12.4, indicating grade 1 financial toxicity (FT). Grade 0 FT was reported in 31.5% (n = 17) of patients, grade 1 in 37.0% (n = 20), grade 2 in 27.8% (n = 15), and grade 3 in 3.7% (n = 2). The mean self-reported 12-month out-of-pocket cost and credit scores were $2250 + 3269.24 and 674.6 + 95.3, respectively. Patients with private insurance had lower FT compared with Medicaid and Medicare (p = 0.003). Higher out-of-pocket costs were positively correlated with FT (p = 0.042), while higher credit scores were negatively correlated (p = 0.003). Patients with HS lesions in three or more anatomic regions reported the highest FT (p = 0.031). HS is a debilitating skin disorder that affects the livelihood of patients in a multifaceted manner. These patient-reported outcomes highlight the impact that HS has on an individual's financial security, calling for further attention to this vulnerable population.

Electrotaxis evokes directional separation of co-cultured keratinocytes and fibroblasts

Bioelectric communication plays a significant role in several cellular processes and biological mechanisms, such as division, differentiation, migration, cancer metastasis, and wound healing. Ion flow across cellular walls leads to potential gradients and subsequent formation of constant or time-varying electric fields(EFs), which regulate cellular processes. An EF is natively generated towards the wound center during epithelial wound healing, aiming to align and guide cell migration, particularly of macrophages, fibroblasts, and keratinocytes. While this phenomenon, known as electrotaxis or galvanotaxis, has been extensively investigated across many cell types, it is typically explored one cell type at a time, which does not accurately represent cellular interactions during complex biological processes. Here we show the co-cultured electrotaxis of epidermal keratinocytes and dermal fibroblasts with a salt-bridgeless microfluidic approach for the first time. The electrotactic response of these cells was first assessed in mono-culture to establish a baseline, resulting in the characteristic cathodic migration for keratinocytes and anodic for fibroblasts. Both cell types retained their electrotactic properties in co-culture leading to clear cellular partition even in the presence of cellular collisions. The methods leveraged here pave the way for future co-culture electrotaxis experiments where the concurrent influence of cell types can be thoroughly investigated.

Mutual repression between JNK/AP-1 and JAK/STAT stratifies senescent and proliferative cell behaviors during tissue regeneration.

Epithelial repair relies on the activation of stress signaling pathways to coordinate tissue repair. Their deregulation is implicated in chronic wound and cancer pathologies. Using TNF-α/Eiger-mediated inflammatory damage to Drosophila imaginal discs, we investigate how spatial patterns of signaling pathways and repair behaviors arise. We find that Eiger expression, which drives JNK/AP-1 signaling, transiently arrests proliferation of cells in the wound center and is associated with activation of a senescence program. This includes production of the mitogenic ligands of the Upd family, which allows JNK/AP-1-signaling cells to act as paracrine organizers of regeneration. Surprisingly, JNK/AP-1 cell-autonomously suppress activation of Upd signaling via Ptp61F and Socs36E, both negative regulators of JAK/STAT signaling. As mitogenic JAK/STAT signaling is suppressed in JNK/AP-1-signaling cells at the center of tissue damage, compensatory proliferation occurs by paracrine activation of JAK/STAT in the wound periphery. Mathematical modelling suggests that cell-autonomous mutual repression between JNK/AP-1 and JAK/STAT is at the core of a regulatory network essential to spatially separate JNK/AP-1 and JAK/STAT signaling into bistable spatial domains associated with distinct cellular tasks. Such spatial stratification is essential for proper tissue repair, as coactivation of JNK/AP-1 and JAK/STAT in the same cells creates conflicting signals for cell cycle progression, leading to excess apoptosis of senescently stalled JNK/AP-1-signaling cells that organize the spatial field. Finally, we demonstrate that bistable separation of JNK/AP-1 and JAK/STAT drives bistable separation of senescent signaling and proliferative behaviors not only upon tissue damage, but also in RasV12, scrib tumors. Revealing this previously uncharacterized regulatory network between JNK/AP-1, JAK/STAT, and associated cell behaviors has important implications for our conceptual understanding of tissue repair, chronic wound pathologies, and tumor microenvironments.