Apoptosis recognition receptors regulate skin tissue repair in mice.

Apoptosis and clearance of apoptotic cells via efferocytosis are evolutionarily conserved processes that drive tissue repair. However, the mechanisms by which recognition and clearance of apoptotic cells regulate repair are not fully understood. Here, we use single-cell RNA sequencing to provide a map of the cellular dynamics during early inflammation in mouse skin wounds. We find that apoptotic pathways and efferocytosis receptors are elevated in fibroblasts and immune cells, including resident Lyve1+ macrophages, during inflammation. Interestingly, human diabetic foot wounds upregulate mRNAs for efferocytosis pathway genes and display altered efferocytosis signaling via the receptor Axl and its ligand Gas6. During early inflammation in mouse wounds, we detect upregulation of Axl in dendritic cells and fibroblasts via TLR3-independent mechanisms. Inhibition studies in vivo in mice reveal that Axl signaling is required for wound repair but is dispensable for efferocytosis. By contrast, inhibition of another efferocytosis receptor, Timd4, in mouse wounds decreases efferocytosis and abrogates wound repair. These data highlight the distinct mechanisms by which apoptotic cell detection coordinates tissue repair and provides potential therapeutic targets for chronic wounds in diabetic patients.

Our skin is constantly exposed to potential damage from the outside world, and it is vital that any injuries are repaired quickly and effectively. Diabetes and many other health conditions can hamper wound healing, resulting in chronic wounds that are both painful and at risk of becoming infected, which can lead to serious illness and death of patients. After an injury to the skin, the wound becomes inflamed as immune cells rush to the site of injury to fight off infection and clear the wound of dead cells and debris. Some of these dead cells will have died by a highly controlled process known as apoptosis. These so-called apoptotic cells display signals on their surface that nearby healthy cells recognize. This triggers the healthy cells to eat the apoptotic cells to remove them from the wound. Previous studies have linked changes in cell death and the removal of dead cells to chronic wounds in patients with diabetes, but it remains unclear how removing dead cells from the wound affects healing. Justynski et al. used a genetic technique called single-cell RNA sequencing to study the patterns of gene activity in mouse skin cells shortly after a wound. The experiments found that, as the area around the wound started to become inflamed, the wounded cells produced signals of apoptosis that in turn triggered nearby healthy cells to remove them. Other signals relating to the removal of dead cells were also widespread in the mouse wounds and treating the wounds with drugs that inhibit these signals resulted in multiple defects in the healing process. Further experiments used the same approach to study samples of tissue taken from foot wounds in human patients with or without diabetes. This revealed that several genes involved in the removal of dead cells were more highly expressed in the wounds of diabetic patients than in the wounds of other individuals. These findings indicate that for wounds to heal properly it is crucial for the body to detect and clear apoptotic cells from the wound site. Further studies building on this work may help to explain why some diabetic patients suffer from chronic wounds and help to develop more effective treatments for them.

Transcriptional heterogeneity in human diabetic foot wounds.

Wound repair requires the coordination of multiple cell types including immune cells and tissue resident cells to coordinate healing and return of tissue function. Diabetic foot ulceration is a type of chronic wound that impacts over 4 million patients in the US and over 7 million worldwide (Edmonds et al., 2021). Yet, the cellular and molecular mechanisms that go awry in these wounds are not fully understood. Here, by profiling chronic foot ulcers from non-diabetic (NDFUs) and diabetic (DFUs) patients using single-cell RNA sequencing, we find that DFUs display transcription changes that implicate reduced keratinocyte differentiation, altered fibroblast function and lineages, and defects in macrophage metabolism, inflammation, and ECM production compared to NDFUs. Furthermore, analysis of cellular interactions reveals major alterations in several signaling pathways that are altered in DFUs. These data provide a view of the mechanisms by which diabetes alters healing of foot ulcers and may provide therapeutic avenues for DFU treatments.

Desmoplastic Fibroblastoma: A Case of a Rapidly Growing Mass in the Foot.

Desmoplastic fibroblastomas are benign and uncommon soft-tissue tumors. They are typically slow-growing, painless masses found in adult men. Rapidly growing masses have been previously reported, but are more rare. A 56-year-old man presented with a rapidly growing mass in his left foot, which was diagnosed as a desmoplastic fibroblastoma after pathologic evaluation. Although many case reports have been published in the dermatology literature, it is important to be aware of this benign neoplasm to avoid confusion with other rapidly growing malignant soft-tissue masses reported in the podiatry literature.

Degloving Traumatic Lesser Toe Injury Reconstruction with Full-Thickness Skin Graft from Partially Amputated Autologous Toe Donor Site: A Case Report.

Complex soft-tissue injuries consist of difficult traumatic injuries caused by high-energy mechanisms such as motor vehicle accidents, lawnmower injuries, and crush injuries from heavy objects. Many times, because of the high-energy trauma, there is significant damage to the soft tissue and underlying bone, leading to a complex situation for healing. In this case report, a 43-year-old woman presented with extensive degloving injury and open fractures of the forefoot resulting from a lawnmower accident. After extensive irrigation and debridement, wound closure was achieved using a full-thickness skin graft (FTSG). Although many case reports have been published about management of these complex soft-tissue injuries, there are no reports on using an autologous FTSG from a neighboring digit undergoing distal amputation for wound coverage. This report discusses the technique of using an autologous FTSG from an amputated specimen to achieve wound coverage with adequate limb salvage principles.

Intratendinous Ganglion Cyst of the Extensor Digitorum Longus: A Case Report.

Ganglion cysts have been recorded in many areas throughout the body. Intratendinous ganglion cysts in the foot are very rare. We present the case of 51-year-old woman with a recurrent right foot ganglion cyst. Surgical excision revealed a ganglion cyst in the tendon sheath of the extensor digitorum longus. It is important to be aware of potential tendon involvement for ganglion cysts, as surgeons must be prepared to perform tendon repairs in addition to mass excisions if the tendon is compromised.

Rare Presentation of Squamous Cell Carcinoma of the Foot in a Noncompliant HIV+ Patient.

INTRODUCTION: Squamous cell carcinoma (SCC) is most commonly found on sun-damaged skin and less often occurs on the toes and feet. CASE REPORT: A 41-year-old man with a history of human immunodeficiency virus and asthma, who had received highly active antiretroviral therapy for 7 years while incarcerated, presented to the emergency department with a primary SCC of the left foot with inguinal lymph node metastasis. The patient underwent a left foot transmetatarsal amputation; due to noncompliance, he underwent a below-the-knee amputation 17 days later as a result of surgical findings and extent of infection. The surgical site fully healed without further complications. The patient now has phantom limb pain of the left leg, sees oncology for palliative marijuana use, and refuses the recommended positron-emission tomography/computed tomography scan for completion of cancer staging. CONCLUSIONS: This case shows the importance of patient compliance and timely treatment of SCC and surgical wounds in an immunosuppressed individual.

A Case of Vascular Leiomyoma Causing Osseous Malformations in the Foot.

A vascular leiomyoma is a vascular soft tissue tumor that is relatively rare and benign. They usually occur as solitary lesions and are well encapsulated. The present study describes a unique case of vascular leiomyoma causing erosions of a metatarsal secondary to compression from the tumor. We present a female in her fourth decade of life with osseous malformations of the third metatarsal that became painful after an acute trauma to the foot.

An Investigation of Diabetes Knowledge Levels Between Newly Diagnosed Type 2 Diabetes Patients in Galway, Ireland and New York, USA: A Cross-Sectional Study.

Management of diabetes mellitus (DM) involves podiatrists as the primary practitioners engaged in prevention and treatment of lower limb pathology. Patients must first possess adequate knowledge to engage in effective self-management. A knowledge assessment of a DM cohort has never before been conducted in Ireland. The primary research objective was to determine the existence of gaps in specific areas of DM-related knowledge between type 2 DM (T2DM) patients in Galway (GW) and New York (NY). A cross-sectional study compared DM-related knowledge levels between 2 cohorts over a 10-week period. Participants were recently (<3 years) diagnosed with T2DM, were based in general podiatry clinics in GW or NY and had no current or previous diabetic foot ulceration (DFU) or other DM-related foot pathology. Participants were recruited by convenience sampling. A purpose-designed 28-item closed questionnaire was completed by both cohorts to assess knowledge differences. Fifty-two subjects were recruited (GW, n = 32; NY, n = 20). The mean age was 61 ± 10 years; 56% were male. Significant differences were found between cohorts relating to individual questions; specifically regarding knowledge of glycemic control (P = .002) and frequency of self-monitoring of blood glucose (P = .003). Inappropriate foot care practices across both cohorts were highlighted. No significant intercohort differences in particular survey sections were identified. The scores in the systemic and podiatric sections of the questionnaire highlight patterns of common health misconceptions and some highly inappropriate foot care practices respectively across the entire sample. In particular, the dearth of patient awareness regarding uncontrolled blood glucose and its relationship to DFU development, amputation, and associated morbidity is shown to be an area of concern; this must be addressed a priori.

Surface acoustic wave patch therapy affects tissue oxygenation in ischemic feet.

INTRODUCTION: Transcutaneous oxygen pressure (TcPO2) less than 30 mm Hg at the toe leads to local tissue hypoxia and nonhealing wounds. Studies regularly illustrate that TcPO2 values are strong predictors of healing and can accurately demonstrate altered levels when extremities have restricted blood flow. The objective of this study was to evaluate the effectiveness of surface acoustic wave (SAW) in ischemic feet on local tissue oxygenation. METHODS: Ten patients, ranging from 40-75 years of age and suffering from critical limb ischemia (CLI) were selected from a vascular surgery clinic to undergo evaluation with a PainShield SAW Patch device (NanoVibronix Inc, Melville, NY). Patients were treated once with 96 Khz of SAW for 30 minutes. All patients had an ankle brachial index of < 0.4 mm Hg. Two patients (patients 1 and 8) had necrosis of at least 2 toes on the affected limb and were given the device for nightly use for 1 month. RESULTS: Through usage of SAW there was a significant increase in all patients' saturation values. The recorded baseline in both patients with necrotic toes almost doubled and during usage there was still a measurable increase in oxygen saturation. In both of these patients the subjective pain measures dropped significantly. Pain, as assessed by the Visual Analog Scale, dropped from 9 to 2 for patient 1 and from 8 to 3 for patient 8. Patient 1 went from 5 methadone treatments per day to only 1 per day starting in week 3. Patient 8 did not change their pain medication regimen. CONCLUSION: Surface acoustic waves as delivered in this study had a positive effect on tissue oxygenation and saturation in ischemic feet. In lower extremities that are not surgical candidates or are either in the pre- or postsurgical environment, an SAW patch device is a good therapy in elevating the extremities' O2 saturation.

Onychomycosis in close quarter living review of the literature.

Onychomycosis is defined as a fungal infection of the nail bed and/or nail plate. The prevalence of onychomycosis has increased dramatically as a worldwide condition in the twentieth century due to occlusive footwear, global wars and natural migration. Risk factors generally leading to onychomycosis development include bodily spread of dermatophyte and non-dermatophyte tinea pedis, peripheral vascular disease, damaged nails via sports and trauma, older age, genetics, immunodeficiency and diabetes. Many publications discuss prevalence, symptoms and treatment of the disease in individual cases, hospitals or specific locations, but few strongly link the cause of onychomycosis to living environments. This is a review of the current literature on the prevalence of onychomycosis and its relationship to surrounding living environments of those infected. A Pubmed search was performed with 'onychomycosis'. Articles were selected based on the relevance to close quarter living environments. All ages can be affected with onychomycosis, ranging from children in boarding schools to elderly in nursing homes. Although not directly linking living environments to transmission and infection in all articles reviewed, onychomycosis was very prevalent in many different close quarter living settings, including within families, boarding schools, military quarters and nursing homes. This review demonstrates that various close quarter living environments are highly associated with increased transmission and infection with onychomycosis.