Minocycline-Induced Black Bone Disease in Foot and Ankle Surgery: A Case Report.

BACKGROUND: Bone and periarticular tissue discoloration can be an unexpected finding that is often disconcerting for surgeons and may alter surgical plans and overall patient management. Common causes of bone discoloration include infection, avascular necrosis, and bone inflammation. Minocycline-induced black bone disease is a rare and relatively benign abnormality encountered in foot and ankle surgery that can cause significant black, blue, and gray discoloration of bone. METHODS: Unanticipated intraoperative findings of diffuse black, blue, and gray bone discoloration during an elective forefoot operation raised concern for a metabolically malignant process and prompted the conversion of plans for a first metatarsophalangeal joint implant arthroplasty to a Keller arthroplasty. The plan for proximal interphalangeal joint arthroplasties of the lesser digits were continued as planned. Bone specimens were sent for pathologic analysis. RESULTS: Postoperative analysis identified chronic use of a minocycline for acne vulgaris. Pathologic analysis of the specimens ruled out malignant processes. Altogether, the data available led to the diagnosis of minocycline-induced black bone disease. Since the last follow-up, the patient has healed well without complications. CONCLUSIONS: Our case report underscores the importance of including the chronic use of tetracyclines in medical history intake during preoperative visits to assist the surgeon in intraoperative decision-making.

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.

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.

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.

Diagnosing osteomyelitis in the diabetic foot: a pilot study to examine the sensitivity and specificity of Tc(99m) white blood cell-labelled single photon emission computed tomography/computed tomography.

Diabetic foot ulceration poses a significant threat of osteomyelitis (OM) and subsequent amputation. The diagnosis of OM via imaging studies is difficult as radiographic findings do not present immediately and advanced imaging studies may be contraindicated or unavailable. A novel diagnostic tool has been developed which synthesises technetium-99 white blood cell-labelled single-photon emission computed tomography and computed tomography (Tc(99m) WBC labelled-SPECT/CT) imaging, effectively enhancing anatomic detail. The aim of this pilot study was to determine the validity and reliability of this novel imaging technique in patients with diabetic foot ulcers in a Veterans Affairs healthcare facility. A retrospective review was performed on consecutive patients who met the inclusion criteria (n = 14) and underwent Tc(99m) WBC-labelled SPECT/CT for suspected OM. Histopathologic analysis of bone specimen (when available) and International Working Group on the Diabetic Foot consensus criteria were used as a reference standard. The sensitivity and specificity of Tc(99m) WBC-labelled SPECT/CT were 87·50% [confidence interval (CI): 64·58-110·42%] and 71·43% (CI: 37·96-104·90%), respectively. Negative predictive value (NPV) and positive predictive value (PPV) were 83·33% (CI: 53·51-113·15%) and 77·78% (CI: 50·62-104·94%), respectively, with a likelihood ratio (LR) of 3·063 and an accuracy of 80%. These findings suggest Tc(99m) WBC-labelled SPECT/CT can be useful in imaging OM in patients with diabetic foot ulcers.

Painful prominences of the heel.

Heel pain is a common malady, with reported prevalence ranging from 4% to 21%. Referral to foot and ankle specialists for heel pain is also common, but patient awareness of the cause of heel pain may be limited. Many misconceptions about how heel exostoses relate to heel pain exist in the medical community and the general patient population, with many patients referred for or presenting with the simple complaint ''I have a heel spur.'' This article reviews the common exostoses of the heel, including plantar, lateral, and posterior spurs, with specific attention to the cause and treatments.