Julia Escandon

State of the art in topical wound-healing products

Summary: Chronic wounds represent a significant medical burden. Such wounds fail to normally progress through the stages of healing, often complicated by a proinflammatory milieu caused by increased proteinases, hypoxia, and bacterial burden. As a result, several modalities, such as dressings, antimicrobials, growth factors, and human skin substitutes, have been devised in an attempt to correct the chronic wound environment. This review addresses these modalities with a focus on evidence and randomized controlled trials.

High mortality in patients with chronic wounds

To the Editor: Chronic wounds have become a major public health issue in the United States and abroad. Patients with chronic wounds are often elderly, have cardiovascular disease and other comorbid conditions, and are at additional risk for further complications. This results in additional health care expenditures; for example, the United States alone spends

A prospective pilot study of ultrasound therapy effectiveness in refractory venous leg ulcers

25 billion annually related to chronic wounds and the demand for wound care is increasing. Specifically, diabetic foot ulcer complications have 5-year mortality rates similar to common types of cancer. A recent study from the Netherlands reported patients with diabetes mellitus who had foot ulcers to be at an increased risk for mortality compared with diabetics without foot ulceration (49% mortality over 10 years compared with 35.2% mortality—R 1.49). However, little is known about mortality for patients with other chronic wounds. We evaluated mortality in patients with chronic wounds to understand this better. We performed a retrospective cohort study of patients with chronic wounds treated in wound care centers and patients not treated in wound centers (matched by age, gender, and state of residence) using Centers for Medicare and Medicaid Services (CMS) data. Wound etiologies included venous leg ulcers, diabetic foot ulcers, and pressure ulcers. Using administrative data patients were followed for a 2-year period. We examined the incidence of wound-related deaths over a 2-year period. One thousand eight hundred fifteen patients with diabetic foot ulcers (DFU), pressure ulcers (PU) and venous leg ulcers (VLU) were included, 854 were treated at outpatient wound centers and 961 were treated in community practices. Fiftythree (52.6%) percent were men and the mean age of the group was 78 years old. Pressure ulcers accounted for 44% of the wounds and 84% were lower limb ulcers (Table 1). Comorbidities were common as two-thirds had cardiovascular disease, over half of patients had diabetes mellitus (DM), over 40% had peripheral arterial disease (PAD), one-quarter had either renal disease or neuropathy, and 4% had suffered a hip fracture. A higher frequency of comorbidities existed in patients treated in wound centers (Table 2). Of 1,815 patients, 28% (504 patients) died during the 2-year follow-up. Forty-six (2.5%) died in the hospital from a wound-related diagnosis (Table 3). No difference in death rate was noted in the different sites (Table 3), nor differences in the frequency of comorbidities or wound infection between deceased and surviving patients but differences existed in gangrene (RR51.93 95%, CI51.56–2.39); amputation (RR5 1.74 95%, CI51.35–2.25); and hospitalization for a woundrelated condition (RR51.95 95%, CI51.52–2.50) (Table 4). In summary we found that over one-quarter (28%) of wounded patients seen as outpatients died during a 2-year period. Drawn from both outpatient wound centers and community-based practices, they likely represent outpatients with wounds that are seen in the United States. As subjects of this study were outpatients and the majority of wounds were on the lower extremity, inpatients might have a different or even higher mortality with a greater percentage of sacral or ischial wounds. The population’s mean age was 75 years old and compared with similarly aged patients, death rates were much higher than the reported death rate for 75–79 year olds (4%), suggesting a higher risk of death in the wounded population. As expected patients studied had a high frequency of diseases that impede normal healing or may contribute to the

Potential Role of Meiosis Proteins in Melanoma Chromosomal Instability

Venous insufficiency is the most common cause of leg ulcers in the United States. Venous leg ulcers cost the health care system billions of dollars annually, and healing rates are less than 70% with standard of care; therefore, new therapies are needed to increase healing times and minimize associated costs. Non contact ultrasound therapy has been used to treat a variety of chronic wounds including venous leg ulcers, and it is thought that ultrasound has an effect on decreasing the bacterial count in wounds, although the exact mechanism of action of ultrasound is yet to be determined. We conducted an open labelled pilot study of 10 refractory venous ulcers of large size to determine the effect of non contact ultrasound on wound closure, bacterial counts, expression of inflammatory cytokines and pain reduction. We lacked a sham control group but we compared the baseline and end of treatment assessments and noted the differences. We found a significant reduction in wound area (P = 0·0039) over the 4‐week treatment period. We also found a decline in individual and total bacterial counts; however, these differences were not significant. For all patients, there was also a trend toward reduced inflammatory cytokine expression compared with baseline levels; however, this reduction did not reach statistical significance. Interestingly, there was a correlation between healing and change in cytokine expression, which showed statistically significance for tumour necrosis factor (TNF)‐αP = 0·0395, IL‐1a P = 0·0351, IL‐6 P = 0·0508, IL‐8 P = 0·0990. Pain as measured by the visual analogue scale (VAS) was reduced from 4 at the baseline to 2·7 by the end of the study. In conclusion, we found that patients treated with ultrasound therapy and compression therapy show clinical improvement over the course of 4 weeks and had a decrease in inflammatory cytokines, bacterial counts and pain.

Interstitial nephritis in melanoma patients secondary to PD-1 checkpoint inhibitor

Melanomas demonstrate chromosomal instability (CIN). In fact, CIN can be used to differentiate melanoma from benign nevi. The exact molecular mechanisms that drive CIN in melanoma have yet to be fully elucidated. Cancer/testis antigens are a unique group of germ cell proteins that are found to be primarily expressed in melanoma as compared to benign nevi. The abnormal expression of these germ cell proteins, normally expected only in the testis and ovaries, in somatic cells may lead to interference with normal cellular pathways. Germ cell proteins that may be particularly critical in CIN are meiosis proteins. Here, we review pathways unique to meiosis with a focus on how the aberrant expression of meiosis proteins in normal mitotic cells “meiomitosis” could impact chromosomal instability in melanoma and other cancers.

Quality assessment of tissue specimens for studies of diabetic foot ulcers

BackgroundImmune checkpoint inhibitors have become the first line therapy in melanoma treatment and their use is extending to other malignancies. However, we are still learning about immune side effects produced by these drugs and their severity especially in patients with history of inflammatory diseases.Case presentationWe present two cases of metastatic melanoma treated with nivolumab and pembrolizumab (anti PD-1). Both patients developed acute interstitial nephritis during immune checkpoint therapy. We emphasize the causal association between immune checkpoint inhibitors and the nephritis. The timing of drug administration and appearance of nephritis is suggestive of a causal relation between the checkpoint inhibitor therapy and this adverse event.ConclusionsAlthough uncommon, some side effects from checkpoint inhibitors can be severe and may need to be addressed with immunosuppression. Given the increasing frequency of immunotherapy use, awareness should be raised in regards to immune side effects and their appropriate management.

Postradiation Chronic Scalp Ulcer: A Challenge for Wound Healing Experts

Diabetic foot ulcers (DFUs) represent an important clinical problem resulting in significant morbidity and mortality. Ongoing translational research studies strive to better understand molecular/cellular basis of DFU pathology that may lead to identification of novel treatment protocols. Tissue at the non‐healing wound edge has been identified as one of major contributors to the DFU pathophysiology that provides important tool for translational and clinical investigations. To evaluate quality of tissue specimens and their potential use, we obtained 81 DFU specimens from 25 patients and performed histological analyses, immunohistochemistry and RNA quality assessments. We found that depth of the collected specimen is important determinant of research utility, and only specimens containing a full‐thickness epidermis could be utilized for immunohistochemistry and RNA isolation. We showed that only two‐thirds of collected specimens could be utilized in translational studies. This attrition rate is important for designs of future studies involving tissue specimen collection from DFU.

Refractory erythromelalgia of the ears: Response to mexiletine

For example, ionizing radiation, although beneficial for treating cancer, has negative effects on surrounding uninvolved tissues. Fragile and friable areas of damaged skin after radiation may lead to chronic, painful, and recalcitrant ulcers and, at times, bony changes. It may also result in more difficult healing after surgery and recurrence of the wound even with minor trauma. Despite improvements in radiation therapy techniques and equipment, chronic radiation ulcers are often resistant to conventional treatment modalities or advanced surgical options such as flap coverage or skin grafting and continue to be a therapeutic challenge. We present a case of a radiation ulcer treated using tissue engineered skin, discuss the pathophysiology of radiation-induced skin damage, and review the current management strategies.

Isolation of Mouse Hair Follicle Bulge Stem Cells and Their Functional Analysis in a Reconstitution Assay.

Erythromelalgia is a rare condition characterized by burning pain, erythema, swelling, and increased temperature usually in the extremities. We present an unusual presentation of erythromelalgia of the ears in a patient who has been refractory to multiple therapies and in whom relief of symptoms was achieved with the use of mexiletine. A review of clinical presentation, pathophysiology, and therapeutic options are presented.

Adalimumab treatment leads to reduction of tissue tumor necrosis factor-alpha correlated with venous leg ulcer improvement: a pilot study.

The hair follicle (HF) is a dynamic structure readily accessible within the skin, and contains various pools of stem cells that have a broad regenerative potential during normal homeostasis and in response to injury. Recent discoveries demonstrating the multipotent capabilities of hair follicle stem cells and the easy access to skin tissue make the HF an attractive source for isolating stem cells and their subsequent application in tissue engineering and regenerative medicine. Here, we describe the isolation and purification of hair follicle bulge stem cells from mouse skin, and hair reconstitution assays that allows the functional analysis of multipotent stem cells.