Reappraising Diabetic Foot Ulcers: A Focus on Mechanisms of Ulceration and Clinical Evaluation.

Diabetic foot ulcers (DFU) are one of the most devastating complications of diabetes as they have significant effects on patient morbidity and mortality. Since their first description in the 19th century, our understanding of DFU has evolved as we uncover the mechanisms that mediate ulceration. In this review, we aim to summarize the various pathways that lead to the development of DFU in order to reappraise physicians' understanding of these complex wounds. Relevant pathways include the following: (1) neuropathy (motor neuropathy, loss of protective sensation, and autonomic sympathetic dysfunction), (2) vascular disease (arterial ischemia, venous insufficiency, and microvascular changes), and (3) metabolism (signaling and immunological effects of hyperglycemia). We also discuss the clinical presentation of DFU and an evidence-based evaluation to assist clinicians in early identification and classification of these wounds to inform management of DFU. Finally, we summarize complications of DFU caused by the various pathways mediating ulceration and briefly overview DFU management in order to educate physicians about the potential risks if left untreated. A better understanding of the synergistic pathways leading to DFU is essential for clinicians to improve DFU diagnosis, tailor intervention, and mitigate significant patient morbidity and mortality.

Squamous and basal cell carcinoma with perineural invasion: pathophysiology and presentations.

Squamous and basal cell carcinomas with perineural invasion are typically difficult to treat because of their propensity to metastasize, their aggressive nature, and the concept of skip lesions. Perineural invasion is an under-recognized and underdiagnosed condition even though the literature points to its high rate of incidence in squamous cell carcinoma and a nonnegligible incidence rate in basal cell carcinoma. Perineural invasion has been linked to higher recurrence rates and poorer prognosis. This review has been written to aid clinicians in identifying and managing the condition as early as possible by describing the clinical and microscopic manifestations of perineural invasion.

Pediatric teledermatology: A review of the literature.

Skin complaints are common among pediatric patients, yet as of 2020, fewer than 400 board-certified pediatric dermatologists currently practice in the United States. Pediatric teledermatology may address barriers to dermatologic care in children, assisting with distant geographic locations and long wait times. A review of the literature was conducted to synthesize important features of teledermatology for pediatric dermatologists. We summarize types of telemedicine platforms, common dermatologic conditions seen by pediatric teledermatologists, diagnostic accuracy and concordance, and guidelines from the American Academy of Dermatology and the American Telemedicine Association regarding teledermatology. This report highlights the utility of pediatric telemedicine in both the outpatient and inpatient dermatology setting to increase access to high-quality dermatologic care.

Reporting regression with melanoma in situ: reappraisal of a potential paradox.

Melanoma in situ (MIS) is a form of radial growth phase melanoma in which the proliferation of malignant cells is confined to the epidermis. Histologic features are invaluable in recognition of MIS. Regression occurs when the host's immune system attacks the primary melanocytic tumor cells via tumor infiltrate lymphocytes, resulting in a fibrotic component. Various criteria have been proposed to assess the extent of histologic regression. Some authors define regression based on histologic features of the dermis, which is inappropriate for MIS. Specific dermatoscopic findings of regression in MIS have been reported including peppering, grey-blue areas, white areas, and blue-whitish veils. Many studies assess the impact of histologic regression on invasive melanoma prognosis, but no studies to-date have considered the effect of histologic regression exclusively in patients with MIS. The literature to-date does not suggest evaluation and management should be modified if histologic regression is present in MIS. Studies specifically investigating the effect of histologic regression on MIS prognosis are needed to inform evidence-based practices.

Grover disease: review of subtypes with a focus on management options.

Grover disease (GD) is a benign eruption that causes a papulovesicular rash on the trunk and proximal extremities. It often resolves spontaneously but can follow a more chronic and fluctuating course that may last several years. Although the etiology remains unknown, several associated triggers have been identified including heat and sweating, cool and dry air, renal failure, malignancy, and the initiation of several drugs. Since the disease tends to resolve on its own, management is aimed at disease prevention and symptomatic relief. First-line therapy includes topical steroids and vitamin D analogues with adjuvant antihistamines. In more severe cases that are refractory to less aggressive therapy, systemic corticosteroids, retinoids, and phototherapy may lead to successful resolution. Novel therapies are few and have little evidence but involve innovative use of light therapy and immune modulators. Herein, we review the literature and new trends of GD with a focus on established and novel treatments.

Diabetic Foot Ulcers: Appraising Standard of Care and Reviewing New Trends in Management.

Diabetic foot ulcers (DFU) are one of the most common diabetes complications and are associated with significant morbidity and mortality. Current DFU standard of care (SOC) involves four principles: (1) pressure relief, (2) debridement, (3) infection management, and (4) revascularization when indicated. Despite the current SOC, many DFU persist, warranting a new approach for the management of these complex wounds. This review aims to summarize the current SOC as well as the latest trends in adjunctive therapies that may become the new SOC in DFU management. These include negative pressure wound therapy and hyperbaric oxygen therapy, bioengineered skin substitutes, growth factors, shockwave therapy, and several others. These novel therapies have shown significant DFU clinical improvement among subsets of DFU patients. However, much of the literature comes from smaller trials with inconsistent patient selection and outcomes measured, making it difficult to assess the true clinical benefit of these treatments. While novel therapies are promising for the interdisciplinary approach to DFU management, many still lack sufficient evidence, and their efficacy remains to be determined.

Perianal Basal Cell Carcinoma Successfully Managed with Excisional Biopsy.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy in the United States and is often nonaggressive. Its location in the perianal region is very rare and it is estimated that only 0.08% of all BCCs occur in this region. Herein, we present a case of perianal basal cell carcinoma, nodular type. The diagnosis was made using excisional biopsy of a skin lesion. Immunohistochemical staining confirmed the diagnosis: it showed diffuse and strong positivity for smooth muscle actin (SMA) and monoclonal antibody BER-Ep4 and was negative for carcinoembryonic antigen (CEA), pancytokeratin (AE1/AE3), and epithelial membrane antigen (EMA). The treatment of choice has traditionally been local excision to clear margins but the newest guidelines recommend Mohs Micrographic surgery (MMS) or standard 4mm surgical margins for this high-risk BCC. Our patient was successfully treated using excisional biopsy without recurrence. In select patients with lesions smaller than 1cm, excisional biopsy may be sufficient to treat the disease and may be better tolerated than MMS and wider surgical margins. Literature review suggests a predisposition for perianal BCC in individuals susceptible to cutaneous malignancies. Therefore, any history of cutaneous malignancy should further prompt clinicians to examine nonsun exposed areas on full body skin exams.

Is substance use disorder more prevalent in patients with hidradenitis suppurativa?

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that disproportionately affects women and is associated with significant physical and psychosocial impact. Recent studies have reported an increased prevalence of substance abuse among patients with HS, including increased alcohol, opioid, and cannabis use. Whether substance use disorder is more prevalent among patients with HS is controversial because these data come from small studies and a major confounder is that patients with HS are often prescribed opioids for HS-associated pain. This review summarizes the current literature on substance use in HS to investigate whether substance use disorder is more likely in this patient population. We also highlight possible cofounders and areas of unmet need in HS that are potential causes of abuse, such as adequate pain control and impaired quality of life, and suggest opportunities for provider intervention. Evidence suggests that there is an increased prevalence of substance use disorder in patients with HS, but the full extent is still difficult to determine. However, with early screening and appropriate referrals to specialists, dermatologic providers may properly intervene and prevent substance use disorder in patients with HS.

Postprandial Insulin Response and Clearance Among Black and White Women: The Federal Women's Study.

Context: Postprandial hyperinsulinemia might be an important cardiometabolic risk determinant in black compared with white women. However, the contributions of insulin clearance and ß-cell function to racial differences in postprandial insulin response are unknown. Objective: To compare, by race and menopause, early insulin response to oral and intravenous glucose and to measure postprandial intact glucagon-like peptide 1 (GLP-1) concentrations, insulin clearance, and ß-cell function. Design and Participants: 119 federally employed women without diabetes [87 premenopausal (52 black, 35 white) and 32 postmenopausal (19 black, 13 white)] underwent an oral glucose tolerance test, insulin-modified frequently sampled intravenous glucose test (IM-FSIGT), and mixed meal tolerance test (MMTT). Outcome Measures: Early insulin response was measured as follows: (i) insulinogenic index (oral glucose tolerance test); (ii) acute insulin response to glucose (IM-FSIGT); and (iii) ratio of incremental insulin/glucose area under the curve in the first 30 minutes of the MMTT. Insulin clearance was assessed during the IM-FSIGT and MMTT. During the MMTT, intact GLP-1 was measured and ß-cell function assessed using the insulin secretion rate and ß-cell responsivity indexes. Results: Black pre-menopausal and postmenopausal women had a greater insulin response and lower insulin clearance and greater dynamic ß-cell responsivity (P ≤ 0.05 for all). No differences were found in the total insulin secretion rates or intact GLP-1 concentrations. Conclusions: Greater postprandial hyperinsulinemia in black pre-menopausal and postmenopausal women was associated with lower hepatic insulin clearance and heightened ß-cell capacity to rapid changes in glucose, but not to higher insulin secretion. The relationship of increased ß-cell secretory capacity, reduced insulin clearance, and ambient hyperinsulinemia to the development of cardiometabolic disease requires further investigation.

Variation in the Calculation of Allostatic Load Score: 21 Examples from NHANES.

After decades of resistance, there is now a genuine consensus that disease cannot be prevented or even successfully treated unless the role of stress is addressed alongside traditionally recognized factors such as genes and the environment. Measurement of allostatic load, which is quantified by the allostatic load score (ALS), is one of the most frequently used methods to assess the physiologic response to stress. Even though there is universal agreement that in the calculation of ALS, biomarkers from three categories should be included (cardiovascular, metabolic and immune), enormous variation exists in how ALS is calculated. Specifically, there is no consensus on which biomarkers to include or the method which should be used to determine whether the value of a biomarker represents high risk. In this perspective, we outline the approach taken in 21 different NHANES studies.

Glycated Albumin Identifies Prediabetes Not Detected by Hemoglobin A1c: The Africans in America Study.

BACKGROUND: Following immigration to the US, many Africans transition from a low-normal to a high-normal or overweight body mass index (BMI). This weight change is associated with a high rate of prediabetes in the nonobese. Studies in East Asians reveal that glycated albumin is effective in identifying prediabetes in nonobese Asians. Whether this is true in African immigrants is unknown. Therefore, we evaluated the ability of hemoglobin A1c (Hb A1c) and glycated albumin to detect prediabetes in nonobese (BMI <30 kg/m2) and obese (BMI ≥30 kg/m2) African immigrants. METHODS: Oral glucose tolerance tests (OGTTs) were performed in 236 self-identified healthy African immigrants [mean (SD) BMI 27.6 (4.4) kg/m2]. Prediabetes diagnosis was based on glucose criteria for the OGTT. Diagnostic sensitivity of Hb A1c and glycated albumin was determined by thresholds at the upper quartile for each [Hb A1c ≥5.7% (39 mmol/mol), glycated albumin ≥13.77%]. RESULTS: Based on glucose criteria for the OGTT, prediabetes was detected in 36% (85/236). BMI and Hb A1c were positively correlated (r = 0.22, P < 0.001), whereas BMI and glycated albumin were negatively correlated (r = -0.24, P < 0.001). Although the sensitivities of Hb A1c and glycated albumin were similar in nonobese immigrants (37% vs 42%, P = 0.75), prediabetes was detected in 21 nonobese Africans by glycated albumin alone, in 18 by Hb A1c alone, and in 4 by both tests. Therefore, sensitivity of the combined tests was better than for Hb A1c alone(72% vs 37%, P < 0.01). In the obese, Hb A1c was a much better diagnostic test than glycated albumin (64% vs 16%, P < 0.01) and combining the tests did not improve sensitivity (72% vs 64%, P = 0.50). CONCLUSIONS: Glycated albumin contributes by identifying prediabetes not detected by Hb A1c in nonobese African immigrants. ClinicalTrials.gov Identifier: NCT00001853.

A1C Combined With Glycated Albumin Improves Detection of Prediabetes in Africans: The Africans in America Study.

OBJECTIVE: Slowing the diabetes epidemic in Africa requires improved detection of prediabetes. A1C, a form of glycated hemoglobin A, is recommended for diagnosing prediabetes. The glycated proteins, fructosamine and glycated albumin (GA), are hemoglobin-independent alternatives to A1C, but their efficacy in Africans is unknown. Our goals were to determine the ability of A1C, fructosamine, and GA to detect prediabetes in U.S.-based Africans and the value of combining A1C with either fructosamine or GA. RESEARCH DESIGN AND METHODS: Oral glucose tolerance tests (OGTT) were performed in 217 self-identified healthy African immigrants (69% male, age 39 ± 10 years [mean ± SD], BMI 27.6 ± 4.5 kg/m(2)). A1C, fructosamine, and GA were measured. Prediabetes was diagnosed by American Diabetes Association criteria for glucose obtained from a 2-h OGTT. The thresholds to diagnose prediabetes by A1C, fructosamine, and GA were the cutoff at the upper tertile for each variable: ≥5.7% (39 mmol/mol) (range 4.2-6.6% [22.4-48.6 mmol/mol]), ≥230 µmol/L (range 161-269 µmol/L), and ≥13.35% (range 10.20-16.07%), respectively. RESULTS: Prediabetes occurred in 34% (74 of 217). The diagnostic sensitivities of A1C, fructosamine, and GA were 50%, 41%, and 42%, respectively. The P values for comparison with A1C were both >0.3. Combining A1C with either fructosamine or GA increased sensitivities. However, the sensitivity of A1C combined with fructosamine was not better than for A1C alone (72% vs. 50%, P = 0.172). In contrast, the sensitivity of A1C combined with GA was higher than for A1C alone (78% vs. 50%, P < 0.001). CONCLUSIONS: As individual tests, A1C, fructosamine, and GA detected ≤50% of Africans with prediabetes. However, combining A1C with GA made it possible to identify nearly 80% of Africans with prediabetes.