Diabetes is a systemic disease in which the body cannot regulate the amount of sugar, namely glucose, in the blood. High glucose toxicity has been implicated in the dysfunction of diabetic wound healing, following insufficient production (Type 1) or inadequate usage (Type 2) of insulin. Chronic non-healing diabetic wounds are one of the major complications of both types of diabetes, which are serious concerns for public health and can impact the life quality of patients significantly. In general, diabetic wounds are characterized by deficient chemokine production, an unusual inflammatory response, lack of angiogenesis and epithelialization, and dysfunction of fibroblasts. Increasing scientific evidence from available experimental studies on animal and cell models strongly associates impaired wound healing in diabetes with dysregulated fibroblast differentiation to myofibroblasts, interrupted myofibroblast activity, and inadequate extracellular matrix production. Myofibroblasts play an important role in tissue repair by producing and organizing extracellular matrix and subsequently promoting wound contraction. Based on these studies, hyperglycaemic conditions can interfere with cytokine signalling pathways (such as growth factor-β pathway) affecting fibroblast differentiation, alter fibroblast apoptosis, dysregulate dermal lipolysis, and enhance hypoxia damage, thus leading to damaged microenvironment for myofibroblast formation, inappropriate extracellular matrix modulation, and weakened wound contraction. In this review, we will focus on the current available studies on the impact of diabetes on fibroblast differentiation and myofibroblast function, as well as potential treatments related to the affected pathways.

Background. Locally advanced basal cell cancer is a rare and challenging clinical problem. Historically, these patients were treated with aggressive surgery or radiotherapy. Most sporadic basal cell carcinomas have somatic mutations in the hedgehog pathway. Oral hedgehog inhibitors induce rapid and often complete clinical responses in locally advanced basal cell tumors. Unfortunately, these responses are usually transient. We hypothesized that treatment failure represents persistence of drug resistant cells that could be eradicated by addition of localized radiotherapy. Materials and Methods. We performed a retrospective review of our patients with locally advanced basal cell cancer treated with sonidegib or vismodegib induction therapy who were treated with added superficial radiotherapy at the time of maximal response. Results. Twelve patients met inclusion criteria. All patients achieved a complete response following hedgehog inhibitor therapy with addition of radiotherapy. Progression-free survival at 40 months was 89%, with a median follow-up of 40 months. Relapses occurred in only 2 of 12 patients (16.6%). Nine patients experienced grade I-II toxicity from hedgehog inhibitor induction therapy (taste changes [3], weight loss [3], muscle cramps [3]). Eight patients experienced mild radiotherapy-induced skin toxicity during concurrent therapy. No patients had to discontinue treatment. Conclusion. Induction therapy with hedgehog inhibitors followed by addition of concurrent radiation therapy resulted in an extremely high clinical response rate with relatively minor and reversible toxicity. This gave a high rate of progression-free survival and a low disease-specific progression rate. Further prospective evaluation of this treatment approach is needed to confirm the apparent clinical activity. The Oncologist ;9999:• • Implications for Practice: Locally advanced basal cell cancers are challenging to treat. Previously, aggressive surgical resection or radiotherapy represented the best treatment options. Most basal cell cancers have somatic mutations in the hedgehog pathway. Oral inhibitors of this pathway produce rapid, but transient clinical responses. This study reports 12 patients treated with hedgehog inhibitor induction therapy to near-maximal response. Addition of concurrent involved field radiotherapy resulted in a very high complete response rate with minimal toxicity. There was prolonged progressionfree survival in 90% of patients. This study identified a novel treatment approach for patients with advanced basal cell carcinoma.

Background: There has been a significant increase in the volume of gender-affirming surgical (GAS) procedures over the past decade. The objective of this paper is to use online search data from Google Trends (GT) to describe national search trends for GAS procedures.Methods: GT was queried for search terms relating to GAS from January 2004 to February 2021. The 19 selected keywords covered a broad range of GAS topics. United States (US) search interest was collected as relative search volumes (RSVs) and then analyzed by geographic region. The number of plastic surgery providers offering GAS and academic surgery centers was collected from the World Professional Association for Transgender Health (WPATH) and Trans-health.com. RSVs were analyzed by metro area to determine the relationship between search demand and personal income. State Medicaid policies for transgender health services were also collected.Results: All search terms demonstrated a positive increase in RSVs over time except "sex reassignment surgery" and "penectomy". The Mountain/Pacific and East South Central/West South Central had the greatest search volume for GAS and most providers offering care. The East South Central/West South Central region ranked last for providers offering care, despite the relatively high search interest. This region also had no states with explicit Medicaid policies covering gender-affirming care. Metro areas in the top five for RSV but bottom quartile for per capita personal income were identified.Conclusions: Online search interest for GAS-related terms has increased. Search interest for GAS has regional variation and did not show a specific pattern with provider availability.

Understanding patient awareness of cleft lip and/or palate (CL/P) and evaluating demand for necessary procedures may serve to better target future efforts in global outreach. We utilized internet search query data from Google Trends for the terms: “cleft lip,” “cleft palate,” “cleft lip and palate,” “cleft surgery,” and “cleft repair” from January 2004 to January 2021. Relative search volumes (RSV) recorded for the top 5 highest displaying countries and top 3 available regions within those countries were compared against global outreach by Operation Smile and Smile Train, as measured by the number of patients treated. World Health Organization (WHO) indicators were used to validate the RSV values for each country and better understand the current infrastructure and need for cleft care in those countries. Globally, there was an increase in RSV for the terms “cleft lip,” “cleft palate,” “cleft repair,” and “cleft surgery” between 2004 and 2021. For “cleft lip,” the countries with the highest displaying RSVs included: Ghana (100%), Zimbabwe (97%), Nepal (78%), the Philippines (64%), and Kenya (52%). Countries with high RSVs and moderate to high WHO indicators included Ghana, Kenya, India, Nigeria, and Zimbabwe. Countries with high RSVs and poor WHO indicators included Nepal and Pakistan. Some countries had specific regions with high search demand that are not currently targeted for global outreach. Using Google Trends’ data may help find more feasible locations and targeted care for efforts in global outreach with better patient awareness and turnout where demand for CL/P is increasing.