Mohs Micrographic Surgery for Invasive Melanoma Allows for Tissue Preservation Compared With Wide Local Excision: A Retrospective Cohort Study.

BACKGROUND: While increasing evidence supports the safety and effectiveness of immunohistochemistry-assisted Mohs micrographic surgery (MMS) for superficially invasive melanoma, there is a paucity of the literature investigating its effect on final defect size. OBJECTIVE: To evaluate the tissue sparing effect of MMS for melanoma. MATERIALS AND METHODS: Three hundred and twenty-eight patients with early-stage (T1a/T1b) cutaneous melanomas treated with MMS from January 2008 to December 2018 were evaluated. Measured defect sizes after Mohs tumor extirpation were compared with anticipated defect size that would result from standard-margin wide local excision (WLE). Average actual versus anticipated defect areas were compared using a paired t-test (95% confidence intervals). RESULTS: The following groups demonstrated a significantly smaller defect area for MMS-treated tumors when compared with anticipated standard-margin WLE defect: All tumors combined (13.8 cm2 vs 10.4 cm2, p < .001), tumors requiring 1 stage (13.6 cm2 vs 10.1 cm2,p < .001), and tumors requiring 2 stages (13.2 cm2 vs 10.5 cm2, p = .004). The majority of patients (83.5%, n = 274) achieved clear margins with 1 stage. CONCLUSION: Immunohistochemistry-assisted MMS for early-stage invasive melanoma is associated with smaller final defect size and overall tissue sparing effect compared with standard WLE margins.

Risk factors associated with tumor upstaging in melanomas treated with Mohs micrographic surgery with melanocytic immunohistochemistry.

Background: Mohs micrographic surgery with melanocytic immunohistochemistry (MMS-I) is increasingly utilized for special site melanoma treatment. Yet, frequency and risk factors associated with upstaging of all-stage cutaneous melanomas treated with MMS-I remain undefined. Objective: Determine upstaging frequency and factors associated with tumor upstaging for all-stage melanomas treated with MMS-I. Methods: In this retrospective, single-center case series, all cases of invasive and in situ melanoma treated with MMS-I between 2008 and 2018 were reviewed. Patient and tumor characteristics were recorded and compared between tumors that were and were not upstaged from their initial T stage. Results: Of the 962 melanoma MMS-I cases identified, 44 (4.6%) were upstaged, including 5.6% of in situ and 2.5% of invasive tumors. Risk factors for upstaging included lack of excisional intent at the time of initial biopsy (P < .01), nonlentigo maligna subtype (P = .03), female sex (P = .02), and initial in situ diagnosis (P = .03). Nonstatistically significant characteristics evaluated included patient age (P = .97), initial Breslow depth (P = .18), and biopsy type (P = .24). Limitations: Retrospective study design. Conclusions: All-stage cutaneous melanomas treated with MMS-I are associated with low upstaging rates. Tumor upstaging is associated with lack of excisional intent, female sex, and in situ tumors.

Results of Patch Testing to Botanicals: Review of the Mayo Clinic Experience Over 2 Decades (1997-2017).

Background: Botanicals are increasingly incorporated into skincare products. Although allergic contact dermatitis due to botanicals is recognized, data describing the prevalence of positive patch tests to botanicals are sparse. Objective: To report the Mayo Clinic experience of patch testing to selected botanical products in the standard, extended standard, fragrance, and plant series. Methods: IRB-approved retrospective study of the Mayo Clinic experience with patch testing to botanicals from 1997 to 2017. Results: In total, 12,169 people were patch tested to botanicals in the standard, extended standard, fragrance, and plant series; 4032 were men and 8137 were women. The mean age of the population tested was 54 (standard deviation 17.7) years. Almost 11% (1320/12,169) of the patch-tested population exhibited positive reactions to at least 1 botanical agent. Myroxylon pereirae resin 25% was the most common positive allergen in the series. Patients who had positive reactions to at least 1 botanical agent were more (19.8%) likely to have a positive reaction to at least 1 additional botanical than those patients who did not have any positive tests. Most patients presented with generalized involvement (334) or involvement of the hands (284) or face (232). Conclusion: Physicians should be aware of the high prevalence of allergic contact dermatitis and patch test positivity associated with botanical products.

Bridging the gap in BASCULE syndrome: A retrospective case series of a recently described clinical entity.

BACKGROUND: Bier anemic spots, cyanosis with urticaria-like eruption (BASCULE) syndrome is a recently described entity with episodic urticarial lesions and white anemic halos on a background of erythrocyanosis, commonly affecting the lower extremities. Possible association with autonomic dysfunction remains poorly understood. Existing publications are limited, but the condition is suggested as highly underrecognized. OBJECTIVE: To further characterize clinical and epidemiologic data for BASCULE syndrome. METHODS: We performed an IRB-approved retrospective chart review on patients with BASCULE syndrome evaluated at Mayo Clinic from April 2021 to November 2022. RESULTS: A total of 17 patients were identified (13 female, 4 male). Median age of onset was 12 years (range 9-17). Lower extremities were involved in all patients (17). Most patients were symptomatic with pruritus (8) or burning pain (8); three were asymptomatic. Triggers were standing (11), hot showers or hot environments (7), or no clear trigger (4). Autonomic dysfunction was present in 10 patients. Treatment responses were observed from propranolol (3) and high-dose cetirizine (1). CONCLUSION: Novel epidemiologic data from 17 pediatric and young adult patients with BASCULE syndrome further supports an association with autonomic dysfunction and suggests a higher prevalence than previously acknowledged.

Decoding information about cognitive health from the brainwaves of sleep.

Sleep electroencephalogram (EEG) signals likely encode brain health information that may identify individuals at high risk for age-related brain diseases. Here, we evaluate the correlation of a previously proposed brain age biomarker, the "brain age index" (BAI), with cognitive test scores and use machine learning to develop and validate a series of new sleep EEG-based indices, termed "sleep cognitive indices" (SCIs), that are directly optimized to correlate with specific cognitive scores. Three overarching cognitive processes were examined: total, fluid (a measure of cognitive processes involved in reasoning-based problem solving and susceptible to aging and neuropathology), and crystallized cognition (a measure of cognitive processes involved in applying acquired knowledge toward problem-solving). We show that SCI decoded information about total cognition (Pearson's r = 0.37) and fluid cognition (Pearson's r = 0.56), while BAI correlated only with crystallized cognition (Pearson's r = - 0.25). Overall, these sleep EEG-derived biomarkers may provide accessible and clinically meaningful indicators of neurocognitive health.

Evaluating Feasibility, Value and Characteristics of an Intergenerational Friendly Telephone Visit Program During the Covid-19 Pandemic.

OBJECTIVE: Volunteer organizations offer telephone outreach to older adults to relieve feelings of loneliness and to promote emotional well-being, though the feasibility, perceived value, and characteristics of the participant experience of these community interventions have not been well-studied. We examined these elements of an intergenerational college-based telephone call program during the Covid-19 pandemic. METHODS: Community-dwelling older adults and undergraduate volunteers engaged in eight, weekly, 30-minute, unscripted telephone conversations. Feasibility criteria included enrollment, retention, and attendance rates. A rapid qualitative analysis of program evaluation responses was used to extract themes related to participants' experiences of the intervention. RESULTS: Ten older adults (mean age [range] 74.53 [70-84] years, 88% women) and nine undergraduates were enrolled from February to August 2021, achieving recruitment targets and enrollment rates of 76.9% and 90%. Seven out of the 10 enrolled dyads completed the full series of eight telephone conversations and qualitative assessments over an average of 10.5 weeks. Most older adults who completed the call schedule valued the conversations as a source of social connection, noting the mutuality, respect, and broadened perspective that characterized their intergenerational relationships. Undergraduates described value in giving to others and in conversations that stimulated personal reflection and feelings of closeness. Undergraduates frequently described their experience as novel and broadening of their perspectives. CONCLUSION: Though study completion rate and participant experience varied across dyads, we found qualitative evidence of perceived value, active relationship-building and broadened perspectives among many older adults and undergraduates who completed an intergenerational telephone program.

Association of BRAF V600E Status of Incident Melanoma and Risk for a Second Primary Malignancy: A Population-Based Study.

Mutations of the BRAF oncogene occur in both melanomas and several other cancers. Our objective was to determine if mutant BRAF V600E expression in a population-based cohort of patients with melanoma was associated with the development of a second primary malignancy of any type. Using the resources of the Rochester Epidemiology Project, we retrospectively identified 380 patients aged 18 to 60 years who were diagnosed with an incident melanoma from 1970 through 2009. We reviewed individual medical records to identify second primary malignancies. We evaluated mutant BRAF V600E expression from available melanoma tissue specimens and assessed its association with the development of a second primary malignancy. BRAF V600E expression in melanomas is associated with an increased risk for basal cell carcinoma (BCC).

The Long-Term Public Health Impact of Social Distancing on Brain Health: Topical Review.

Social distancing has been a critical public health measure for the COVID-19 pandemic, yet a long history of research strongly suggests that loneliness and social isolation play a major role in several cognitive health issues. What is the true severity and extent of risks involved and what are potential approaches to balance these competing risks? This review aimed to summarize the neurological context of social isolation and loneliness in population health and the long-term effects of social distancing as it relates to neurocognitive aging, health, and Alzheimer's disease and related dementias. The full scope of the underlying causal mechanisms of social isolation and loneliness in humans remains unclear partly because its study is not amenable to randomized controlled trials; however, there are many detailed experimental and observational studies that may provide a hypothesis-generating theoretical framework to better understand the pathophysiology and underlying neurobiology. To address these challenges and inform future studies, we conducted a topical review of extant literature investigating associations of social isolation and loneliness with relevant biological, cognitive, and psychosocial outcomes, and provide recommendations on how to approach the need to fill key knowledge gaps in this important area of research.

Resident Training in Transitioning Youth With Epilepsy Into Adult Care.

OBJECTIVE: To appraise the current training of Neurology (N), Pediatric (P), and Med-Peds (MP) residents at MedStar Georgetown University Hospital (MGUH) in providing care to patients with epilepsy who are transitioning from pediatric to adult care. METHODS: Through an online questionnaire, we surveyed Neurology, Pediatric, and Med-Peds residents to assess their knowledge, confidence, and experience at transitioning youth with epilepsy to adult-oriented health care. RESULTS: N, P, and MP residents generally rated their knowledge and confidence at providing transition care to youth with epilepsy to be poor; however, P and MP residents rated higher in limited measures of knowledge and experience. CONCLUSION: Our appraisal of resident training in transitions care for youth with epilepsy has highlighted training elements in our institution that require attention for both adult and pediatric providers, leading to the formulation of an educational intervention that will promote experiential and multimodal approaches in this area.

The Impact of a Comprehensive Simulation-Based Training and Certification Program on Resident Central Venous Catheter Complication Rates.

INTRODUCTION: Millions of central venous catheters (CVCs) are placed annually in the United States, many by resident physicians. Simulation training has been proposed as a means to increase resident physician competence with CVC placement and decrease the incidence of line-associated mechanical complications. We aimed to evaluate the impact of a novel simulation-based CVC training program for resident physicians on CVC-associated mechanical complication rates. We hypothesized that the CVC-related mechanical complication rates would be lower among simulation-trained residents (STRs) compared with nonsimulation, traditionally trained residents (TTRs). METHODS: A retrospective chart review was performed of patients with a CVC placed by a resident physician between October 2014 and January 2017 at MedStar Georgetown University Hospital in Washington, DC. Incidence of CVC mechanical complications, including pneumothorax, hemothorax, arterial injury, or retained guidewire, were extracted from the electronic medical record and compared between STR and TTR cohorts. In contrast to TTRs who were trained to place CVCs in a supervised clinical setting, STRs underwent a CVC training program using online modules, a hands-on simulation training and testing checklist, and a series of successful supervised insertions before being credentialed to place lines independently. RESULTS: Nine hundred twenty-four CVCs placed by resident physicians during the study period were analyzed. There was no statistically significant difference in total mechanical complication rates between the STRs and TTRs in this study period (2.4% vs. 2.2%, P = 1). Simulation-trained residents were more likely to use ultrasound guidance when indicated during CVC insertion compared with TTRs (94.8% vs. 70.5%, P < 0.001). CONCLUSIONS: Mechanical complication rates associated with CVC insertion were similar between the simulation and TTRs and were consistent with previously published literature. These findings suggest that residents who underwent simulation training and certification demonstrated performance on par with more experienced TTRs. In addition, they were more likely to use best practices including ultrasound guidance in line placement.

Emergency department patients' perceptions of the efficacy and safety of opioid analgesics.

INTRODUCTION: Emergency department (ED) providers are on the forefront of the prescription drug crisis and understand-ing patient's perceptions of opioids may allow physicians to better address misconceptions. The aim was to determine the perceptions of ED patients regarding the efficacy and safety of opioid analgesics. METHODS: Cross-sectional study of a convenience sample of adults at a single urban academic ED. Patients completed a tablet-based survey regarding the efficacy and safety of opioid analgesics. RESULTS: Of the 715 subjects, the sample was predominantly black (80.4 percent), female (59.2 percent), and aged 18-59 years (76.8 percent). The majority (70.1 percent) of respondents reported pain as the reason for visit. Seventy-two percent had previously taken an opioid primarily for acute pain, found them effective for pain (88.2 percent), and would be willing to do so again (62.7 percent). Adverse effects made patients less likely to use them again (OR 0.703, [0.659-0.751]). Gender and age did not affect perceptions of efficacy and safety, but certain racial groups did (OR 1.08, [1.02 to 1.14], p < 0.05). Knowing someone who used opioids in a nonmedical manner did not impact willingness to use opioids. Many (54 percent) believed opioids to be as safe as nonopioid alternatives. The majority (78 percent) consid-ered prescription opioid abuse a public health problem, however underestimated the number of annual opioid-related deaths. CONCLUSION: The majority of ED patients had used opioids and considered the prescription drug crisis a public health problem. Through personal use or media coverage, the majority of participants considered opioids safe, even compared to nonopioid alternatives. Better understanding these viewpoints may improve patient-physician communication about analgesic treatment.

Chemo-immunotherapy combination after PD-1 inhibitor failure improves clinical outcomes in metastatic melanoma patients.

Management of PD-1 blockade resistance in metastatic melanoma (MM) remains challenging. Immunotherapy or chemotherapy alone provides limited benefit in this setting. Chemo-immunotherapy (CIT) has demonstrated favorable efficacy and safety profiles in lung cancer. Our pre-clinical study showed that in MM patients who have failed PD-1 blockade, the addition of chemotherapy increases CX3CR1+ therapy-responsive CD8+ T-cells with enhanced anti-tumor activity, resulting in improved clinical response. Here, we examined the clinical outcomes of CIT in MM patients after PD-1 blockade failure and the treatment-related changes in CX3CR1+ therapy-responsive CD8+ T-cells. We reviewed MM patients seen between January 2012 and June 2018 who failed anti-PD-1-based therapy and received subsequent CIT, immune checkpoint inhibitors (ICI) or chemotherapy alone. Overall survival (OS), objective response rate (ORR), event-free survival (EFS), and toxicities were assessed. Among 60 patients, 33 received CIT upon disease progression on PD-1 blockade. At a median follow-up of 3.9 years, the CIT group had a median OS of 3.5 years [95% confidence interval (CI) 1.7-NR] vs. 1.8 years (95% CI 0.9-2; P = 0.002) for those who received subsequent ICI (n = 9) or chemotherapy alone (n = 18), with ORR of 59% vs. 15% (P = 0.0003), respectively. The median EFS was 7.6 months (95% CI 6-10) following CIT vs. 3.4 months (95% CI 2.8-4.1; P = 0.0005) following ICI or chemotherapy alone. Therapy-responsive CX3CR1+CD8+ T-cells showed dynamic increase with successful CIT. CIT showed favorable clinical outcomes and acceptable safety profile in PD-1 blockade-resistant patients. CX3CR1+CD8+ therapy-responsive T-cells can be potentially used for monitoring disease response to CIT.

ACE inhibitor angioedema: characterization and treatment versus non-ACE angioedema in acute hospitalized patients.

Background: ACE angioedema has not been characterized in comparison with angioedema from other causes in acute hospitalized patients. Methods: We retrospectively compared ACE-angioedema and non-ACE angioedema patients from January 2013 to May 2017. Results: Of 855 cases screened, 575 met the inclusion criteria of angioedema diagnosis and an electronic medical record. Of these, 297 (51.7%) had ACE angioedema and 278 had angioedema from other causes, of these 31 who were taking an ACE inhibitor that was not considered to be the cause of angioedema (ACE other cause). At least 80% of cases in all groups were African American. Epinephrine was prescribed in 21% of ACE angioedema cases. One-third of patients in all groups were admitted to the ICU, and about 25% required intubation. Previous history of ACE inhibitor-induced angioedema was found in 63 of 278 non-ACE cause angioedema patients (23%) and in 23 (8%) in the ACE cause group. Conclusion: ACE angioedema was the cause of half of angioedema admissions over a 4.5-year period. Mortality, morbidity, and treatment did not differ between the groups. Patients on ACE inhibitors were often treated with medications known not to be effective for ACE angioedema. Over one-fourth of patients not taking an ACE inhibitor had a previous history of ACE angioedema, and 31 patients taking ACE inhibitors were diagnosed with non-ACE angioedema. Regardless of the etiology of angioedema, 25% of patients required airway protection in the form of intubation.

Anatomic Site-Specific Complication Rates for Central Venous Catheter Insertions.

BACKGROUND: Central venous catheter (CVC) complication rates reflecting the application of modern insertion techniques to a clinically heterogeneous patient populations are needed to better understand procedural risk attributable to the 3 common anatomic insertion sites: internal jugular, subclavian, and femoral veins. We sought to define site-specific mechanical and duration-associated CVC complication rates across all hospital inpatients. METHODS: A retrospective chart review was conducted over 9 months at Georgetown University Hospital and Washington Hospital Center. Peripherally inserted central catheters and tunneled or fluoroscopically placed CVC's were excluded. Mechanical complications (retained guidewire, arterial injury, and pneumothorax) and duration-associated complications (deep vein thrombosis or pulmonary embolism, and central line-associated bloodstream infections) were identified. RESULTS: In all, 1179 CVC insertions in 801 adult patients were analyzed. Approximately 32% of patients had multiple lines placed. Of 1179 CVCs, 73 total complications were recorded, giving a total rate of one or more complications occurring per CVC of 5.9%. There was no statistically significant difference between site-specific complications. A total of 19 mechanical complications were documented, with a 1.5% complication rate of one or more mechanical complications occurring. A total of 54 delayed complications were documented, with a 4.4% complication rate of 1 or more delayed complications occurring. There were no statistically significant differences between anatomic sites for either total mechanical or total delayed complications. CONCLUSIONS: These results suggest that site-specific CVC complication rates may be less common than previously reported. These data further inform on the safety of modern CVC insertion techniques across all patient populations and clinical settings.

Treatment of morphea with hydroxychloroquine: A retrospective review of 84 patients at Mayo Clinic, 1996-2013.

BACKGROUND: Few studies support treating morphea (localized scleroderma) with hydroxychloroquine. OBJECTIVE: To assess the efficacy of hydroxychloroquine treatment of morphea. METHODS: We conducted a retrospective study of 84 patients who had morphea and were treated with hydroxychloroquine monotherapy for at least 6 months at our institution from 1996 through 2013. The median times to initial and maximal responses were assessed. RESULTS: Of the 84 patients (median age at diagnosis, 29.5 years), 65 (77.4%) were female, 36 (42.9%) had a complete response to hydroxychloroquine, 32 (38.1%) had a partial response greater than 50%, 10 (11.9%) had a partial response less than or equal to 50%, and 6 (7.1%) had no response. The median time to initial response was 4 months, and the median time to maximal response was 12 months. Ten patients (11.9%) experienced adverse effects from hydroxychloroquine; the most common adverse effect was nausea (6 patients). LIMITATIONS: Retrospective study. CONCLUSIONS: Hydroxychloroquine is a valuable treatment for morphea because of its high response rate and low rate of adverse effects; however, prospective studies are needed to determine its true efficacy.