Postoperative Complications After Interpolated Flap Repair for Mohs Defects of the Nose: A Multicenter Prospective Cohort Study.

BACKGROUND: Dermatologists perform most interpolated flaps after skin cancer resection. Prospective, multicenter data on complications after interpolated flap repair in this setting are limited. OBJECTIVE: To determine the rate of physician-reported complications after interpolated flap repair of the nose. METHODS: Multicenter, prospective cohort study of 169 patients undergoing 2-stage interpolated flap repair of post-Mohs nasal defects. Frequency of bleeding, infection, dehiscence, necrosis, hospitalization, and death in the 30 days after flap placement and flap takedown are reported. RESULTS: Patients experienced 23 complications after flap placement (13.61%) and 6 complications after flap takedown (3.55%) that were related to the surgical procedure. The most frequent complication after flap placement was bleeding (9, 5.33%, 95% confidence interval [CI]: 2.83%-9.82%). The most frequent complication after flap takedown was infection (5, 2.96%, 95% CI: 1.27%-6.74%). There was one hospitalization related to an adverse reaction to antibiotics. There were no deaths. CONCLUSION: Most complications after interpolated flap repair for post-Mohs defects of the nose are minor and are associated with flap placement. Interpolated flap repair for post-Mohs defects can be performed safely in the outpatient setting under local anesthesia.

Expanding the Histologic Spectrum of Sudden Conjunctivitis, Lymphopenia, and Rash Combined With Hemodynamic Changes.

ABSTRACT: Sudden conjunctivitis, lymphopenia, and rash combined with hemodynamic changes (SCoRCH) is a recently described hypersensitivity reaction to trimethoprim-sulfamethoxazole. To date, only 1 case of histologic findings in SCoRCH has been reported, revealing a superficial perivascular dermatitis. In this article, we present a 53-year-old woman with a four-day history of a widespread, confluent, erythematous, and dusky rash after exposure to trimethoprim-sulfamethoxazole. Histologic examination revealed a vacuolar interface dermatitis with several apoptotic keratinocytes at multiple levels of the epidermis, similar to an erythema multiforme-like presentation. As described in SCoRCH, our patient's clinical findings rapidly improved within 48 hours of presentation without treatment. This case adds to the current literature by identifying a newly described histopathological presentation of SCoRCH.

Pseudocarcinomatous Hyperplasia Masquerading as a Well-Differentiated Squamous Cell Carcinoma Associated With Primary Cutaneous Anaplastic Large-Cell Lymphoma.

ABSTRACT: Pseudocarcinomatous hyperplasia (PCH) is a reactive proliferation of the epidermis associated with CD30 + lymphoproliferative disorders. In this article, we report the case of a 42-year-old man who presented with a 10-year history of a solitary erythematous patch on the right thigh that progressed to an ulcerated, crusted plaque. Histologic examination revealed an infiltrate of atypical CD30 + lymphocytes consistent with primary cutaneous anaplastic large-cell lymphoma with overlying well differentiated keratinocyte hyperplasia akin to a well-differentiated invasive squamous cell carcinoma. This case demonstrates the phenomenon of pseudocarcinomatous hyperplasia mimicking features of invasive squamous cell carcinoma. It highlights the necessity of careful clinical correlation when diagnosing squamous cell carcinomas in younger patients on non-sun-exposed areas and the exclusion of accompanying known causes of pseudocarcinomatous hyperplasia.

Pembrolizumab-induced pseudoepitheliomatous eruption consistent with hypertrophic lichen planus.

Pembrolizumab, an anti-programmed cell death-1 (PD-1) antibody preparation, has been shown to induce various dermatologic adverse events which may present with delayed onset or even after discontinuation of therapy. We report a 78-year-old female patient with a stage II lung adenocarcinoma treated with pembrolizumab, who developed lichenoid eruptions and multiple cutaneous plaque/nodular eruptions as pseudoepitheliomatous hyperplasia, during and up to 2 months after discontinuation of pembrolizumab therapy. Multiple skin biopsies revealed epidermal hyperplasia with hyperkeratosis, hypergranulosis, diffuse to patchy lichenoid lymphocyte infiltrate with scattered eosinophils and neutrophils, confluent to scant dyskeratosis of the lower epidermis, minimal to overt invagination, and cystic proliferation of squamous epithelium to papillomatosis with hypergranulosis and keratosis. Overall, multiple patterns were present with similarities to lichenoid drug eruption, lichen planus, early invasive squamous cell carcinoma, early keratoacanthoma, and verruca. However, the findings ultimately supported a diagnosis of hypertrophic lichen planus. All the lesions resolved with oral prednisone, hydroxychloroquine, and topical triamcinolone acetonide ointment 0.1%. In summary, our case shows that pembrolizumab can induce lichenoid eruption with pseudoepitheliomatous hyperplasia, and these lesions can clinically and pathologically mimic early invasive squamous cell carcinomas or keratoacanthomas.

Antibiotic adherence in dermatologic surgery: a Multicenter prospective cohort study.

Understanding patient non-adherence to prescribed antibiotics can inform clinical practices, patient counseling, and antibiotic efficacy study design in dermatology. The primary objective was to determine the rate of and reasons for antibiotic non-adherence in the dermatologic surgery setting. The secondary objective was to test the applicability of previously studied survey questions for antibiotic non-adherence screening in the dermatologic surgery setting. Five academic outpatient dermatologic surgery centers across the United States conducted one multicenter prospective cohort study. Dermatologic surgery patients ≥ 18 years of age who were prescribed an antibiotic were included as part of this study. 15.2% (42/276) of patients did not adhere to their antibiotic regimen after dermatologic surgery. Most common reasons for incomplete antibiotic courses included forgotten antibiotics (42.9%,18/42) and side effects (28.6%, 12/42). Previously evaluated questions to identify and predict non-adherence had modest performance in the dermatologic surgery setting (Area under the curve of 0.669 [95% CI (0.583-0.754)]). Antibiotic non-adherence after skin surgery is prevalent and commonly due to reasons that physicians can address with patients.

Patient-Reported Nasal Function and Appearance After Interpolation Flap Repair Following Skin Cancer Resection: A Multicenter Prospective Cohort Study.

Objective: Among patients undergoing two-stage interpolated flap repair of nasal defects, nasal function, and appearance before surgery and at 16 weeks after flap takedown were compared using the Nasal Appearance and Function Evaluation Questionnaire (NAFEQ). Design: Multicenter prospective cohort study. Methods: Adult patients with a nasal skin cancer anticipated to require two-stage interpolation flap repair completed the NAFEQ before surgery, at 1 week after flap placement, 4 weeks after flap takedown, and 16 weeks after flap takedown. Results: One hundred sixty-nine patients were enrolled, with 138 patients completing both presurgical and 16-week post-takedown NAFEQs. Overall NAFEQ score increased by 1.09 points (1.91% improvement, confidence interval [95% CI -0.34 to 2.53]). NAFEQ functional subscale increased by 0.72 points (2.58% increase; 95% CI [0.10-1.35]) and appearance subscale increased by 0.37 points (1.28% improvement, 95% CI [-0.65 to 1.39]). Conclusion: At 16 weeks after flap takedown, patients' perceptions of their nasal function and appearance are similar to or slightly improved when compared with their presurgical assessments.

Complete Genome Sequences of Chop, DelRio, and GrandSlam, Three Gordonia Phages Isolated from Soil in Central Arkansas.

Chop, DelRio, and GrandSlam are phage with a Siphoviridae morphotype isolated from soil in Arkansas using the host Gordonia terrae 3612. All three are temperate, and their genomes share at least 96% nucleotide identity. These phage are assigned to cluster DI based on gene content similarity to other sequenced actinobacteriophage.

Partial synchronization of stochastic oscillators through hydrodynamic coupling.

Holographic optical tweezers are used to construct a static bistable optical potential energy landscape where a brownian particle experiences restoring forces from two nearby optical traps and undergoes thermally activated transitions between the two energy minima. Hydrodynamic coupling between two such systems results in their partial synchronization. This is interpreted as an emergence of higher mobility pathways, along which it is easier to overcome barriers to structural rearrangement.

Optical tweezers: a light touch.

Optical tweezers use focused laser light to manipulate microscopic particles. We discuss the underlying physics of the technique in terms of a gradient force exerted by the light on the particles. The versatility of optical tweezers is highlighted, in particular, we explain how spatial light modulators and various imaging methods have greatly enhanced their range of applications.

Water-mediated binding of agents that target the DNA minor groove.

Small molecule complexes with DNA that incorporate linking water molecules are rare, and the DB921-DNA complex has provided a unique and well-defined system for analysis of water-mediated binding in the context of a DNA complex. DB921 has a benzimidazole-biphenyl system with terminal amidines that results in a linear conformation that does not possess the appropriate radius of curvature to match the minor groove shape and represents a new paradigm that does not fit the classical model of minor groove interactions. To better understand the role of the bound water molecule observed in the X-ray crystal structure of the DB921 complex, synthetic modifications have been made in the DB921 structure, and the interactions of the new compounds with DNA AT sites have been evaluated with an array of methods, including DNase I footprinting, biosensor-surface plasmon resonance, isothermal titration microcalorimetry, and circular dichroism. The interaction of a key compound, which has the amidine at the phenyl shifted from the para position in DB921 to the meta position, has also been examined by X-ray crystallography. The detailed structural, thermodynamic, and kinetic results provide valuable new information for incorporation of water molecules in the design of new lead scaffolds for targeting DNA in chemical biology and therapeutic applications.

Patient Quality of Life After Interpolated Flap Repair of Nasal Mohs Surgery Defects: A Multicenter Prospective Cohort Study.

IMPORTANCE: Single-center studies have shown that patients report better skin cancer-specific quality of life (QOL) after Mohs micrographic surgery (MMS), but it is unclear whether this improved QOL applies to patients after MMS and complex reconstruction in cosmetically sensitive areas. OBJECTIVE: To evaluate patient QOL after MMS and interpolation flap reconstruction for patients with nasal skin cancers. DESIGN, SETTING AND PARTICIPANTS: This multicenter prospective survey study used the Skin Cancer Index (SCI), a validated, 15-question QOL questionnaire administered at 4 time points: before MMS, 1 week after flap placement, 4 weeks after flap takedown, and 16 weeks after flap takedown. Patients age 18 years or older with a nasal skin cancer who presented for MMS and were anticipated to undergo 2-stage interpolated flap repair by a Mohs surgeon were recruited from August 9, 2018, to February 2, 2020, at 8 outpatient MMS locations across the United States, including both academic centers and private practices. MAIN OUTCOMES AND MEASURES: Mean difference in overall SCI score before MMS vs 16 weeks after flap takedown. RESULTS: A total of 169 patients (92 men [54.4%]; mean [SD] age, 67.7 [11.4] years) were enrolled, with 147 patients (75 men [51.0%]; mean [SD] age, 67.8 [11.7] years) completing SCI surveys both before MMS and 16 weeks after flap takedown. Total SCI scores improved significantly 16 weeks after flap takedown compared with pre-MMS scores, increasing by a mean of 13% (increase of 7.11 points; 95% CI, 5.48-8.76; P < .001). All 3 SCI subscale scores (emotion, appearance, and social) improved significantly (emotion subscale, increase of 3.27 points; 95% CI, 2.35-4.18; P < .001; appearance subscale, increase of 1.65 points; 95% CI, 1.12-2.18; P < .001; and social subscale, increase of 2.10 points; 95% CI, 1.55-2.84; P < .001) 16 weeks after flap takedown compared with pre-MMS. CONCLUSIONS AND RELEVANCE: Removal of a nasal skin cancer and repair of the resulting defect can be distressing for patients. However, this cohort study suggests that physicians referring patients for MMS can be reassured that their patient's QOL will improve on average after surgery, even when a complex reconstruction is required.

Risk for deep fungal infections during IL-17 and IL-23 inhibitor therapy for psoriasis.

Psoriasis is an inflammatory disease with both skin and joint manifestations. Focused biologics have been developed to target specific cytokines implicated in psoriasis and are becoming increasingly utilized. Recently, the advent of newer biologics, including IL-17, IL-12/IL-23, and IL-23 inhibitors, have garnered interest as promising treatments for psoriasis and other inflammatory conditions. Although IL-17 and IL-23 have been studied in the pathophysiology of psoriasis, they also play a central role in immunologic defenses, including those against fungi. Therefore, use of these interleukin inhibitors may theoretically impair the immune system against deep fungal infections. We reviewed the available literature investigating the risk for invasive fungal infections in patients treated with IL-17 and IL-23 inhibitors for psoriasis or other inflammatory conditions. Randomized controlled trials (RCTs), including extended trials and clinical trials, were reviewed, and we found that although there was a small number of patients who developed superficial candidiasis, there were no reports of invasive fungal disease. Although these results support the safety and the low risk for deep fungal infection with these biologics, caution is still warranted, as these medications are relatively new. Appropriate screening and management of fungal disease should still be practiced when utilizing these medications in the treatment of psoriasis and other inflammatory conditions.

Risk of herpes zoster with IL-17 inhibitor therapy for psoriasis and other inflammatory conditions.

Background: Psoriasis is a chronic inflammatory skin disease that has been associated with a significantly higher risk of herpes zoster (HZ). Several newer biologics such as secukinumab, ixekizumab, and brodalumab inhibit IL-17 and have been highly effective for treatment of psoriasis. However, adverse events related to the immunosuppressive properties of these biologics have been observed.Methods: This review aims to synthesize and evaluate the literature investigating the risk of HZ in patients treated with IL-17 inhibitors, with a focus on psoriasis patients. We performed searches using the PubMED database with the following search terms: 'psoriasis,' 'herpes zoster,' 'secukinumab,' 'ixekizumab,' 'brodalumab,' 'IL-17,' 'anti-IL-17,' and 'safety.' Clinical trials, cohort studies, review articles, and meta-analyses were evaluated.Results: Studies did not detect a higher risk of HZ infections in psoriasis patients treated with IL-17 inhibitors when compared to those treated with placebo or other therapies. Studies of IL-17 inhibitors for other indications including psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and asthma yielded similar results.Conclusion: IL-17 inhibitors do not appear to increase risk of HZ. However, IL-17 inhibitors are relatively new medications, and further long-term data may be necessary to confirm this finding. Nevertheless, HZ vaccination should be considered on a case-bycase basis prior to initiating IL-17 therapy.

Unmet Clinical Need: Developing Prognostic Biomarkers and Precision Medicine to Forecast Early Tumor Relapse, Detect Chemo-Resistance and Improve Overall Survival in High-Risk Breast Cancer.

Chemo-resistant breast cancer is a major barrier to curative treatment for a significant number of women with breast cancer. Neoadjuvant chemotherapy (NACT) is standard first- line treatment for most women diagnosed with high-risk TNBC, HER2+, and locally advanced ER+ breast cancer. Current clinical prognostic tools evaluate four clinicopathological factors: Tumor size, LN status, pathological stage, and tumor molecular subtype. However, many similarly treated patients with identical residual cancer burden (RCB) following NACT experience distinctly different tumor relapse rates, clinical outcomes and survival. This problem is particularly apparent for incomplete responders with a high-risk RCB classification following NACT. Therefore, there is a pressing need to identify new prognostic and predictive biomarkers, and develop novel curative therapies to augment current standard of care (SOC) treatment regimens to save more lives. Here, we will discuss these unmet needs and clinical challenges that stand in the way of precision medicine and personalized cancer therapy.

High-resolution crystal structure of the intramolecular d(TpA) thymine-adenine photoadduct and its mechanistic implications.

A high-resolution crystal structure is reported for d(TpA)*, the intramolecular thymine-adenine photoadduct that is produced by direct ultraviolet excitation of the dinucleoside monophosphate d(TpA). It confirms the presence of a central 1,3-diazacyclooctatriene ring linking the remnants of the T and A bases, as previously deduced from heteronuclear NMR measurements by Zhao et al. (The structure of d(TpA)*, the major photoproduct of thymidylyl-(3'-5')-deoxyadenosine. Nucleic Acids Res., 1996, 24, 1554-1560). Within the crystal, the d(TpA)* molecules exist as zwitterions with a protonated amidine fragment of the eight-membered ring neutralizing the charge of the internucleotide phosphate monoanion. The absolute configuration at the original thymine C5 and C6 atoms is determined as 5S,6R. This is consistent with d(TpA)* arising by valence isomerization of a precursor cyclobutane photoproduct with cis-syn stereochemistry that is generated by [2 + 2] photoaddition of the thymine 5,6-double bond across the C6 and C5 positions of adenine. This mode of photoaddition should be favoured by the stacked conformation of adjacent T and A bases in B-form DNA. It is probable that the primary photoreaction is mechanistically analogous to pyrimidine dimerization despite having a much lower quantum yield.

Patient-Centered Care in Dermatologic Surgery: Practical Strategies to Improve the Patient Experience and Visit Satisfaction.

Patient-centered care in dermatologic surgery emphasizes addressing the preferences, values, and concerns of the surgical patient in an effort to improve the overall experience. Impediments affecting the delivery of Mohs micrographic surgical treatment of skin cancers are present throughout the perioperative period. Defining actionable strategies to improve outcomes can be challenging due to sparse literature and minimal high-quality scientific studies. This review focuses on the current evidence supporting practical recommendations in each surgical setting to improve the patient experience and increase visit satisfaction.

Evolution of Excisional Surgery Practices for Melanoma in the United States.

IMPORTANCE: National Comprehensive Cancer Network guidelines for melanoma have consistently recommended wide local excision as the standard of care since their inception. Although surgery with more comprehensive margin assessment (eg, Mohs surgery) has been advocated for certain subsets of melanoma, how often these techniques are used in clinical practice is uncertain. OBJECTIVE: To examine trends in the use of comprehensive margin assessment surgery for melanoma by tracking claims data for Mohs surgery. DESIGN, SETTING, AND PARTICIPANTS: This national cross-sectional analysis examined claims data from the Optum Clinformatics Data Mart, a nationally representative database. The study cohort consisted of 79 108 patients undergoing surgical excision for melanoma from January 1, 2001, through December 31, 2016. Data were analyzed from January 1, 2001, through December 31, 2016. MAIN OUTCOMES AND MEASURES: The primary outcome was the likelihood of a melanoma being treated with Mohs surgery over time, evaluated by multivariable logistic regression and expressed as the odds of treatment per additional calendar year. RESULTS: Among 79 108 patients with melanoma (median age, 63 years [interquartile range {IQR}, 51-73]; 47 407 men [59.9%]), 75 047 were treated with conventional excision (median age, 62 years [IQR, 50-73 years]; 44 786 men [59.7%]) and 4061 with Mohs surgery (median age, 67 years [IQR, 56-76 years]; 2621 men [64.5%]). Mohs surgery was used in 5.1% of all surgical cases, with the rate of Mohs surgery increasing 304% from 2.6% in 2001 to 7.9% in 2016. Odds of receiving Mohs surgery for melanoma increased significantly in more recent calendar years (odds ratio [OR], 1.02 per calendar year; 95% CI, 1.01-1.03; P < .001). Immunohistochemistry (IHC) use was only coded with Mohs surgery in 1087 cases (26.8%), and the odds of receiving Mohs surgery with IHC increased in more recent calendar years (OR, 1.13 per calendar year; 95% CI, 1.10-1.15; P < .001). Use of Mohs surgery and Mohs surgery with IHC for melanoma differed widely across geographic census divisions with greater than 3-fold variation between the regions with highest and lowest use in every period (eg, for 2013 through 2016, the East South Central region used Mohs surgery in 8.8% of melanoma excisions compared with 2.6 in the New England region). CONCLUSIONS AND RELEVANCE: Despite stable guidelines for melanoma surgery, the results of this study suggest that surgical practices for melanoma are evolving. Wide variations in surgical practice patterns for melanoma are present in the United States. This study's findings suggest that the effect of variations in surgical techniques on outcomes requires scrutiny and further study.