Periocular Mohs Reconstruction by Lateral Canthotomy With Inferior Cantholysis: A Retrospective Study.

BACKGROUND: Most eyelid defects after Mohs micrographic surgery are referred to oculoplastic surgery or plastic surgery for reconstruction, but growing evidence suggests the safety of such repairs performed by dermatologic surgeons is equivalent if not better. Lateral canthotomy with inferior cantholysis may be used by the dermatologic surgeon to reconstruct larger lower eyelid defects. OBJECTIVE: To demonstrate lateral canthotomy with inferior cantholysis performed by the dermatologic surgeon can result in safe, functionally and cosmetically acceptable surgical outcomes. MATERIALS AND METHODS: An institutional review board-approved retrospective study of repairs performed by a single dermatologic surgeon between January 2013 and August 2019. Patient demographics, operative and follow-up notes were reviewed. Two cosmetic dermatologists assessed aesthetic results based on final follow-up photographs using a visual analogue scale. RESULTS: Eight cases were included in the analysis. Seventy-five percent of patients were men, with a mean age of 74.1 years old. All tumors were basal cell carcinoma; the mean defect size was 2.4 cm2. No serious complications or postoperative interventions occurred. The median cosmetic score was 85.6 ± 11.5. CONCLUSION: Dermatologic surgeons can safely perform repairs of lower eyelid defects with lateral canthotomy with inferior cantholysis, achieving satisfactory functional and cosmetic outcomes.

Primary bilateral uveal melanoma: a population-based study and systematic review.

IMPORTANCE: Primary bilateral uveal melanoma (UM) is a rare and incompletely described entity. It is not known how these patients compare to those with unilateral UM. BACKGROUND: We sought to comprehensively characterize and compare patients with primary bilateral and unilateral UM. DESIGN: Retrospective, population-based and systematic review. PARTICIPANTS: Patients with bilateral (n = 52) and unilateral UM (n = 8915). METHODS: We analysed cases of primary bilateral UM from three data sources: (i) the University Hospitals Cleveland Medical Center pathology database from 1996 to 2016 (n = 1); (ii) the Surveillance, Epidemiology and End-Results (SEER)-18 database from 1973 to 2013 (n = 5) and (iii) a systematic review of the English language literature (n = 46). Cases of unilateral UM were obtained from the SEER-18 database from 1973 to 2013 for comparison (n = 8915). MAIN OUTCOME MEASURES: Demographics, clinicopathological characteristics, treatments and survival. RESULTS: There were no differences in sex, race, mean age at diagnosis, site of uveal involvement, metastases at diagnosis, or treatment among patients with bilateral as compared to unilateral UM. Additionally, there were no clinicopathological differences between the two UMs in each patient with bilateral disease. Overall survival did not differ between unilateral and bilateral UM patients, or between bilateral UM patients who presented with, or subsequently developed, bilateral disease. CONCLUSIONS AND RELEVANCE: Bilateral and unilateral UM patients share similar demographics, clinicopathological characteristics, treatments and prognoses. Moreover, the development of bilateral disease does not portend a poorer prognosis and patients should be treated similarly to those with unilateral disease.

ILK Index and Regrowth in Alopecia Areata.

There is insufficient data in the literature concerning optimal intralesional kenalog (ILK) dosing for the treatment of alopecia areata (AA). The purpose of this pilot study was to evaluate the utility of using the ratio of ILK received to initial Severity of Alopecia Tool (SALT) score to guide ILK dosing in patients with AA. Using photographic data from patients at baseline and 4-months follow-up, hair loss in 15 patients treated with AA was retrospectively graded using the SALT scores. The ILK received/initial SALT score (ILK index) was calculated for each patient, and the mean ILK index for patients who experienced significant (≥50%) and suboptimal (<50%) hair regrowth at 4 months follow-up were compared. Patients who experienced suboptimal hair regrowth had a lower ILK index on average than patients who experienced significant improvement. Although the difference did not meet significance (<0.1), the trend suggests that the ILK index, a novel calculation, may be a useful tool for guiding ILK dosing in the treatment of AA.

Differences in the demographics, incidence, and survival of palmar and plantar acral melanoma: a population-based study.

Acral melanoma (AM) has the worst prognosis of all cutaneous malignant melanomas (CMM). Differences between palmar and plantar tumors have not been well characterized at the population level. The objective of this study was to investigate the differences in demographics, incidence, and survival between palmar and plantar AM. The 2004-2016 National Cancer Database (NCDB) and 2000-2018 Surveillance, Epidemiology, and Results (SEER) databases were used to evaluate differences between palmar and plantar AM. Data were analyzed using Chi-square test, Fisher's exact, T-test, or likelihood ratio test. A total of 5002 participants were included in the study. A greater percentage of tumors occurred on the plantar surface (82.0%) than the palmar surface (18.0%). The incidence of plantar tumors is four times greater than palmar tumors (1.7 vs 0.4 cases per 1,000,000 people per year). Palmar melanomas were more likely to occur in Whites (84.6% vs 76.8%, p < 0.001) and be treated with amputation (28.1% vs 12.9%, p < 0.001) compared to plantar melanomas. Disease-specific five-year survival was similar for all palmar (80.8%) and plantar tumors (78.2%). While subtle differences do exist between palmar and plantar tumors, they behave similarly overall and should be treated as one entity.

Periosteal flaps allow for single stage reconstruction of larger full thickness eyelid defects: a retrospective study.

Full-thickness lower eyelid defects after Mohs micrographic surgery are frequently referred out to oculoplastic surgery for reconstruction. Reconstructive options include wedge closure with or without canthotomy/cantholysis and tarsoconjunctival sliding flaps. Defects > 50% of the eyelid margin have traditionally required the two-stage Hughes flap, leaving the patient with monocular vision for 3-6 weeks until pedicle division. To demonstrate single-stage periosteal flaps performed by dermatologic surgeons can result in safe, functional, and cosmetically acceptable repairs for large full thickness eyelid defects, an institutional review board-approved retrospective study of repairs performed by two dermatologic surgeons between January 2017 and July 2021 at the University of Minnesota. Patient demographics, operative notes, and follow-up notes were reviewed. Defect and follow-up photographs were scored using a visual analogue scale to assess aesthetic results. Ten cases were included in the analysis. Six patients were male and the average age was 62 years old. 8/10 were basal cell carcinoma and 2/10 were melanoma. The mean defect was 9.5 cm2, with a range of 1-24 cm2. The median cosmetic score was 85.8 ± 10.7. There were no serious complications reported. Mohs micrographic surgeons can safely and successfully reconstruct large, full thickness eyelid defects by periosteal flap.

Needs and Gaps in Resident Trainee Education, Clinical Patient Care, and Clinical Research in Cosmetic Dermatology: Position Statement of the Association of Academic Cosmetic Dermatology.

Cosmetic dermatology is a key subspecialty of academic dermatology. As such, academic centers are expected to demonstrate excellence in the teaching of cosmetic dermatology skills to trainees, the clinical delivery of cosmetic dermatology services to patients, and the performance of clinical research that advances knowledge and uncovers new therapies in cosmetic dermatology. The Association of Academic Cosmetic Dermatology (AACD), a newly formed medical professional society, includes as its principal aims the support of all of these areas. AACD is comprised of group of board-certified dermatologists who teach cosmetic and laser dermatology at US dermatology residency programs. An expert panel constituted by the AACD recently convened a workshop to review gaps pertaining to academic cosmetic dermatology. This panel considered needs and potential corrective initiatives in three domains: resident education, patient experience, and clinical research. The work of the panel was used to develop a roadmap, which was adopted by consensus, and which will serve to guide the AACD moving forward.

The Association of Academic Cosmetic Dermatology: improving cosmetic dermatology education through collaboration, research, and advocacy.

Cosmetic and laser procedures are increasingly popular among patients and are skills in which dermatologists are regarded as well trained. Most dermatology residents intend to incorporate cosmetic procedures into their practice and prefer to learn such procedures during residency through direct patient care. However, there are notable challenges in optimizing how residents are trained in cosmetic and laser dermatology. To address these barriers and elevate the practice of cosmetic dermatology in academic medicine, the Association of Academic Cosmetic Dermatology (AACD) was founded in 2021 as the lead professional society for dermatologists who direct the education of resident trainees in cosmetic and laser dermatology. The AACD, a group of board-certified dermatologists who teach cosmetic and laser dermatology to residents, aims to improve cosmetic dermatology education through collaboration, research, and advocacy.

Increased, but Functionally Impaired, CD14(+) HLA-DR(-/low) Myeloid-Derived Suppressor Cells in Psoriasis: A Mechanism of Dysregulated T Cells.

The clinical extent of psoriasis pathology is regulated in part by defects in immune networks, including a defect in the suppressive actions of regulatory T cells. Recently, CD14(+) HLA-DR(-/low) monocytic myeloid-derived suppressor cells (Mo-MDSCs) have been shown to suppress T-cell activation as one of their suppressive mechanisms. However, little is known about the role of Mo-MDSCs and their functional relationship to T-cell suppression in relation to human chronic immune-mediated inflammatory diseases, including psoriasis. Despite psoriasis being a hyperinflammatory condition, Mo-MDSCs were elevated in psoriatic patient peripheral blood mononuclear cells compared to nonpsoriatic healthy controls (2.6% vs. 0.9%, P < 0.002). Freshly isolated psoriatic Mo-MDSCs directly suppressed CD8 T-cell proliferation less efficiently than healthy control Mo-MDSCs. In addition, psoriatic Mo-MDSCs expressed reduced surface expression of programmed cell death protein 1 compared to healthy controls. Additional in vitro assays also demonstrated that psoriatic and control Mo-MDSCs both induce regulatory T-cell conversion from naïve T effector cells, but, importantly, the regulatory T cells induced by psoriatic Mo-MDSCs displayed decreased suppressive functionality. These results suggest that aberrations in psoriatic Mo-MDSCs prevent proper suppression of effector T-cell expansion and hamper the immune system's ability to correctly self-regulate.

Inhibition of recall responses through complementary therapies targeting CD8+ T-cell- and alloantibody-dependent allocytotoxicity in sensitized transplant recipients.

Allospecific T memory cell responses in transplant recipients arise from environmental exposure to previous transplantation or cross-reactive heterologous immunity. Unfortunately, these memory responses pose a significant barrier to the survival of transplanted tissue. We have previously reported that concurrent inhibition of CD154 and LFA-1 suppresses primary CD8-dependent rejection responses that are not controlled by conventional immunosuppressive strategies. We hypothesized that CD154- and LFA-1-mediated inhibition, by targeting activation as well as effector functions, may also be efficacious for the control of alloreactive CD8+ T-cell responses in sensitized hosts. We found that treatment with anti-LFA-1 mAb alone enhanced transplant survival and reduced CD8-mediated cytotoxicity in sensitized CD4 KO recipients. However, treatment with anti-CD154 mAb alone did not have an effect. Notably, when both CD4- and CD8-dependent rejection pathways are operative (wild-type sensitized recipients), LFA-1 significantly inhibited CD8-mediated in vivo allocytotoxicity but did not correspond with enhanced hepatocyte survival. We hypothesized that this was due to alloantibody-mediated rejection. When anti-LFA-1 mAb treatment was combined with macrophage depletion, which we have previously reported impairs alloantibody-mediated parenchymal cell damage, in vivo cytotoxic effector function was significantly decreased and was accompanied by significant enhancement of hepatocyte survival in sensitized wild-type recipients. Therefore, LFA-1 is a potent therapeutic target for reduction of CD8-mediated cytotoxicity in sensitized transplant recipients and can be combined with other treatments that target non-CD8-mediated recall alloimmunity.

Cytotoxic effector function of CD4-independent, CD8(+) T cells is mediated by TNF-α/TNFR.

BACKGROUND: Liver parenchymal cell allografts initiate both CD4-dependent and CD4-independent, CD8(+) T cell-mediated acute rejection pathways. The magnitude of allospecific CD8(+) T cell in vivo cytotoxic effector function is maximal when primed in the presence of CD4(+) T cells. The current studies were conducted to determine if and how CD4(+) T cells might influence cytotoxic effector mechanisms. METHODS: Mice were transplanted with allogeneic hepatocytes. In vivo cytotoxicity assays and various gene-deficient recipient mice and target cells were used to determine the development of Fas-, TNF-α-, and perforin-dependent cytotoxic effector mechanisms after transplantation. RESULTS: CD8(+) T cells maturing in CD4-sufficient hepatocyte recipients develop multiple (Fas-, TNF-α-, and perforin-mediated) cytotoxic mechanisms. However, CD8(+) T cells, maturing in the absence of CD4(+) T cells, mediate cytotoxicity and transplant rejection that is exclusively TNF-α/TNFR-dependent. To determine the kinetics of CD4-mediated help, CD4(+) T cells were adoptively transferred into CD4-deficient mice at various times posttransplant. The maximal influence of CD4(+) T cells on the magnitude of CD8-mediated in vivo allocytotoxicityf occurs within 48 hours. CONCLUSION: The implication of these studies is that interference of CD4(+) T cell function by disease or immunotherapy will have downstream consequences on both the magnitude of allocytotoxicity as well as the cytotoxic effector mechanisms used by allospecific CD8(+) cytolytic T cells.