Gram-negative anaerobes elicit a robust keratinocytes immune response with potential insights into HS pathogenesis.

Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS microbiome is polymicrobial with an abundance of commensal gram-positive facultative (GPs) Staphylococcus species and gram-negative anaerobic (GNA) bacteria like Prevotella, Fusobacterium and Porphyromonas with increasing predominance of GNAs with disease severity. We sought to define the keratinocyte response to bacteria commonly isolated from HS lesions to probe pathogenic relationships between HS and the microbiome. Type strains of Prevotella nigrescens, Prevotella melaninogenica, Prevotella intermedia, Prevotella asaccharolytica, Fusobacterium nucleatum, as well as Staphylococcus aureus and the normal skin commensal Staphylococcus epidermidis were heat-killed and co-incubated with normal human keratinocytes. RNA was collected and analysed using RNAseq and RT-qPCR. The supernatant was collected from cell culture for protein quantification. Transcriptomic profiles between HS clinical samples and stimulated keratinocytes were compared. Co-staining of patient HS frozen sections was used to localize bacteria in lesions. A mouse intradermal injection model was used to investigate early immune recruitment. TLR4 and JAK inhibitors were used to investigate mechanistic avenues of bacterial response inhibition. GNAs, especially F. nucleatum, stimulated vastly higher CXCL8, IL17C, CCL20, IL6, TNF and IL36γ transcription in normal skin keratinocytes than the GPs S. epidermidis and S. aureus. Using RNAseq, we found that F. nucleatum (and Prevotella) strongly induced the IL-17 pathway in keratinocytes and overlapped with transcriptome profiles of HS patient clinical samples. Bacteria were juxtaposed to activated keratinocytes in vivo, and F. nucleatum strongly recruited murine neutrophil and macrophage migration. Both the TLR4 and pan-JAK inhibitors reduced cytokine production. Detailed transcriptomic profiling of healthy skin keratinocytes exposed to GNAs prevalent in HS revealed a potent, extensive inflammatory response vastly stronger than GPs. GNAs stimulated HS-relevant genes, including many genes in the IL-17 response pathway, and were significantly associated with HS tissue transcriptomes. The close association of activated keratinocytes with bacteria in HS lesions and innate infiltration in murine skin cemented GNA pathogenic potential. These novel mechanistic insights could drive future targeted therapies.

Laser capture microdissection provides a novel molecular profile of human primary cutaneous melanoma.

Melanoma accounts for the majority of skin cancer-related mortality, highlighting the need to better understand melanoma initiation and progression. In-depth molecular analysis of neoplastic melanocytes in whole tissue biopsies may be diluted by inflammatory infiltration, which may obscure gene signatures specific to neoplastic cells. Thus, a method is needed to precisely uncover molecular changes specific to tumor cells from a limited sample of primary melanomas. Here, we performed laser capture microdissection (LCM) and gene expression profiling of patient-derived frozen sections of pigmented lesions and primary cutaneous melanoma. Compared to bulk tissue analysis, analysis of LCM-derived samples identified 9528 additional differentially expressed genes (DEGs) including melanocyte-specific genes like PMEL and TYR, with enriched of pathways related to cell proliferation. LCM methodology also identified potentially targetable kinases specific to melanoma cells that were not detected by bulk tissue analysis. Taken together, our data demonstrate that there are marked differences in gene expression profiles depending on the method of sample isolation. We found that LCM captured higher expression of melanoma-related genes while whole tissue biopsy identified a wider range of inflammatory markers. Taken together, our data demonstrate that LCM is a valid approach to identify melanoma-specific changes using a relatively small amount of primary patient-derived melanoma sample.

Hidradenitis suppurativa: new insights into disease mechanisms and an evolving treatment landscape.

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic disabling and debilitating inflammatory disease with a high unmet medical need. The prevalence of HS reported in most studies is 1-2%, although it is likely to be under-reported and estimates vary globally owing to variance in data collection methods, ethnicity, geographical location and under-diagnosis. HS is characterized by persistent, painful cutaneous nodules, abscesses and draining tunnels commonly affecting the axillary, anogenital, inguinal and perianal/gluteal areas. Over time, chronic uncontrolled inflammation results in irreversible tissue destruction and scarring. Although the pathophysiology of HS has not been fully elucidated, the tumour necrosis factor (TNF)-α and interleukin (IL)-17 pathways have an important role, involving multiple cytokines. Currently, treatment options include topical medications; systemic therapies, including repeated and/or rotational courses of systemic antibiotics, retinoids and hormonal therapies; and various surgical procedures. The anti-TNF-α antibody adalimumab is currently the only biologic approved by both the US Food and Drug Administration and the European Medicines Agency for HS; however, its efficacy varies, with a clinical response reported in approximately 50% of patients in phase III trials. HS is a rapidly evolving field of discovery, with a diverse range of agents with distinct mechanisms of action currently being explored in clinical trials. Several other promising therapeutic targets have recently emerged, and agents targeting the IL-17 and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways are the most advanced in ongoing or completed phase III clinical trials. Alongside limited therapeutic options, significant challenges remain in terms of diagnosis and disease management, with a need for better treatment outcomes. Other unmet needs include significant diagnostic delays, thus missing the therapeutic 'window of opportunity'; the lack of standardized outcome measures in clinical trials; and the lack of established, well-defined disease phenotypes and biomarkers.

Anatomic Location Influences Duration of Local Lidocaine Anesthesia in Dermatologic Surgery.

BACKGROUND: Although the onset and duration of local anesthetics are well-defined, how the anatomic site influences the duration of local anesthetics has not been well characterized in dermatology. OBJECTIVE: To define the duration of local anesthesia by anatomic site. MATERIALS AND METHODS: This was a prospective study. Adult healthy volunteers and patients undergoing Mohs micrographic surgery were invited to participate. The nose and the shin were chosen to represent highly and poorly vascularized anatomic sites, respectively. A total of 0.5 mL of buffered 1% lidocaine hydrochloride with 1:100,000 epinephrine was injected subcutaneously into each anatomic site of each participant. A pinprick test was used to assess adequate anesthesia until return of baseline sensation or visit completion. RESULTS: This study enrolled 25 participants. Time to return of sensation was significantly shorter on the nose compared with the shin ( p < .0001). On the nose, there was an association between male sex and shorter time to return of sensation. CONCLUSION: Time to return of sensation is significantly shorter on the nasal ala compared with the shin, suggesting that patients may regain sensation sooner on highly vascularized sites. Defining the duration of local anesthetics based on anatomic regions is important for treatment planning in dermatologic procedures.

Tape strips detect molecular alterations and cutaneous biomarkers in skin of patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) has a high unmet need for better treatments. Biopsies are considered the gold standard for studying molecular alterations in skin. A reproducible, minimally invasive approach is needed for longitudinal monitoring in trials and in pediatric populations. OBJECTIVE: To determine whether skin tape strips can detect molecular alterations in HS and identify biomarkers of disease activity. METHODS: We performed RNA sequencing on tape strips collected from lesional and healthy-appearing (nonlesional) HS skin (n = 22) and healthy controls (n = 21). We correlated the expression of skin biomarkers between tape strips and a previously published gene-signature of HS biopsies. RESULTS: Tape strips detected upregulation of known HS biomarkers (eg, Interleukin[IL]-17A) in nonlesional and/or lesional skin and also identified novel clinically actionable targets, including OX40 and JAK3. The expression of Th17 and tumor necrosis factor-α pathways were highly correlated between tape strips and biopsies. HS clinical severity was significantly associated with expression of biomarkers (eg tumor necrosis factor-α , IL-17 A/F, OX40, JAK1-3, IL-4R) in HS lesional and/or nonlesional skin. LIMITATIONS: Sample size. Tape stripping is limited in depth. CONCLUSION: This study validates tape strips as a minimally-invasive approach to identify cutaneous biomarkers in HS. This provides a novel avenue for monitoring treatment efficacy and a potential step toward individualized therapy in HS.

Ustekinumab reduces serum protein levels associated with cardiovascular risk in psoriasis vulgaris.

Psoriasis increases the risk of cardiovascular disease (CVD). Biomarkers for cardiovascular (CV) risk stratification in psoriasis are lacking, and the effects of psoriasis biologics on CV risk reduction remain unclear. The goal of this study was to identify biomarkers of CV risk in psoriasis blood that are reduced by ustekinumab. We quantified 276 inflammatory and CV-related serum proteins with Olink's multiplex assay in 10 psoriasis patients (vs. 18 healthy controls) and after 12 weeks of ustekinumab treatment. For each protein down-regulated after treatment, the literature was reviewed for studies assessing the protein's association with CVD. Data were collected from each study to calculate CV risk thresholds for each protein, which were compared with protein levels in psoriasis patients before and after treatment. Our results showed that 43 out of 276 proteins were down-regulated after treatment, 25 of which were initially up-regulated at baseline (vs. controls, all p-values ≤0.1). 8 down-regulated proteins were initially elevated above thresholds associated with enhanced CV risk in the literature (myeloperoxidase, C-X-C motif chemokine 10, E-selectin, interleukin-6, cystatin B, von Willebrand factor, tumor necrosis factor receptor 1 and N-terminal prohormone brain natriuretic peptide). Treatment lowered these proteins to below their risk thresholds, except for IL-6, which was lowered but remained at its risk threshold despite successful psoriasis skin treatment. In summary, 12 weeks of ustekinumab treatment reduced serum proteins present at levels associated with CV risk in psoriasis patients. Further studies can evaluate these proteins as potential ustekinumab-modulated biomarkers of CV risk in psoriasis and the impact of ustekinumab on CV risk reduction.

Interleukin-17RA blockade by brodalumab decreases inflammatory pathways in hidradenitis suppurativa skin and serum.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin disease with dysregulation of the interleukin (IL)-17 axis. Recently, we reported the clinical benefit of brodalumab, a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody, in moderate-to-severe HS. OBJECTIVES: To characterize the molecular response to brodalumab in HS skin and serum, and to identify biomarkers of treatment response. METHODS: Ten participants, who received brodalumab 210 mg /1·5 mL subcutaneously at weeks 0, 1, 2, 4 and every 2 weeks thereafter, were included in this molecular profiling study (NCT03960268). RNA sequencing and immunohistochemistry of nonlesional, perilesional and lesional HS skin biopsies, and Olink high-throughput proteomics of serum at baseline, weeks 4 and 12 were assessed. RESULTS: At week 12, brodalumab led to a decrease of overall inflammation, and improvement of psoriasis-, keratinocyte- and neutrophil-related pathways. Despite perilesional and lesional skin exhibiting no differentially expressed genes at baseline, treatment response was best assessed in perilesional skin. In serum, brodalumab treatment decreased pathways involved in neutrophil inflammation. Patients with higher baseline expression of neutrophil-associated lipocalin-2 (LCN2) in the skin or IL-17A in the serum demonstrated greater decreases of HS-related inflammatory cytokines as measured in skin biopsies at week 12. CONCLUSIONS: IL-17RA inhibition by brodalumab decreases several pathogenic inflammatory axes in HS. Perilesional skin provides a valid and robust assessment of treatment response. Expression of LCN2 in skin or IL-17A in serum may be used as biomarkers to stratify patients that may have a superior molecular response to brodalumab.

The inflammatory proteome of hidradenitis suppurativa skin is more expansive than that of psoriasis vulgaris.

BACKGROUND: Although hidradenitis suppurativa (HS) shares some transcriptomic and cellular infiltrate features with psoriasis, their skin proteome remains unknown. OBJECTIVE: To define and compare inflammatory protein biomarkers of HS and psoriasis skin. METHODS: We assessed 92 inflammatory biomarkers in HS (n = 13), psoriasis (n = 11), and control skin (n = 11) using Olink high-throughput proteomics. We also correlated HS skin and blood biomarkers using proteomics and RNA sequencing. RESULTS: We identified 57 differentially expressed proteins (DEPs) in lesional psoriasis and 64 DEPs in lesional HS skin, compared to healthy controls. Both HS and psoriasis lesional skin demonstrated a significant upregulation of T helper 1 and T helper 17 proteins. Healthy-appearing perilesional HS skin had 63 DEPs compared to healthy controls. Nonlesional HS and psoriasis skin had 24 and 7 DEPs, respectively, compared to healthy controls. Tumor necrosis factor and 8 other proteins were significantly correlated with clinical severity in perilesional HS skin (2 cm from a nodule). LIMITATIONS: Inclusion of only moderate-to-severe patients and the cohort size. CONCLUSION: HS has a greater inflammatory profile and is more diffusely distributed compared with psoriasis. Proteins correlated with disease severity are potential disease mediators. Perilesional skin is comparably inflamed to lesional skin, suggesting the need to treat beyond skin nodules.

High inflammation in hidradenitis suppurativa extends to perilesional skin and can be subdivided by lipocalin-2 expression.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease presenting with diverse manifestations ranging from nodules and abscesses to draining tunnels. Whether the underlying inflammation from lesions extends to relatively healthy-appearing adjacent perilesional and distant nonlesional skin has not been systematically evaluated. OBJECTIVE: We sought to characterize lesional, perilesional, and nonlesional skin in patients with HS. METHODS: Skin biopsy samples were collected under ultrasound guidance from patients with active, untreated moderate-to-severe HS. Site-matched control biopsy samples from healthy volunteers were used for comparison. RESULTS: RNA sequencing demonstrated that HS skin clustered separately from healthy control skin, with perilesional and lesion skin clustering together and away from nonlesional skin. Immunohistochemistry analysis identified psoriasiform hyperplasia with keratin 16 positivity in both perilesional and lesional skin, with comparable levels of CD3+, CD11c+, and neutrophil elastase-positive cellular infiltration. There was a marked upregulation of IL-17 signaling in perilesional and lesional skin. HS samples clustered on the basis of expression of lipocalin-2 (LCN2), with samples characterized by high LCN2 expression in the skin exhibiting a differing transcriptomic profile with significantly higher overall inflammation than that of skin characterized by low LCN2 levels. CONCLUSIONS: Perilesional HS skin has a transcriptomic and molecular profile comparable to that of lesional skin. HS can be grouped into 2 distinct subtypes based on molecular levels of LCN2 in the skin, with the LCN2-high subtype exhibiting an overall higher inflammatory burden and an upregulation of targetable cytokines. To our knowledge, this is the first study to characterize a unique HS subtype (and a potential endotype) that may guide future therapeutic targets.

Unna Boot With Keystone Advancement Flap Leads to Excellent Outcomes for Lower Extremity Reconstruction.

BACKGROUND: The reconstruction of lower extremity defects can be technically challenging. The keystone island perforator flap is a workhorse reconstructive option for difficult-to-repair regions, including the lower limb. The goal of this study is to evaluate outcomes using the keystone flap in combination with the zinc oxide compression dressing (Unna boot) for repair of lower extremity defects. METHODS: We retrospectively evaluated 96 patients who underwent resection of malignancies or atypical neoplasms on the lower legs. A total of 114 defects were repaired with the keystone flap in combination with the Unna boot. Post-operative outcomes were assessed. RESULTS: The combination of the keystone flap with postoperative Unna boot application led to excellent outcomes. There was no association between complication rates and patient co-morbidities. CONCLUSION: The combination of the keystone flap with the Unna boot is a safe and efficacious approach for reconstruction of lower extremity defects. J Drugs Dermatol. 2021;20(12):1308-1312. doi:10.36849/JDD.5915.

In-Depth Analysis of the Hidradenitis Suppurativa Serum Proteome Identifies Distinct Inflammatory Subtypes.

Hidradenitis suppurativa is a chronic inflammatory dermatosis with presentations ranging from painful nodules and abscesses to draining tunnels. Using an unbiased proteomics approach, we assessed cardiovascular-, cardiometabolic-, and inflammation-related biomarkers in the serum of patients with moderate-to-severe hidradenitis suppurativa. The serum of patients with hidradenitis suppurativa clustered separately from that of healthy controls and had an upregulation of neutrophil-related markers (Cathepsin D, IL-17A, CXCL1). Patients with histologically diagnosed dermal tunnels had higher serum lipocalin-2 levels compared with those without tunnels. Consistent with this, patients with tunnels had a more neutrophilic-rich serum signature, marked by Cathepsin D, IL-17A, and IL-17D alterations. There was a significant serum‒skin correlation between proteins in the serum and the corresponding mRNA expression in skin biopsies, with healthy-appearing perilesional skin demonstrating a significant correlation with neutrophil-related proteins in the serum. CSF3 mRNA levels in lesional skin significantly correlated with neutrophil-related proteins in the serum, suggesting that CFS3 in the skin may be a driver of neutrophilic inflammation. Clinical significantly correlated with the levels of lipocalin-2 and IL-17A in the serum. Using an unbiased, large-scale proteomic approach, we demonstrate that hidradenitis suppurativa is a systemic neutrophilic dermatosis, with a specific molecular signature associated with the presence of dermal tunnels.

Epithelialized tunnels are a source of inflammation in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic, painful, and burdensome inflammatory disease manifesting in nodules and abscesses, with progression to chronically draining tunnels in later-stage disease. OBJECTIVE: We sought to determine whether HS tunnels are immunologically active participants in disease activity. METHODS: Skin biopsy specimens were obtained by using ultrasound guidance in untreated patients with HS and those enrolled in an open-label study of brodalumab (ClinicalTrials.gov identifier NCT03960268) for patients with moderate-to-severe HS. RESULTS: Immunohistochemistry of HS biopsy specimens demonstrated that the epithelialized HS tunnels recapitulate the psoriasiform epidermal hyperplasia morphology of the overlying epidermis, displaying molecular inflammation, including S100A7 (psoriasin) positivity, as well as features of epidermal skin, including loricrin, filaggrin, lipocalin-2, and Melan-A positive cells. Tunnels were associated with increased infiltration of T cells, dendritic cells, and neutrophils; formation of neutrophil extracellular traps, and increased expression of psoriasiform proinflammatory cytokines. Unsupervised hierarchical clustering demonstrated a separation of HS samples based on the presence or absence of tunnels. Tunnels isolated by microdissection had higher levels of epithelium-derived inflammatory cytokines compared with the overlying epidermis and healthy controls. Clinically, the size and draining of the tunnels were decreased with treatment with the IL-17RA antagonist brodalumab. CONCLUSION: These data suggest that tunnels are a source of inflammation in HS.

Patient, Defect, and Surgical Factors Influencing Use of Ancillary Procedures after Facial Mohs Repairs.

This article determines if patient, defect, and repair factors can be used to predict the use of additional treatments to achieve optimal aesthetic results after repair of facial Mohs defects. An electronic chart review of patients undergoing Mohs excision and reconstruction of facial neoplasms from November 2005 to April 2017 was performed, reviewing patient demographics and history, tumor size, defect size and location, method and service of reconstruction, time between resection and repair, complications, and subsequent treatments. A total of 1,500 cases with basal cell and squamous cell carcinoma were analyzed. The average defect size was 3.09 ± 8.06 cm2; 81.9% of defects were less than 4 cm2 in size. Advancement flaps were used to repair 44.3% of defects. Complications and undesired sequelae (CUS) were noted in 15.9% of cases; scar hypertrophy or keloid (10.8%) was most common. Postoperative ancillary procedures were performed in less than one-quarter (23.4%) of patients to enhance the postrepair appearance; the most common procedures were intralesional corticosteroid injections and pulse dye laser treatments. CUS were more likely in females (19.6%), defects on the lips (28.7%) and on the nose (27.3%) (p < 0.001 for each). Females (22.7% vs. 12.7%), lip repairs (40.2% vs. 18.3%), transposition flaps (39.2% vs. 14.8%), and repairs performed by a dermatologist (17.9% vs. 11.2%) (p < 0.001 for each) were more likely to be treated with postoperative corticosteroid injections. Females (14.5% vs. 7.4%), patients under the age of 60 years (13.9% vs. 8.8%), and patients whose repair was performed by a dermatologist (11.9% vs. 2.9%) (p < 0.001 for each) were more likely to receive postoperative pulsed dye laser treatments. CUS and ancillary procedures after repair of facial Mohs defects are uncommon. Awareness of individual risk factors and defect characteristics allows the surgeon to choose the most appropriate repair technique while anticipating the potential need for ancillary procedures.

Ipilimumab plus nivolumab for patients with metastatic uveal melanoma: a multicenter, retrospective study.

BACKGROUND: Uveal melanoma (UM) is the most common intraocular malignancy in adults. In contrast to cutaneous melanoma (CM), there is no standard therapy, and the efficacy and safety of dual checkpoint blockade with nivolumab and ipilimumab is not well defined. METHODS: We conducted a retrospective analysis of patients with metastatic UM (mUM) who received treatment with ipilimumab plus nivolumab across 14 academic medical centers. Toxicity was graded using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methodology. RESULTS: 89 eligible patients were identified. 45% had received prior therapy, which included liver directed therapy (29%), immunotherapy (21%), targeted therapy (10%) and radiation (16%). Patients received a median 3 cycles of ipilimumab plus nivolumab. The median follow-up time was 9.2 months. Overall response rate was 11.6%. One patient achieved complete response (1%), 9 patients had partial response (10%), 21 patients had stable disease (24%) and 55 patients had progressive disease (62%). Median OS from treatment initiation was 15 months and median PFS was 2.7 months. Overall, 82 (92%) of patients discontinued treatment, 34 due to toxicity and 27 due to progressive disease. Common immune-related adverse events were colitis/diarrhea (32%), fatigue (23%), rash (21%) and transaminitis (21%). CONCLUSIONS: Dual checkpoint inhibition yielded higher response rates than previous reports of single-agent immunotherapy in patients with mUM, but the efficacy is lower than in metastatic CM. The median OS of 15 months suggests that the rate of clinical benefit may be larger than the modest response rate.

The Effects of Primary Defect Characteristics on Reconstruction Type and Adjunctive Intervention in Mohs Micrographic Surgery: A Retrospective Review.

BACKGROUND: Cosmetic concerns following Mohs Micrographic surgery (MMS) are significant and may require adjunctive treatments for unsatisfactory appearance. OBJECTIVE: To determine factors associated with adjunctive cosmetic intervention for facial defects following MMS. METHODS AND MATERIALS: A retrospective review of 699 patients undergoing repair of facial defects after MMS from 2008-2018 was performed. Tumor types, defect sizes, patient demographics, repair methods, complications, and post-operative cosmetic interventions were examined. RESULTS: 666 Mohs cases and resultant defects were analyzed. The most common method of repair following MMS was primary closure (52.3%), and the most common post-operative intervention was steroid injection (18.3%). The lip subunit was more than twice as likely as other locations to be treated with steroid injections (P<.001). The lip subunit also had the highest frequency of scar revision (13%; P<0.001). Patients who had primary closure were less likely to require scar revision (P=0.003) or dermabrasion (P=0.042), and there was no significant association between skin graft repair and cosmetic intervention. CONCLUSIONS: Both defect subunit and closure type were independently associated with adjunctive cosmetic intervention following MMS. Defect size was not significantly associated with an adjunctive intervention in our study. Understanding the factors affecting the need for adjunctive cosmetic interventions may improve patient counseling prior to Mohs repair. J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.4701.

The effect of subcutaneous brodalumab on clinical disease activity in hidradenitis suppurativa: An open-label cohort study.

BACKGROUND: Hidradenitis suppurativa is an autoinflammatory disorder of keratinization, with dysregulation of T helper type 17 cytokines. Brodalumab is a monoclonal antibody that targets the interleukin (IL) 17 receptor A receptor. OBJECTIVES: To assess the safety and tolerability and clinical response at weeks 12 and 24 of brodalumab in moderate to severe HS. Ten participants with no history of inflammatory bowel disease were administered brodalumab 210 mg/1.5 mL subcutaneously at weeks 0, 1, and 2 and every 2 weeks thereafter until week 24. Participants were assessed for adverse events (grade 2/3 adverse events) and clinical response (Hidradenitis Suppurativa Clinical Response [HiSCR], Sartorius, International Hidradenitis Suppurativa Severity Scoring System [IHS4]), including ultrasonography and skin biopsies. RESULTS: All 10 participants completed the study. No grade 2/3 adverse events associated with the use of brodalumab were reported. All patients (100%) achieved HiSCR, and 80% achieved IHS4 category change at week 12. HiSCR achievement occurred as early as week 2, likely due to the unique blockade of IL-17A, IL-17C, and IL-17F by brodalumab. Significant improvements were seen in pain, itch, quality of life, and depression. CONCLUSIONS: Brodalumab was well tolerated in this HS cohort, with no serious adverse events and improvement in clinical outcomes. Alterations in dose frequency may be required in those with advanced disease, which requires further exploration.

V-Y Hemi-keystone Advancement Flap: A Novel and Simplified Reconstructive Modification.

BACKGROUND: The keystone perforator flap design has been gaining popularity for reconstruction of cutaneous defects due to its robust vascular supply and high rates of flap survival. However, the design requires significant tissue mobilization relative to the defect and is consequently technically demanding, time intensive, and has associated morbidity. We present a novel, simplified modification of the keystone flap that may increase its reconstructive applications. METHODS: A retrospective chart review was conducted of patients who underwent V-Y hemi-keystone advancement flap reconstruction of cutaneous defects by a single surgeon. Outcomes of interest included wound healing complications. RESULTS: Eighty-six consecutive V-Y hemi-keystone advancement flaps were performed with an overall complication rate of 7% (6/86). Reconstruction sites included lower extremities (75/86, 87.2%), upper extremities (9/86, 10.5%), and the trunk (2/86, 2.3%). Mean follow-up time was 26.3 weeks. Four out of 5 surgical site infections occurred on lower extremity wounds. There were no cases of complete or partial flap loss. CONCLUSIONS: The current series presents a simplification of the traditional keystone flap that decreases surgical complexity and time required for successful reconstruction of cutaneous defects, especially in challenging wounds on the lower extremities. The complication rates were similar, or lower, than previously reported series of keystone flap reconstructions. The consistently favorable outcome of this technique supports the integration of the V-Y hemi-keystone advancement flap into reconstructive surgery.