Treatment of Angiosarcoma of the Head and Neck: A Systematic Review.

Primary cutaneous angiosarcoma (cAS) of the head and neck is a rare sarcoma with a poor prognosis and limited treatment options. We conducted a systematic review of treatments used for head and neck cAS and determined the treatment modalities that offer the longest mean overall survival (OS). Forty publications totaling 1295 patients were included. Both surgical and nonsurgical modalities have shown potential efficacy in the treatment of cAS; however, limited data preclude definitive recommendations. Multidisciplinary management of cAS should be considered to tailor treatment on a case-by-case basis.

Development of an international glossary for clinical guidelines collaboration.

OBJECTIVES: Clinical practice guidelines (CPGs) are often created through collaboration among organizations. The use of inconsistent terminology may cause poor communication and delays. This study aimed to develop a glossary of terms related to collaboration in guideline development. STUDY DESIGN AND SETTING: A literature review of collaborative guidelines was performed to develop an initial list of terms related to guideline collaboration. The list of terms was presented to the members of the Guideline International Network Guidelines Collaboration Working Group, who provided presumptive definitions for each term and proposed additional terms to be included. The revised list was subsequently reviewed by an international, multidisciplinary panel of expert stakeholders. Recommendations received during this pre-Delphi review were implemented to augment an initial draft glossary. The glossary was then critically evaluated and refined through two rounds of Delphi surveys and a virtual consensus meeting with all panel members as Delphi participants. RESULTS: Forty-nine experts participated in the pre-Delphi survey, and 44 participated in the two-round Delphi process. Consensus was reached for 37 terms and definitions. CONCLUSION: Uptake and utilization of this guideline collaboration glossary by key organizations and stakeholder groups may facilitate collaboration among guideline-producing organizations by improving communication, minimizing conflicts, and increasing guideline development efficiency.

Treatment of traumatic hypertrophic scars and keloids: a systematic review of randomized control trials.

Exaggerated healing and remodeling after skin injury may cause hypertrophic and keloidal scars, which are associated with functional and quality of life impairment. There is limited guidance available regarding the relative effectiveness of therapies for hypertrophic scars and keloids. In this review, we aim to compare the effectiveness of treatments for hypertrophic scars and keloids. MEDLINE, Embase, Scopus, and the Cochrane Collaboration database were searched from inception to March 2019 for randomized control trials of treatments for hypertrophic and keloid scars that included 20 or more patients. Outcomes evaluated included the standardized mean reduction in scarring and adverse events. The type of scar and the demographic features were analyzed for their effect on clinical outcome. Based on 25 included clinical trials, intralesional injection (64.1% [95% CI 60.8-67.5%]) may be more effective than physical (29.9% [95% CI 28.9-30.9%]) or topical treatments (34% [95% CI 31.8-36.8%]). Combination of 5-fluorouracil and triamcinolone (9:1 dilution) appeared superior among intralesional treatments for keloids. Ablative laser and pulsed-dye laser were the most useful laser treatments. Regression modeling showed laser treatment response was linked to Fitzpatrick skin type (p = 0.002). Adverse events were uncommon for all treatments and mostly transient. Intralesional treatments for keloid and hypertrophic scars may be the most reliable treatment option to improve pathologic scars, while laser treatment may have specific benefits for Fitzpatrick skin types I-III over types IV-VI. Management of pathological scars is an area of critical need, where appropriate treatment can have a significant impact on quality of life.

Dermatopathologic features of cutaneous squamous cell carcinoma and actinic keratosis: Consensus criteria and proposed reporting guidelines.

BACKGROUND: There is considerable variation in the literature regarding the dermatopathologic diagnostic features of and reporting guidelines for actinic keratosis (AK) and cutaneous squamous cell carcinoma (cSCC). OBJECTIVE: To develop consensus recommendations regarding diagnostic criteria, nomenclature, and reporting of AK and cSCC. METHODS: Literature review and cross-sectional multiround Delphi process including an international group of expert dermatopathologists followed by a consensus meeting. RESULTS: Consensus was achieved regarding the key dermatopathologic features necessary for diagnosing cSCC, AK, and associated variants; grading of degree of cellular differentiation in cSCC; utility of immunohistochemistry for diagnosis of cSCC; and pathologic features that should be reported for cSCC and AK. LIMITATIONS: Consensus was not achieved on all questions considered. CONCLUSION: Despite the lack of clarity in the literature, there is consensus among expert dermatopathologists regarding diagnostic criteria and appropriate reporting of AK and cSCC. Widespread implementation of these consensus recommendations may improve communication between dermatopathologists and clinicians, facilitating appropriate treatment of AK and cSCC.

Improvements and advances in core outcome set methodology: proceedings of the CS-COUSIN & COMFA Joint Meeting.

A COS is a systematically developed list of outcomes recommended for reporting all studies within a particular disease area. The Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) and the Core Outcome Measures in Food Allergy (COMFA) Initiative Joint Meeting was held virtually on September 23 through 28, 2021. This meeting brought together core outcome set (COS) developers within the domains of dermatology and food allergy, respectively. The meeting assessed the state of COS methodology, provided a forward look, and facilitated the networking of members of individual COS groups. The meeting hosted several expert-led key addresses and focus sessions, in which work was critically discussed, new developments were shared, and groundwork was laid for future projects. The conference emphasized the importance of ongoing COS work to improve patient outcomes and limit research waste.

Evidence-Based Clinical Practice Guidelines for Laser-Assisted Drug Delivery.

Importance: Laser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD. Objective: To develop recommendations for the safe and effective use of LADD. Evidence Review: A systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved. Findings: Of the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline's 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections. Conclusions and Relevance: This systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique.

Voting behavior during FDA Medical Device Advisory Committee panel meetings.

OBJECTIVES: During premarket review, the US Food and Drug Administration may ask its Medical Device Advisory Committee (MDAC) Panels to assess the safety and effectiveness of medical devices being considered for approval. The objective of this study is to assess the relationship, if any, between individual votes and Panel recommendations and: (1) the composition of Panels, specifically the expertise and demographic features of individual members; or (2) Panel members' propensity to speak during Panel deliberations. METHODS: This was a retrospective cohort study of routinely collected data from voting members of MDAC panels convened between January 2011 to June 2016 to consider premarket approval. Data sources were verbatim transcripts available publicly from the FDA. Number of words spoken, directionality of votes on device approval, profession, and demographics were collected. RESULTS: 658,954 words spoken by 536 members during 49 meetings of 11 Panels were analyzed. Based on multivariate analysis, biostatisticians spoke more (+373 words; P = 0.0002), and women (-187 words; P = 0.0184) and other non-physician voting members less (-213 words; P = 0.0306), than physicians. Speaking more was associated with abstaining (P = 0.0179), and with voting against the majority (P = 0.0153). Non-physician, non-biostatistician members (P = 0.0109), and those having attended more meetings as a voting member (P = 0.0249) were more likely to vote against approval. In bivariable analysis, unanimous Panels had a greater proportion of biostatisticians (mean 0.1580; 95% CI 0.1237-0.1923) than non-unanimous Panels (0.1107; 95% CI 0.0912-0.1301; p = 0.0201). CONCLUSIONS: Panelists likely to vote against the majority include non-physician, non-biostatisticians; experienced Panelists; and more talkative members. The increased presence of biostatisticians on Panels leads to greater voting consensus. Having a diversity of opinions on Panels, including in sufficient numbers those members likely to dissent from majority views, may help ensure that a diversity of opinions are aired before decision-making.

Spaceflight Analogue Culture Enhances the Host-Pathogen Interaction Between Salmonella and a 3-D Biomimetic Intestinal Co-Culture Model.

Physical forces associated with spaceflight and spaceflight analogue culture regulate a wide range of physiological responses by both bacterial and mammalian cells that can impact infection. However, our mechanistic understanding of how these environments regulate host-pathogen interactions in humans is poorly understood. Using a spaceflight analogue low fluid shear culture system, we investigated the effect of Low Shear Modeled Microgravity (LSMMG) culture on the colonization of Salmonella Typhimurium in a 3-D biomimetic model of human colonic epithelium containing macrophages. RNA-seq profiling of stationary phase wild type and Δhfq mutant bacteria alone indicated that LSMMG culture induced global changes in gene expression in both strains and that the RNA binding protein Hfq played a significant role in regulating the transcriptional response of the pathogen to LSMMG culture. However, a core set of genes important for adhesion, invasion, and motility were commonly induced in both strains. LSMMG culture enhanced the colonization (adherence, invasion and intracellular survival) of Salmonella in this advanced model of intestinal epithelium using a mechanism that was independent of Hfq. Although S. Typhimurium Δhfq mutants are normally defective for invasion when grown as conventional shaking cultures, LSMMG conditions unexpectedly enabled high levels of colonization by an isogenic Δhfq mutant. In response to infection with either the wild type or mutant, host cells upregulated transcripts involved in inflammation, tissue remodeling, and wound healing during intracellular survival. Interestingly, infection by the Δhfq mutant led to fewer transcriptional differences between LSMMG- and control-infected host cells relative to infection with the wild type strain. This is the first study to investigate the effect of LSMMG culture on the interaction between S. Typhimurium and a 3-D model of human intestinal tissue. These findings advance our understanding of how physical forces can impact the early stages of human enteric salmonellosis.

Nonmelanoma Skin Cancer in Patients Older Than Age 85 Years Presenting for Mohs Surgery: A Prospective, Multicenter Cohort Study.

Importance: It has been suggested that Mohs surgery for skin cancer among individuals with limited life expectancy may be associated with needless risk and discomfort, along with increased health care costs. Objective: To investigate patient- and tumor-specific indications considered by clinicians for treatment of nonmelanoma skin cancer in older individuals. Design, Setting, and Participants: This multicenter, prospective cohort study was conducted using data from US private practice and academic centers. Included patients were those older than age 85 years presenting for skin cancer surgery and referred for Mohs surgery, with reference groups of those younger than age 85 years receiving Mohs surgery and those older than age 85 years not receiving Mohs surgery. Data were analyzed from November 2018 through January 2019. Exposures: Mohs surgery for nonmelanoma skin cancer. Main Outcomes and Measures: Reason for treatment selection. Results: Among 1181 patients older than age 85 years referred for Mohs surgery (724 [61.9%] men among 1169 patients with sex data; 681 individuals aged >85 to 88 years [57.9%] among 1176 patients with age data) treated at 22 sites, 1078 patients (91.3%) were treated by Mohs surgery, and 103 patients (8.7%) received alternate treatment. Patients receiving Mohs surgery were more likely to have tumors on the face (738 patients [68.5%] vs 26 patients [25.2%]; P < .001) and nearly 4-fold more likely to have high functional status (614 patients [57.0%] vs 16 patients [15.5%]; P < .001). Of 15 distinct reasons provided by surgeons for opting to proceed with Mohs surgery, the most common were patient desire for treatment with a high cure rate (712 patients [66.0%]), good or excellent patient functional status for age (614 patients [57.0%]), and high risk associated with the tumor based on histology (433 patients [40.2%]). Conclusions and Relevance: This study found that older patients who received Mohs surgery often had high functional status, high-risk tumors, and tumors located on the face. These findings suggest that timely surgical treatment may be appropriate in older patients given that their tumors may be aggressive, painful, disfiguring, and anxiety provoking.

Protocol for development of a core outcome set for clinical trials in melasma.

INTRODUCTION: Melasma is a pigmentation disorder of the skin. Characterised by brown to gray-brown patches on the face and neck, the condition predominantly affects women and has been associated with pregnancy, hormonal variation and sun exposure. Melasma can be disfiguring and anxiety-provoking, and quality of life is often adversely impacted. Management includes sun protection, laser and energy device therapy, topical and oral skin-bleaching agents and chemical peels. While clinical trials of melasma exist, there is a lack of consistency in reported outcomes, which has been a barrier to the aggregation of data in systematic reviews and meta-analyses. This protocol describes a planned process for development of a minimum set of outcomes (ie, 'core outcome set') that should be measured in all clinical trials of melasma. METHODS AND ANALYSIS: An exhaustive list of potential outcomes will be extracted from four sources: (1) systematic literature review of outcomes in clinical trials; (2) semistructured patient interviews; (3) brochures, pamphlets, clinical trial registries, and other published and unpublished sources and documentation; and (4) interviews with non-patient, non-physician stakeholders, including federal regulators, industry scientists and non-physician providers. An international two-round Delphi process will then be performed to identify the outcomes deemed most important to patients and physicians. Subsequently, a consensus meeting will be convened to review and process the results, and to vote on a final set of core outcomes. ETHICS AND DISSEMINATION: Ethics approval was provided by the Northwestern University Institutional Review Board (protocol ID: STU00201637). This study is registered with both the Core Outcome Measures in Effectiveness Trials and Cochrane Skin-Core Outcome Set Initiative initiatives, and this protocol is in accordance with the guidelines for protocol development of both groups. All findings from the study described in this protocol will be disseminated to all stakeholders involved in the development process and will be submitted for publication in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020214189.

Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease.

IMPORTANCE: Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms. OBJECTIVE: To develop recommendations for the care of adults with EMPD. EVIDENCE REVIEW: A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD. FINDINGS: The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years. CONCLUSIONS AND RELEVANCE: Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.