European e-Delphi process to define expert consensus on electrochemotherapy treatment indications, procedural aspects, and quality indicators in melanoma.

BACKGROUND: Skin metastases are an important co-morbidity in melanoma. Despite broad adoption, electrochemotherapy implementation is hindered by a lack of treatment indications, uncertainty regarding procedural aspects, and the absence of quality indicators. An expert consensus may harmonize the approach among centres and facilitate comparison with other therapies. METHODS: An interdisciplinary panel was recruited for a three-round e-Delphi survey. A literature-based 113-item questionnaire was proposed to 160 professionals from 53 European centres. Participants rated each item for relevance and degree of agreement on a five-point Likert scale, and received anonymous controlled feedback to allow revision. The items that reached concordant agreement in two successive iterations were included in the final consensus list. In the third round, quality indicator benchmarks were defined using a real-time Delphi method. RESULTS: The initial working group included 122 respondents, of whom 100 (82 per cent) completed the first round, thus qualifying for inclusion in the expert panel (49 surgeons, 29 dermatologists, 15 medical oncologists, three radiotherapists, two nurse specialists, two clinician scientists). The completion rate was 97 per cent (97 of 100) and 93 per cent (90 of 97) in the second and third rounds respectively. The final consensus list included 54 statements with benchmarks (treatment indications, (37); procedural aspects, (1); quality indicators, (16)). CONCLUSION: An expert panel achieved consensus on the use of electrochemotherapy in melanoma, with a core set of statements providing general direction to electrochemotherapy users to refine indications, align clinical practices, and promote quality assurance programmes and local audits. The residual controversial topics set future research priorities to improve patient care.

Electrochemotherapy is an effective locoregional therapy for skin metastases from melanoma, a problem faced by almost half of patients with metastatic disease. The lack of comparative studies and the heterogeneity of its clinical application among centres make it challenging to support consistent, evidence-based recommendations. To address this unmet need, a three-round online survey was conducted to establish a consensus on treatment indications, standard operating procedures, and quality indicators. In the survey, a panel of 100 European melanoma experts agreed on 56 statements that can be used to improve patient selection, homogenize treatment application, and monitor outcomes.

[Psychiatric comorbidities in hidradenitis suppurativa/acne inversa]. / Psychiatrische Komorbidität bei Hidradenitis suppurativa/Acne inversa.

BACKGROUND: The findings of most studies suggest that depression and anxiety disorders are the most common psychiatric comorbidities in patients with hidradenitis suppurativa/acne inversa (HS/AI). METHODS: In a prospective study, 51 patients with HS/AI were further examined for psychiatric comorbidity using a standardized interview and questionnaires. RESULTS: In psychiatric examination, 29.4% of HS/AI patients had additional mental symptoms, mainly manifested as depressive disorder. The HS/AI patients were rather young and female, and they showed a high incidence of nicotine and alcohol use, and a positive family history of paternal alcohol dependence. In addition, HS/AI patients experienced more severe psychosocial impairments in the form of lack of partnership and lower school attainment. CONCLUSIONS: Acne inversa is a severe chronic inflammatory skin disease that, like other inflammatory dermatoses, is associated with mental comorbidity and psychosocial impairments. Since especially young patients are affected, a psychiatric-psychotherapeutic cotreatment should be considered already at an early stage.

Wound Care With a Porcine Extracellular Matrix After Surgical Treatment of Rhinophyma.

BACKGROUND: Rhinophyma surgery is commonly associated with prolonged wound healing and the need for multiple wound dressings. OBJECTIVES: To evaluate clinical outcome with a porcine extracellular matrix (ECM) after shave excision of rhinophyma compared with common wound care procedure. MATERIALS AND METHODS: Retrospective analysis of patients with common dressings (CD) compared with patients with additional ECM (OASIS) application. Clinical findings were assessed prior to treatment and at follow-up visit using the Patient and Observer Scar Assessment Scale (POSAS), Vancouver Scar Scale (VSS), and Rhinophyma Severity Index (RHISI). RESULTS: Overall, 28 patients (67.5 ±9.0 years) with a mean wound area of 33.9 (±8.5) cm² were included. After a mean follow-up period of 132 (±73) days, scales of POSAS, VSS, and RHISI showed significant (P< .0001) reductions of 47.0% (±11.1), 56.0% (±12.0), and 62.3% (±14.3), respectively. Subgroup analysis showed no significant differences of aforementioned parameters between the ECM group (n= 17) and CD group (n= 11). In contrast, the number of dressing changes were significantly (P< .006) less in the ECM group (1.4 ±0.8) compared with CD group (4.1 ±2.6). The ECM group showed a significant (P< .017) shorter time to re-epithelization (10.5 ±1.7 days) than the CD group (13.1 ±2.2 days). CONCLUSIONS: The application of porcine ECM is practicable and reduces the number of dressing changes and time to re-epithelization clearly. Crusts are scaling off spontaneously without any aggressive action needed. Our findings indicate that ECM application is a promising approach for rhinophyma wound care.

Dicer Sequencing, Whole Genome Methylation Profiling, mRNA and smallRNA Sequencing Analysis in Basal Cell Carcinoma.

BACKGROUND/AIMS: Perturbations in the expression of microRNAs (miRNAs) and their maturing machinery components such as Dicer have been previously described for basal cell carcinoma (BCC). However, the mutational status of Dicer in BCC is unclear. Further, the sclerodermiform subtype of BCC (sBCC) has not been previously investigated regarding its methylation profile or its smallRNA expression profile via RNA sequencing. We conducted this study to investigate the mutational status of Dicer in BCC. METHODS: Dicer sequencing was performed on the Illumina MiSeq System in a total of 16 BCC samples (8 nodular BCCs, 8 sBCCs) and mapped against the human reference genome (i.e., hg19). Dicer sequencing was performed in all 16 BCC samples. We performed whole genome methylation profiling with Infinium MethylationEPIC BeadChips as well as mRNA and smallRNA sequencing in 5 sBCCs with the Illumina NextSeq500 next-generation sequencing system. RESULTS: Compared to the wildtype Dicer sequence, we found 5 to 7 variants per sBCC sample including insertion, deletion, and multiple nucleotide variants. Global methylation profiles were highly similar between groups. mRNA sequencing revealed S100A9, KRT14, KRT10, S100A8, S100A7, COX1, KRT1, COX3, and smallRNA sequencing analysis miR-21, miR-99a, miR26-a-2, let-7f, let-7g, let-7i, miR-100, and miR-205 were the most strongly expressed in sBCCs. CONCLUSION: We identified a variety of Dicer mutations that could play a role in aberrant miRNA expression in BCC. The noted RNA sequences should be further evaluated in functional studies to explore their potential pathogenetic role in sBCC.

Altered Global 5-Hydroxymethylation Status in Hidradenitis Suppurativa: Support for an Epigenetic Background.

BACKGROUND: The pathogenesis of hidradenitis suppurativa (HS), with its complex inflammatory network, is still elusive. Imbalances in DNA methylation can lead to genome destabilization and have been assumed to play a role in inflammatory diseases. Global DNA methylation and hydroxymethylation have not been studied in HS yet. OBJECTIVE: We conducted this study to investigate the global DNA methylation and hydroxymethylation status in lesional and perilesional HS skin compared to healthy controls. METHODS: Immunohistochemical analysis was performed for 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in 30 lesional and 30 corresponding healthy-appearing perilesional HS tissue samples. We included 30 healthy subjects as an interindividual control group. RESULTS: 5-hmC levels were significantly lower in healthy-appearing perilesional (p < 0.0001) and lesional HS skin (p < 0.0001) when compared to healthy controls. There was no significant difference between lesional HS skin and perilesional HS skin regarding 5-hmC levels (p = 0.6654). In contrast to 5-hmC, 5-mC staining showed no significant changes between the 3 groups. Univariate analysis revealed no significant association between patients' characteristics, disease severity, and the levels of 5-mC and 5-hmC. CONCLUSION: Our findings indicate that imbalances in DNA hydroxymethylation may play a role in the pathogenesis of HS rather than DNA methylation. Further studies are warranted to investigate the significance of DNA hydroxymethylation and the regulating enzymes in HS in order to advance our knowledge of the inflammatory network in this disease.

Long-noncoding RNAs in basal cell carcinoma.

Long noncoding RNAs (lncRNAs) are fundamental regulators of pre- and post-transcriptional gene regulation. Over 35,000 different lncRNAs have been described with some of them being involved in cancer formation. The present study was initiated to describe differentially expressed lncRNAs in basal cell carcinoma (BCC). Patients with BCC (n = 6) were included in this study. Punch biopsies were harvested from the tumor center and nonlesional epidermal skin (NLES, control, n = 6). Microarray-based lncRNA and mRNA expression profiles were identified through screening for 30,586 lncRNAs and 26,109 protein-coding transcripts (mRNAs). The microarray data were validated by RT-PCR in a second set of BCC versus control samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of mRNAs were performed to assess biologically relevant pathways. A total of 1851 lncRNAs were identified as being significantly up-regulated, whereas 2165 lncRNAs were identified as being significantly down-regulated compared to nonlesional skin (p < 0.05). Oncogenic and/or epidermis-specific lncRNAs, such as CASC15 or ANRIL, were among the differentially expressed sequences. GO analysis showed that the highest enriched GO targeted by up-regulated transcripts was "extracellular matrix." KEGG pathway analysis showed the highest enrichment scores in "Focal adhesion." BCC showed a significantly altered lncRNA and mRNA expression profile. Dysregulation of previously described lncRNAs may play a role in the molecular pathogenesis of BCC and should be subject of further analysis.

Microbial Profile and Antimicrobial Susceptibility of Bacteria Found in Inflammatory Hidradenitis Suppurativa Lesions.

BACKGROUND: The role of bacterial colonization in hidradenitis suppurativa (HS) lesions is poorly understood. To date, data on the related microbial profile and especially on bacterial resistance rates are scarce. METHODS: The results of bacterial cultures and susceptibility patterns of the isolated microorganisms obtained from deep portions of HS lesions from patients who underwent surgery at our HS Centre between 2010 and 2015 were retrospectively evaluated. RESULTS: Analyses of 113 bacterial samples from 113 HS patients revealed bacterial growth in 95 samples (84.1%). Polymicrobial growth was found in 51 samples (45.1%). Coagulase-negative staphylococci and Staphylococcus aureus were the most commonly isolated bacteria, followed by Proteus mirabilis and Escherichia coli. Data on susceptibility testing were available for 68 samples, which yielded 129 isolates. The isolated strains were primarily resistant to penicillin G, followed by erythromycin, clindamycin and ampicillin. The highest effectiveness against isolates was observed for fosfomycin, imipenem, fluoroquinolones (moxifloxacin, ciprofloxacin, levofloxacin), and cotrimoxazole. CONCLUSIONS: Our findings on bacterial species and their topographical distribution revealed that the microbial flora in HS lesions reflects commensal flora of the skin. Due to the susceptibility rate and immunomodulatory and anti-inflammatory properties, cotrimoxazole may represent an alternative antibiotic agent and should be considered for therapy in HS patients.

A pilot study of quality of life in German prehospital emergency care physicians.

BACKGROUND: Quality of life in patients represents an important area of assessment. However, attention to health professionals should be equally important. The literature on the quality of life (QOL) of emergency physicians is scarce. This pilot study investigated QOL in emergency physicians in Germany. MATERIALS AND METHODS: We conducted a cross-sectional study from January to June in 2015. We approached the German Association of Emergency Medicine Physicians and two of the largest recruitment agencies for emergency physicians in Germany and invited their members to participate. We used the WHO Q-BREF to obtain QOL scores in four domains that included physical, mental, social, and environmental health. RESULTS: The 478 German emergency physicians included in the study held board certifications in general medicine (n = 40; 8.4%), anesthesiology (n = 243; 50.8%), surgery (n = 63; 13.2%), internal medicine (n = 81; 17.0%), or others (n = 51; 10.7%). The women surveyed tended to report a better QOL but worse general health than the men. Regarding specific domains, women scored worse in physical health, particularly energy during everyday work (relative risk ratio [RRR]: 1.98 [1.21-3.24]). Both men and women scored worse in psychological health than general health, particularly young women. Women were also more likely to view their safety (RRR: 1.87 [1.07-3.28]) and living place (RRR: 2.51 [1.10-5.73]) as being poor than their male counterparts. CONCLUSION: QOL in German prehospital emergency care physicians is satisfactory for the included participants; however, there were some negative effects in the psychological health domain. This is particularly obvious in young female emergency physicians.

Correlation of inflammatory serum markers with disease severity in patients with hidradenitis suppurativa (HS).

BACKGROUND: Data regarding the association of routinely obtained serum markers of inflammation, namely C-reactive protein (CRP), white blood cell count, and neutrophil count, with disease severity of hidradenitis suppurativa (HS) according to a scoring system have not been reported to our knowledge. OBJECTIVE: We sought to evaluate these inflammatory serum markers for assessing disease severity of HS. METHODS: Medical files of 275 patients who were referred to the outpatient HS center of the Department of Dermatology, Venereology, and Allergology, Ruhr-University Bochum, in 2013 were evaluated retrospectively. RESULTS: CRP levels and neutrophil count significantly differed among Hurley stages I, II and III (P < .0001, P = .0002, respectively). There were significant positive correlations among CRP levels (r = 0.496, P < .0001) and neutrophil count (r = 0.330, P = .0009) with modified Hidradenitis Suppurativa Score. CRP was a significant independent predictor for Hurley stage III (odds ratio 1.077, 95% confidence interval 1.013-1.145, P = .016). CRP and body mass index were significant independent predictors for severe disease according to modified Hidradenitis Suppurativa Score (odds ratio 1.065, 95% confidence interval 1.015-1.117, P = .009; and odds ratio 1.12, 95% confidence interval 1.009-1.243, P = .032, respectively). LIMITATIONS: Files were analyzed retrospectively. CONCLUSION: These inflammatory markers, especially CRP, are effective for assessing the extent of disease severity and the grade of inflammation in patients with HS.

Laser and light-based treatment options for hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that commonly develops painful, deep dermal abscesses and chronic, draining sinus tracts. Classically, pharmacologic and surgical therapies have been effective for reducing lesion activity and inflammation, but provide only modest success in the prevention of future recurrences and disease progression. Adjunctive therapies, such as laser and light-based therapies, have become more commonly used in the management of HS. These therapies work to reduce the occurrence of painful HS flare-ups by decreasing the number of hair follicles, sebaceous glands, and bacteria in affected areas, and by ablatively debulking chronic lesions. The best results are seen when treatment is individualized, taking disease severity into consideration when selecting specific energy-based approaches. This article will discuss various light-based therapies and the evidence supporting their use in the management of HS.

Scar hinge flap for inner lining reconstruction of full-thickness defects on the ala of the nose.

BACKGROUND: Reconstruction of inner lining of the nose often requires complex surgical procedures. METHODOLOGY: To evaluate the scar hinge flap as an alternative reconstruction technique, 21 patients with full-thickness defects of the ala who received a scar hinge flap were retrospectively analysed. RESULTS: Twenty-one patients were included. The average defect size was 1.9 cm2. Cartilage grafts were used in 11 patients. For skin reconstruction the scar hinge flap was covered by local flaps, interpolated melolabial flaps, full-thickness skin grafts, or paramedian forehead flaps. The mean follow-up was 10.7 months. No severe complications were observed. CONCLUSIONS: The scar hinge flap is a safe and simple technique for reconstruction of the inner lining of the nose although it is limited being a two-stage procedure.

The keystone flap: expanding the dermatologic surgeon's armamentarium.

First described in 2003, the keystone flap has become an established plastic and reconstructive surgery technique for the closure of soft tissue defects following the excision of skin tumors. Complex reconstruction procedures may thus be avoided [3]. In dermatosurgery, however, the keystone flap remains largely unknown.Compared to subcutaneous pedicle flaps, the keystone flap technique warrants better vascular supply by additional-ly preserving musculocutaneous and fasciocutaneous perforator vessels [4]. Moreover, the flap is hyperemic compared to the surrounding skin [5]. Adequate perfusion and its specific design result in high safety of the flap. According to both published data and the authors' experience, the keystone flap technique is associated with a low complication rate [1, 6].In summary, the keystone flap method yields good aesthetic and functional results by preserving shape and cont-our, avoiding differences in skin coloration and preserving sensitivity (Figure 1b). The flap is particularly well suited for deep defects with exposed bones or tendons, especially on the extremities or the trunk. Alternative closing options such as secondary intention healing, primary closure, or local flaps appear less adequate in these cases. In addition, skin grafting without long-term wound conditioning­for example negative pressure wound therapy­or expensive der-mal replacement products are not very promising. Thus, the keystone flap provides the dermatosurgeon with an effective alternative to reconstruction techniques.

Bacteribilia with resistant microorganisms after preoperative biliary drainage--the influence of bacteria on postoperative outcome.

BACKGROUND: In pancreatic surgery, preoperative biliary drainage (PBD) leads to bacteribilia. Whether positive bile duct cultures are associated with a higher postoperative morbidity might be related to the resistance of the species isolated from bile. STUDY: Intraoperative bile duct cultures were collected from all patients who underwent pancreatic surgery. Postoperative morbidity was analyzed according to the species and the resistance found on bile duct cultures. RESULTS: Fifty-five percent (166/301) of patients had PBD, while 45% (135/301) underwent primary operation. PBD was associated with a positive bile duct culture in 87% (144/166) versus 21% (28/135) in patients without PBD (p = 0.001) and polymicrobial infections in 53% (88/166) versus 6% (8/135) (p = 0.001). Postoperative morbidity was 40% (121/301); mortality was 3% (9/301). PBD was not associated with morbidity and mortality, but resistant species on bile duct cultures lead to significantly more postoperative complications, 54% (25/46) versus 38% (96/255) (p = 0.033), with significantly more antibiotic therapies. CONCLUSION: PBD is associated with polymicrobial infections with resistant microorganisms, resulting in more postoperative complications. Since PBD cannot always be avoided, surgeons and gastroenterologists must be aware of their institutional surveillance data to identify patients at risk for postoperative complications.

Identification of Biomarkers and Critical Evaluation of Biomarker Validation in Hidradenitis Suppurativa: A Systematic Review.

IMPORTANCE: The identification and validation of biomarkers in hidradenitis suppurativa (HS) has potential to improve the understanding and management of this chronic, burdensome disease. OBJECTIVE: To systematically identify all known HS biomarkers, categorize them by biomarker type, and critically evaluate their validity according to established criteria. EVIDENCE REVIEW: Eligibility criteria for this review (PROSPERO Registration 230830) included randomized clinical trials, uncontrolled clinical trials, cohort studies, case-control studies, and other observational studies with no restrictions of patient age, sex, race or ethnicity, or language of publication up until December 31, 2020. All articles were categorized into biomarker type, defined using the US Food and Drug Administration Biomarkers, Endpoints, and other Tools (BEST) glossary. Assessment of each identified biomarker was undertaken in line with the US Food and Drug Administration and European Medicines Agency guidelines for the validation of proposed biomarkers. Assessment of the strength of overall data regarding individual biomarkers was undertaken using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. FINDINGS: A total of 3953 nonduplicate articles were screened, of which 1429 articles were retrieved based on the include/exclusion criteria applied. After full-text screen and data extraction, 106 articles were included in this review. The evidence of strength of 6 categories of biomarkers (susceptibility/risk, diagnostic, monitoring, predictive, prognostic, and pharmacodynamic/response biomarkers) was assessed using GRADE criteria. A total of 48 biomarkers were identified with a minimum GRADE rating of moderate. Only 1 diagnostic (serum IL-2R), 1 monitoring (dermal Doppler vascularity), and 2 predictive biomarkers (epithelialized tunnels and positive family history of HS) achieved a GRADE rating of high. None of the identified biomarkers had sufficient clinical validity to be recommended for routine use in the clinical setting. CONCLUSIONS AND RELEVANCE: Major barriers to the identification, validation, and introduction of routine biomarkers in the management of HS include lack of independent biomarker validation studies (especially assumption-free "omics"-based techniques); insufficient assessment of collinearity between identified or proposed biomarkers; and a lack of routine integration of biomarkers into the structure of clinical trials. International consensus among researchers, clinicians, and pharmaceutical stakeholders is required to standardize goals and methods and encourage biomarker integration into future HS clinical trials. This systematic review presents a number of priorities for near-term future research to overcome such barriers and limitations of biomarkers in HS.