Burnout Syndrome, Anxiety, and Depression in Dermatology Residents: A Cross-Sectional Study. / Síndrome de burnout, ansiedad y depresión en residentes de dermatología: un estudio transversal.

BACKGROUND AND OBJECTIVE: Burnout syndrome is a mental health disorder due to chronic occupational stress. Both burnout and associated comorbidities are prevalent among health care professionals, being medical residents a vulnerable group. Despite this, the scientific medical literature currently available on this issue in dermatology residents is scarce. The aim of this study was to analyze the prevalence of the burnout syndrome, anxiety, and depression in dermatology residents, and the associated risk factors. MATERIAL AND METHOD: This was a cross-sectional trial designed to include dermatology residents from Spain (from December 2022 through June 2023). A self-administered form was sent via online messaging applications, including validated scales to study professional quality of life, burnout syndrome, anxiety, and depression. RESULTS: A total of 48 dermatology residents were included in the study, 50% of whom (24/48) were women, with a mean age of 27 years (1.25). A total of 58.33% (28/48) of the residents had some degree of anxiety, 22.9% (11/48) some degree of depression, and 23.4% a moderate risk of burnout (11/48). Workload was the main risk factor associated with the 3 disorders studied, while managerial support or intrinsic motivation seem to play a protective role. CONCLUSIONS: Burnout syndrome and its comorbidities are both prevalent in dermatology residents in Spain and closely related to each other.

Impact of COVID-19 Pandemic on Cutaneous Squamous Cell Carcinoma: A Single-Centre Study of Epidemiologic, Clinic and Histopathological Factors.

BACKGROUND: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. OBJECTIVE: To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. MATERIAL & METHODS: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. RESULTS: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. CONCLUSIONS: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future.

Impact of COVID-19 Pandemic on Cutaneous Squamous Cell Carcinoma: A Single-Centre Study of Epidemiologic, Clinic and Histopathological Factors. / [Artículo traducido] Impacto de la pandemia COVID-19 en el carcinoma de células escamosas cutáneo: un estudio unicéntrico de los factores epidemiológicos, clínicos e histopatológicos.

BACKGROUND: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. OBJECTIVE: To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. MATERIAL & METHODS: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. RESULTS: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. CONCLUSIONS: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future.

Quality of Professional Life Among Dermatologists: Impact of the COVID-19 Pandemic and Suggestions for Improvement. / Calidad de vida profesional en dermatología: impacto de la pandemia y propuestas de mejora.

BACKGROUND AND OBJECTIVE: Quality of professional life (QPL) is defined as a sense of well-being derived from a balance between the challenges of work and the resources available to deal with them. Impaired QPL can contribute to burnout. The aim of this study was to evaluate QPL in Spanish dermatologists using a validated questionnaire. MATERIAL AND METHODS: We designed a cross-sectional study in which Spanish dermatologists were invited to complete an online questionnaire sent out by messaging applications. The dermatologists were asked to provide sociodemographic information, answer 3 open questions, and complete the 35-item Spanish QPL questionnaire (Spanish abbreviation, CVP-35). RESULTS: We analyzed the information submitted by 106 dermatologists (62 women, 58%) with a mean age of 41 years (95% CI, 43.3-38.8 years). Women and department heads scored significantly higher in the workload domain of the questionnaire (P=.02 and P=.005, respectively). A heavy caseload was mentioned as the main factor contributing to impaired QPL and the main change in the wake of the COVID-19 pandemic. CONCLUSIONS: Female dermatologists reported heavier workloads. Heavy caseloads and more remote work were the main changes identified after the COVID-19 pandemic. Heavy caseloads have a significant impact on the QPL of dermatologists in Spain. Reducing caseloads would improve general job satisfaction and quality of care provision.

Skin adverse events related to personal protective equipment: a systematic review and meta-analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic that has spread all over the word. To avoid the virus transmission, healthcare workers must wear adequate personal protective equipment (PPE). PPE is associated with several side events, including skin reactions. The objective of this study was to summarize the prevalence, type and risk factors for cutaneous adverse events related to PPE and prevention measures to avoid them. A systematic review and meta-analysis was conducted using MEDLINE, Scopus and EMBASE databases from conception to 21 January 2021. All types of epidemiological studies regarding skin adverse events related to PPE were included. The literature search identified 1007 references, 35 of them met the eligible criteria and were included for analysis, representing 31 453 participants. The media of skin side events related to PPE was 75.13%. The rate of cutaneous adverse events related to mask was 57.71%, and those associated with gloves and hand hygiene products was 49.16%. Most common skin adverse events were contact dermatitis, acne and itching. The most damaged anatomical regions were the nasal bridge, the cheeks and the hands. The duration of PPE wearing was the most common risk factor. Frequent handwashing, gloves and masks were the agents most frequently related to skin reactions. N95 respirators were the most harmful mask type for the skin. Hydrocolloid use prevented from developing skin adverse events related to masks. In conclusion, the rate of cutaneous adverse events related to PPE use is high. A longer duration of PPE wearing was the most common risk factor. Using hydrocolloid could prevent from skin injuries related to mask use.

Hyaluronic acid biomaterial for human tissue-engineered skin substitutes: Preclinical comparative in vivo study of wound healing.

BACKGROUND: There is not an ideal biomaterial for tissue-engineered skin substitutes (TESSs), and most of the studies or existing therapies use xenogeneic origin natural biomaterials or biosynthetic scaffolds. OBJECTIVE: To analyse clinical, histological integration and homeostasis parameters of a human TESS manufactured with fibrin-hyaluronic acid biomaterial (HA-Skin), grafted in immunodeficient mice for 8 weeks, and compared with the gold standard treatment (Autograft), a human TESS manufactured with fibrin-agarose biomaterial (AG-Skin) and secondary wound healing dressings. METHODS: Human TESSs and autografts were implanted into BALB/c mice after surgical excision. Secondary wound healing approach was achieved with biosynthetic collagen wound dressing (Biobrane® ) and fibrin-hyaluronic acid or fibrin-agarose biomaterial without cells (Total N = 44). Clinical integration and homeostasis parameters were evaluated every two weeks for two months. Histological and immunohistochemical analyses were performed four and eight weeks after grafting. RESULTS: HA-Skin, AG-Skin and Autograft groups showed a proper clinical integration and epithelization eight weeks later. Scar evaluation revealed better results for Autograft and HA-Skin. Homeostasis analysis indicated similar values of transepidermal water loss and elasticity between HA-Skin (6.42 ± 0.75 g/h/m2 , 0.42 ± 0.08 AU), Autograft (6.91 ± 1.28 g/h/m2 , 0.40 ± 0.08 AU) and healthy mouse skin (6.40 ± 0.43 g/h/m2 , 0.35 ± 0.03 AU). Histological results showed that human TESSs and autografts presented better skin structuration and higher expression of cytokeratins. CONCLUSIONS: This study suggests that human TESS based on fibrin-hyaluronic acid biomaterial could be suitable for clinical application in the treatment of several dermatological pathologies (wound healing).

Chromatin immunoprecipitation and high throughput sequencing of SVCV-infected zebrafish reveals novel epigenetic histone methylation patterns involved in antiviral immune response.

Chromatin immunoprecipitation (ChIP) and high throughput sequencing (ChIP-seq) have been used to assess histone methylation (epigenetic modification) dynamics within the internal organs of zebrafish after spring viremia of carp virus (SVCV) infection. Our results show H3K4me3 up-methylation in gene promoters associated with innate immune response during the first 5 days after SVCV infection. Gene Ontology (GO) enrichment analysis confirmed up-methylation in 218 genes in the "immune system process" category. In particular, the promoters of interferon (ifn), interferon stimulated genes (isg), Toll-like receptors (tlr) and c-reactive protein (crp) multi gene sets were marked with the permissive H3K4 methylation. Higher histone 3 methylation was associated with higher transcription levels of the corresponding genes. Therefore, the evidence presented here suggests that transcriptional regulation at the promoter level of key immune genes of the interferon signaling pathway and c-reactive proteins genes can be modulated by epigenetic modification of histones. This study emphasizes the importance of epigenetic control in the response of zebrafish to SVCV infection.

Studying the effect of systemic and biological drugs on intima-media thickness in patients suffering from moderate and severe psoriasis.

BACKGROUND: Psoriasis has been related to a large number of cardiovascular risk factors such as hypertension, diabetes mellitus and arteriosclerosis. The increased carotid intima-media thickness (IMT) could be considered to be a marker of generalized arteriosclerosis. OBJECTIVE: To assess the effect of systemic and biological drugs on psoriatic patients' carotid IMT. METHODS: A prospective study was performed. We studied 53 patients with moderate and severe psoriasis from our psoriasis dermatological unit, analysing lipid and glucose metabolism and performing a carotid IMT sonography before introduction of systemic and biological drugs. After that, we performed an 8-month closely analytic and sonographic follow-up. RESULTS: The IMT of the patients with psoriasis treated with biological drugs tended to decrease, although this occurrence was not statistically significant (P = 0.086). The subgroup analysis revealed that patients treated with methotrexate (P = 0.045) and anti-IL-12/23 (P = 0.010) presented a decrease in their IMT levels. This analysis also showed a decrease in glycaemia and insulin levels in patients treated with TNF-alpha inhibitors and ustekinumab. CONCLUSIONS: Our study suggests that the carotid IMT may benefit from treatment with biological drugs, particularly anti-IL-12/23 and methotrexate in patients suffering from moderate and severe psoriasis. However, larger longitudinal studies should be performed to fully confirm these results.

CLOVES syndrome: review of a PIK3CA-related overgrowth spectrum (PROS).

Overgrowth syndromes are characterized by global or localized disproportionate growth associated with other anomalies, including vascular malformations and neurological and/or visceral disorders. CLOVES (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal naevi, Scoliosis/Skeletal and spinal anomalies) is an overgrowth syndrome caused by mosaic activating mutation in gene PIK3CA, which gives rise to abnormal PI3K-AKT-mTOR pathway activation. These mutations are responsible for the clinical manifestations of the syndrome, which include low- and high-flow vascular malformations, thoracic lipomatous hyperplasia, asymmetric growth, and visceral and neurological disorders. These common anomalies are illustrated with figures from two personal cases. Identification of the clinical and genetic characteristics of CLOVES syndrome is crucial for the differential diagnosis with other overgrowth syndromes, such as Proteus or Klippel-Trenaunay (K-T) syndromes, and for the therapeutic management of the different anomalies. In this context, a new entity comprising different syndromes with phenotypic mutations in PIK3CA has been proposed, designated PIK3CA-related overgrowth spectrum (PROS), with the aim of facilitating clinical management and establishing appropriate genetic study criteria.

Increased expression of microRNA-155 in peripheral blood mononuclear cells from psoriasis patients is related to disease activity.

BACKGROUND: MicroRNAs (miRNAs) gene expression regulators are altered in psoriasis suggesting their role in the pathogenesis. OBJECTIVE: To study expression changes of inflammation and toll-like receptor (TLR)-related miRNAs, miRNA-155, let-7i, miRNA-21, miRNA-146a and miRNA-223 in peripheral mononuclear cells (PBMCs) and miRNA-21, miRNA-146a and miRNA-223 in plasma, from chronic plaque-type psoriasis patients who were treatment-naive or had undergone a washout period (n = 11). MiRNAs were evaluated at baseline and after 11 (9-12) months [median (25th-75th percentile range)] of methotrexate (MTX) or topical (betamethasone plus calcipotriene) treatment. METHODS: MiRNA expression was analysed with quantitative real-time reverse transcription-polymerase chain reaction. Matched controls were studied. RESULTS: Psoriasis patients presented, at baseline, increased expression of miRNA-155, let-7i, miRNA-146a, miRNA-21 and miRNA-223 in PBMCs, plus miRNA-21, miRNA-146a and miRNA-223 in plasma. Receiver-operator characteristic (ROC) curve analysis and area under the curve (AUC) showed that expression of these miRNAs have the potential to distinguish between psoriasis and controls. At baseline, miRNA-155 expression in PBMCs correlated with Psoriasis Area Severity Index (PASI) [12 (8-14)] (Spearman r: 0.7140, P < 0.05) suggesting a role in psoriasis. After MTX or topical treatment, reduction in PASI was observed [87.5% (75-100)]; miRNA-155 expression in PBMCs decreased; plasma miRNA-21, miRNA-146a and miRNA-223 were down-regulated. ROC analysis showed that miRNA-155 expression in PBMCs from psoriasis patients have the potential to distinguish between patients' samples at baseline and after treatment (AUC: 0.942, sensitivity: 0.91; specificity: 0.91 values; maximum likelihood ratio =10). After treatment, miRNA-146a expression in PBMCs increased; miRNA-155/miRNA-146a ratio decreased, suggestive of a regulatory feedback; let-7i expression decreased; miRNA-21 and miRNA-223 remained elevated. CONCLUSION: In this exploratory study, psoriasis patients presented increased expression of miRNA-155 in PBMCs that correlated with PASI and decreased with disease remission. MiRNA-21, miRNA-146a and miRNA-223 in PBMCs and plasma were increased at baseline and differentially modulated, underscoring different roles of TLR-related miRNAs in psoriasis.

Radial scars without atypia in percutaneous biopsy specimens: can they obviate surgical biopsy? / Cicatriz radial sin atipia en biopsia percutánea. ¿Puede evitarse la biopsia quirúrgica?

OBJECTIVE: To evaluate the need for surgical biopsy in patients diagnosed with radial scars without atypia by percutaneous biopsy. MATERIAL AND METHODS: In this retrospective observational study, we selected patients with a histological diagnosis of radial scar in specimens obtained by percutaneous biopsy during an 8-year period. The statistical analysis was centered on patients with radial scar without atypia (we assessed the radiologic presentation, the results of the percutaneous biopsy, and their correlation with the results of surgical biopsy and follow-up) and we added the patients with atypia and cancer in the elaboration of the diagnostic indices. RESULTS: We identified 96 patients with radial scar on percutaneous biopsy; 54 had no atypia, 18 had atypia, and 24 had cancer. Among patients with radial scar without atypia, there were no statistically significant differences between patients who underwent imaging follow-up and those who underwent surgical biopsy (p>0.05). The rate of underdiagnosis for percutaneous biopsy in patients without atypia was 1.9%. The rates of diagnosis obtained with percutaneous biopsy in relation to follow-up and surgical biopsy in the 96 cases were sensitivity 92.3%, specificity 100%, positive predictive value 100%, negative predictive value 97.2%, and accuracy 97.9%. The area under the ROC curve was 0.96 (p<0.001), and the kappa concordance index was 0.95 (p<0.001) CONCLUSIONS: We consider that it is not necessary to perform surgical biopsies in patients with radial scars without atypia on percutaneous biopsies because the rate of underestimation is very low and the concordance between the diagnosis reached by percutaneous biopsy and the definitive diagnosis is very high.

Impact of an influenza vaccine educational programme on healthcare personnel.

Influenza vaccination has been shown to be the most effective preventive strategy to reduce influenza-related morbidity and mortality in high-risk groups. Despite healthcare personnel (HCP) being considered part of such high-risk groups, their vaccination coverage is low in Europe. In January 2012, we distributed an 18-question survey regarding influenza vaccination to HCP at Gregorio Marañon Paediatric Hospital, in Madrid, Spain. After we documented that only ~30% of HCP were vaccinated an educational programme was implemented in October 2012 before the next influenza season. In January 2013, the same survey delivered again to all HCP documented a significant increase in vaccination rates (from 30% to 40%, P = 0·007) mainly among physicians and for patients' protection. In summary we found that a simple and inexpensive educational programme significantly improved the uptake of influenza vaccination in HCP in our centre. Nevertheless, vaccination rates remained low, and broader and updated campaigns are needed to overcome perception barriers.

Screening for Latent Tuberculosis in the Patient With Moderate to Severe Psoriasis Who Is a Candidate for Systemic and/or Biologic Therapy.

Screening to detect latent tuberculosis infection (LTBI) is essential before patients with moderate to severe psoriasis start treatment with biologics and vigilance will continue to be needed during and after such treatment. The most recently analyzed statistics from the BIOBADADERM registry show a 20.5% prevalence of LTBI in psoriasis patients treated with biologics in Spain. Various screening protocols are in effect in different countries according to their levels of endemic TB and bacillus Calmette-Guérin (BCG) vaccination, and there is no consensus on a gold-standard approach to the diagnosis of LTBI. Tuberculin skin testing (TST) continues to be the diagnostic method of choice in spite of its limited sensitivity, mainly in immunocompromised patients. Additional problems include the TST's well-established lack of specificity, errors in application, subjectivity in the interpretation of results (which must be read during a second visit), and lack of privacy; the main advantages of this test are its low cost and ease of application. Most cost-benefit studies are therefore inclined to favor using interferon-γ release assays to detect LTBI because they minimize false positives (especially in BCG-vaccinated individuals), thereby eliminating the extra costs and side effects of unnecessary chemoprophylaxis. We review the methods used for LTBI screening in psoriasis patients who are candidates for biologic therapy. Additionally, given the fact that most guidelines do not currently consider it necessary to screen patients about to start conventional systemic therapy, we discuss the reasons underlying the need for such screening.

Improving the safety of viral DNA vaccines: development of vectors containing both 5' and 3' homologous regulatory sequences from non-viral origin.

Although some DNA vaccines have proved to be very efficient in field trials, their authorisation still remains limited to a few countries. This is in part due to safety issues because most of them contain viral regulatory sequences to driving the expression of the encoded antigen. This is the case of the only DNA vaccine against a fish rhabdovirus (a negative ssRNA virus), authorised in Canada, despite the important economic losses that these viruses cause to aquaculture all over the world. In an attempt to solve this problem and using as a model a non-authorised, but efficient DNA vaccine against the fish rhabdovirus, viral haemorrhagic septicaemia virus (VHSV), we developed a plasmid construction containing regulatory sequences exclusively from fish origin. The result was an "all-fish vector", named pJAC-G, containing 5' and 3' regulatory sequences of ß-acting genes from carp and zebrafish, respectively. In vitro and in vivo, pJAC-G drove a successful expression of the VHSV glycoprotein G (G), the only antigen of the virus conferring in vivo protection. Furthermore, and by means of in vitro fusion assays, it was confirmed that G protein expressed from pJAC-G was fully functional. Altogether, these results suggest that DNA vaccines containing host-homologous gene regulatory sequences might be useful for developing safer DNA vaccines, while they also might be useful for basic studies.

Establishment of a desirable dose using neutral argon plasma to eradicate miliary peritoneal implants: A phase I/II controlled trial.

INTRODUCTION: Neutral argon plasma (NAP) system could meet the requirements to achieve oncological cytoreduction of peritoneal carcinomatosis with miliary lesions, minimizing the associated morbidity. This phase I/II trial aims to establish the desirable dose that is safe and effective in eliminating tumor cells with lower penetration. METHODS: Patients diagnosed with different origins for peritoneal carcinomatosis and miliary implants were selected for the study. The safe and potentially effective dose (desirability) of NAP was evaluated according to three factors: distance (mm), application time (s) and power (%), to evaluate the response variables such as the presence of tumor cells (Y/N) and the depth of penetration. RESULTS: Ten patients and 120 samples were evaluated and treated with NAP. There was no vascular or organ injury intraoperative using a pre-established dose of 100% (coagulation mode) at a distance of 2-3 cm. The distance was found to be correlated with the presence of the tumor cells in ex-vivo analysis, with an OR of 15.4 (4.0-111.4). The time and energy used were protective factors to eliminate tumor cells with an OR of 0.4 (0.1-0.9) and 0.8 (0.8-0.9), respectively. The safest and most effective desirability results were as follows i) energy 80% during 2-4 s with a distance of 2 cm (0.89), and ii) energy 100% during 2-4 s with a distance of 3 cm (0.90). CONCLUSIONS: The use of NAP during a CRS and HIPEC is safe and effective for eradicating tumor cells on the peritoneal surface at suggested doses of energy, distance and duration. TRIAL IDENTIFICATION: ClinicalTrials.gov Identifier: NCT04904042.

External multicentre validation of pseudomyxoma peritonei PSOGI-Ki67 classification.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignant disease. Adding of the Ki67 proliferation index to the PSOGI PMP classification provided two different subcategories of the extensive HG-PMP group (HG-PMP ≤15% and HG-PMP >15%) with different survival in a previous unicentric study. This study aims to carry out an external and multicentre validation of this new proposed classification. METHOD: It was a prospective analysis of samples from a historical and international cohort of patients. A representative area with higher cellular density was used to determine the Ki67%. The Ki67 proliferation index (%) was determined in all the HG-PMP patients. A Cox proportional hazard models and multivariable COX models were used. The Kaplan-Meier method and the two-tailed log-rank test were used to analyse the effect of different PSOGI-Ki67 categories on OS and DFS. Its predictive accuracy was analysed using Harrel's C-index and the ROC curve. The calibration was performed using the calibration plots matching. RESULTS: After exclusions, 349 patients were available for analysis. The 5-years OS were 86% for LG-PMP, 59% for HG-PMP≤15, 38% for HG-PMP>15 and 42% for SRC-PMP (p = 0.0001). The 5-years DFS were 49% for LG-PMP, 35% for HG-PMP≤15, 16% for HG-PMP>15 and 18% SRC-PMP (p = 0.0001). The discrimination capability of PSOGI-Ki67 was validated. CONCLUSION: the PSOGI-Ki67 classification discriminates and predicts the OS and DFS in patients with PMP dividing the HG-PMP category into two well-defined sub-categories. The Ki67 proliferation index should be incorporated routinely in the pathology report for these patients.

Protection and antibody response induced by intramuscular DNA vaccine encoding for viral haemorrhagic septicaemia virus (VHSV) G glycoprotein in turbot (Scophthalmus maximus).

Turbot (Scophthalmus maximus) is a high-value farmed marine flatfish with growing demand and production levels in Europe susceptible to turbot-specific viral haemorrhagic septicaemia virus (VHSV) strains. To evaluate the possibility of controlling the outbreaks of this infectious disease by means of DNA vaccination, the gpG of a VHSV isolated from farmed turbot (VHSV(860)) was cloned into an expression plasmid containing the human cytomegalovirus (CMV) promoter (pMCV1.4-G(860)). In our experimental conditions, DNA immunised turbots were more than 85% protected against VHSV(860) lethal challenge and showed both VHSV-gpG specific and neutralizing antibodies. To our knowledge this is the first report showing the efficacy of turbot genetic immunisation against a VHSV. Work is in progress to determine the contribution of innate and adaptive immunity to the protective response elicited by the immunization.