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.

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.

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.

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.

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.

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.

VHSV G glycoprotein major determinants implicated in triggering the host type I IFN antiviral response as DNA vaccine molecular adjuvants.

We have recently identified the two major determinants of the glycoprotein G of the viral hemorrhagic septicaemia rhabdovirus (gpGVHSV), peptides p31 and p33 implicated in triggering the host type I IFN antiviral response associated to these rhabdoviral antigens. With the aim to investigate the properties of these viral glycoprotein regions as DNA molecular adjuvants, their corresponding cDNA sequences were cloned into a plasmid (pMCV1.4) flanked by the signal peptide and transmembrane sequences of gpGVHSV. In addition, a plasmid construct encoding both sequences p31 and p33 (pMCV1.4-p31+p33) was also designed. In vitro transitory cell transfection assays showed that these VHSV gpG regions were able to induce the expression of type I IFN stimulated genes as well as to confer resistance to the infection with a different fish rhabdovirus, the spring viremia of carp virus (SVCV). In vivo, zebrafish intramuscular injection of only 1µg of the construct pMCV1.4-p31+p33 conferred fish protection against SVCV lethal challenge up to 45 days post-immunization. Moreover, pMCV1.4-p31+p33 construct was assayed for molecular adjuvantcity's for a DNA vaccine against SVCV based in the surface antigen of this virus (pAE6-GSVCV). The results showed that the co-injection of the SVCV DNA vaccine and the molecular adjuvant allowed (i) a ten-fold reduction in the dose of pAE6-Gsvcv without compromising its efficacy (ii) an increase in the duration of protection, and (iii) an increase in the survival rate. To our knowledge, this is the first report in which specific IFN-inducing regions from a viral gpG are used to design more-efficient and cost-effective viral vaccines, as well as to improve our knowledge on how to stimulate the innate immune system.

[Regional cerebral oxygen saturation as a marker of hemodynamic state following cardiac surgery]. / Saturación cerebral de oxígeno como marcador hemodinámico en la cirugía cardíaca.

INTRODUCTION: Regional cerebral oxygen saturation (rSO2) is a measure of the general state of perfusion and oxygenation. We aim to analyze the relationship between this and various hemodynamic and respiratory parameters. PATIENTS AND METHODS: Forty-three patients, operated on between October 2011 and July 2012, were included in this prospective observational descriptive study. The following parameters were measured: mean arterial pressure, both arterial and central venous oxygen saturation and partial pressures of oxygen and carbon dioxide, and lactate levels. From these parameters, the oxygenation index and the oxygen extraction ratio were calculated. These measurements were studied to evaluate whether rSO2 correlated significantly with the other parameters. RESULTS: The average age and weight of the patients were 27.3 months and 9.2 kg, respectively. The rSO2 correlated positively with both central venous oxygen saturation (r=0.73, P<.01) and mean arterial pressure (r=0.59, P<.01), and negatively with the oxygen extraction ratio (r=-0.7, P<.01). No correlation was found with the respiratory parameters. Concordance analysis established an acceptable Kappa index (> 0.4) between the rSO2 and central venous oxygen saturation, and between the rSO2 and oxygen extraction ratio. CONCLUSIONS: Regional cerebral oxygen saturation correlates well with hemodynamic parameters - mean arterial pressure, venous saturation, and the tissue oxygen extraction. However, it does not correlate with respiratory parameters.

[Risk assessment of thrombotic events after the use of activated factor VII]. / Evaluación del riesgo de fenómenos trombóticos tras el uso de factor vii activado.

INTRODUCTION: The objective of this study was to analyze the incidence of thrombotic complications related to recombinant human factor viia (rFVIIa) therapy for severe postoperative bleeding in cardiac surgery. MATERIAL AND METHODS: A retrospective matched case-control study was conducted over two years, including 72 children admitted to intensive care unit and treated with rFVIIa because of a severe bleeding during or after cardiac surgery. A control group of 63 patients was chosen, who were statistically comparable in sex, weight, diagnosis, surgical risk according RASCH-1 score, and surgical characteristics, was chosen. RESULTS: There were no significant differences between cases and controls either in the rate of thrombosis (20% vs 28%, P=.540), or in the mortality rate (16% vs 9.5%, P=.208). CONCLUSIONS: In our study, the rFVIIa therapy was shown to be useful in controlling severe operative bleeding in pediatric cardiac surgery, but does not seem to increase the risk of thrombotic complications or mortality rate in the postoperative period.

Replacement of the human cytomegalovirus promoter with fish enhancer and core elements to control the expression of the G gene of viral haemorrhagic septicemia virus (VHSV).

This work explores some of the possibilities to replace human cytomegalovirus (CMV) core and/or enhancer promoter control elements to create new expression vectors for use with fish. The work is relevant to fish vaccination, since DNA vaccines use eukaryotic expression plasmids controlled by the human cytomegalovirus (CMV) promoter to be effective against novirhabdoviruses, such as viral haemorrhagic septicemia virus (VHSV), one of the most devastating fish viral European diseases. To reduce possible homologous recombination with fish genome, core and enhancer sequences from fish origin, such as trout interferon-inducible myxovirus protein (Mx), zebrafish retrovirus long terminal repeat (LTR) and carp ß-actin (AE6), were combined with those of CMV to design alternative hybrid promoters. The substitution of CMV core and/or enhancer with the corresponding elements of Mx or the LTR core maintained a similar in vitro protein G expression level than that obtained by using the CMV promoter. Vectors using the dsRNA-inducible Mx enhancer followed either by the LTR or the AE6 cores showed the highest in vitro protein G expression levels. Furthermore, synthetic constructs using the Mx enhancer maintained their polyI:C induction capabilities despite the core used. Some of these hybrid promoters might contribute to the development of all-fish-vectors for DNA vaccines while others might be useful for more basic studies.