Characterization of Surgical Procedures in the Spanish Mohs Surgery Registry (REGESMOHS) for 2013-2015. / Descripción de las intervenciones quirúrgicas recogidas en el registro español de cirugía de Mohs (REGESMOHS) (2013-2015).

INTRODUCTION: The Spanish Mohs Surgery Registry is used to collect data on the use and outcomes of Mohs micrographic surgery (MMS) in Spain. The aim of this study was to describe perioperative and intraoperative data recorded for MMS procedures performed between July 2013 (when the registry started) and January 2016. MATERIAL AND METHODS: Prospective cohort study of data from 18 hospitals. The data collected included type of anesthesia, surgical technique, hospital admission, number of Mohs stages, management of preoperative risk factors, additional treatments, previous treatments, type of tumor, operating time, and complications. RESULTS: Data were available for 1796 operations. The most common tumor treated by MMS was basal cell carcinoma (85.96%), followed by squamous cell carcinoma (6.18%), lentigo maligna (2.81%), and dermatofibrosarcoma protuberans (1.97%). Primary tumors accounted for 66.9% of all tumors operated on; 19.2% of tumors were recurrent and 13.9% were persistent. The most common previous treatment was surgical. MMS was mostly performed under local anesthesia (86.7% of cases) and as an outpatient procedure (71.8%). The frozen section technique was used in 89.5% of cases. One stage was needed to achieve tumor-free margins in 56.45% of patients; 2 stages were required in 32.1% of patients, 3 in 7.1%%, 4 in 2.7%, and 5 or more in 1.8%. The defect was reconstructed by the dermatologist in 98% of patients and the most common technique was flap closure (47.2%). Intraoperative complications were recorded for just 1.62% of patients and the median (interquartile range) duration of surgery was 75 (60-100) minutes. CONCLUSION: The characteristics of the patients and tumors treated by MMS are similar to those reported for similar studies in other geographic areas. Lentigo maligna and dermatofibrosarcoma protuberans accounted for a higher proportion of cases in our series, and repair of the surgical defect by a dermatologist was also more common. Operating times in MMS are not much longer than those reported for other procedures and the rate of intraoperative complications is very low.

Description of Patients Undergoing Mohs Surgery in Spain: Initial Report on Data From the Spanish Registry of Mohs Surgery (REGESMOHS).

INTRODUCTION: The Spanish registry of Mohs micrographic surgery started collecting data in July 2013. The aim of the registry is to report on the use of this technique in Spain and the outcomes achieved. In the present article, we describe the characteristics of patients and the tumors treated. MATERIAL AND METHODS: This is a prospective cohort study of patients treated with Mohs micrographic surgery. The participating centers are hospitals where at least one intervention of this type is performed each week. All patients considered for Mohs micrographic surgery in participating centers are included in the registry except those who have been declared legally incompetent. RESULTS: Between July 2013 and October 2014, data from 655 patients were included in the registry. The most common tumor involved was basal cell carcinoma, and the most common histological subtype was infiltrative basal cell carcinoma. Most of the tumors treated were located on the face or scalp, and the most common site was the nose. Almost 40% of the tumors treated were recurrent or persistent, and preoperative tumor size was similar to that reported in other European studies and in Australia. In total, 45.5% of patients had received previous surgical treatment. CONCLUSION: The findings are similar to those reported in other studies, and the data collected are useful for assessing whether the results of studies carried out elsewhere are applicable in Spain.

GALV expression enhances the therapeutic efficacy of an oncolytic adenovirus by inducing cell fusion and enhancing virus distribution.

The limitations of the current oncolytic adenoviruses for cancer therapy include insufficient potency and poor distribution of the virus throughout the tumor mass. To address these problems, we generated an oncolytic adenovirus expressing the hyperfusogenic form of the gibbon-ape leukemia virus (GALV) envelope glycoprotein under the control of the adenovirus major late promoter. The oncolytic properties of the new fusogenic adenovirus, ICOVIR16, were analyzed both in vitro and in vivo, and compared with that of its non-fusogenic counterpart, ICOVIR15. Our results indicate that GALV expression by ICOVIR16 induced extensive syncytia formation and enhanced tumor cell killing in a variety of tumor cell types. When injected intratumorally or intravenously into mice with large pre-established melanoma or pancreatic tumors, ICOVIR16 rapidly reduced tumor burden, and in some cases, resulted in complete eradication of the tumors. Importantly, GALV expression induced tumor cell fusion in vivo and enhanced the spreading of the virus throughout the tumor. Taken together, these results indicate that GALV expression can improve the antitumoral potency of an oncolytic adenovirus and suggest that ICOVIR16 is a promising candidate for clinical evaluation in patients with cancer.

Syncytia formation affects the yield and cytotoxicity of an adenovirus expressing a fusogenic glycoprotein at a late stage of replication.

Fusogenic membrane glycoproteins (FMGs) may enhance the cytotoxicity of conditionally replicative adenoviruses. However, expression at early stages of infection impairs virus replication. We have inserted the hyperfusogenic form of the gibbon ape leukemia virus (GALV) envelope glycoprotein as a new splice unit of the major late promoter (MLP) to generate a replication-competent adenovirus expressing this protein. At high multiplicity of infection (MOI), this virus replicated efficiently forming clumps of fused cells and showing a faster release. In contrast, at low MOI, infected cells formed syncytia where only one nucleus contained virus DNA, decreasing total virus production but increasing cytotoxicity.

Effect of incubation temperature on growth parameters of Pseudoalteromonas antarctica NF and its production of extracellular polymeric substancesdagger.

AIM: To evaluate the effect of temperature on growth parameters and on extracellular polymeric substance (EPS) production for Pseudoalteromonas antarctica NF(3). METHODS AND RESULTS: For this purpose, three growth parameters, lag time (lambda), maximum growth rate (mu) and maximum population density (A), were calculated with the predictive Gompertz model. To evaluate the variations in mu with respect to temperature, the secondary Arrhenius and the square root models were used. Below the optimal growth temperature (17.5 degrees C), the growth of P. antarctica was separated into two domains at the critical temperature of 12 degrees C. Within the suboptimal domain (12-17.5 degrees C), the temperature characteristic was the lowest (5.29 kcal mol(-1)). Growth population densities were maintained over the entire physiological portion assayed (5-17.5 degrees C). Higher crude EPS production was found at temperatures included in the cold domain (5-12 degrees C). CONCLUSIONS: All calculated parameters revealed an optimal adaptation of this strain to cold temperatures. SIGNIFICANCE AND IMPACT OF THE STUDY: The knowledge of the influence of temperature on growth parameters of P. antarctica NF(3) and on EPS production could improve the production of this extracellular polymeric substance that is currently being used in the cosmetic and pharmaceutical industries.

A novel pathway producing dimethylsulphide in bacteria is widespread in soil environments.

The volatile compound dimethylsulphide (DMS) is important in climate regulation, the sulphur cycle and signalling to higher organisms. Microbial catabolism of the marine osmolyte dimethylsulphoniopropionate (DMSP) is thought to be the major biological process generating DMS. Here we report the discovery and characterization of the first gene for DMSP-independent DMS production in any bacterium. This gene, mddA, encodes a methyltransferase that methylates methanethiol and generates DMS. MddA functions in many taxonomically diverse bacteria including sediment-dwelling pseudomonads, nitrogen-fixing bradyrhizobia and cyanobacteria, and mycobacteria including the pathogen Mycobacterium tuberculosis. The mddA gene is present in metagenomes from varied environments, being particularly abundant in soil environments, where it is predicted to occur in up to 76% of bacteria. This novel pathway may significantly contribute to global DMS emissions, especially in terrestrial environments and could represent a shift from the notion that DMSP is the only significant precursor of DMS.

Genetic background determines the response to adenovirus-mediated wild-type p53 expression in pancreatic tumor cells.

The development of new therapies is particularly urgent with regard to pancreatic tumors. Gene therapy approaches involving p53 replacement are promising due to the central role of p53 in the cellular response to DNA damage and the high incidence of p53 mutations in pancreatic tumors. Adenoviruses containing wild-type (wt) p53 cDNA (Ad5CMV-p53) were introduced into four human pancreatic cell lines to examine the impact caused by exogenous wt p53 on these cells. Introduction of wt p53 in mutant p53 cells (NP-9, NP-18, and NP-31) caused marked falls in cell proliferation and rises in the level of apoptosis. In contrast, overexpression of p53 did not induce apoptosis in NP-29 (wt p53). The presence of p16 contributes to the induction of apoptosis, as demonstrated by introduction of the wt p16 gene (Ad5RSV-p16). Analysis of cell cycle and apoptosis in etoposide-treated cells corroborated the inability of NP-29 to die by apoptosis, suggesting that this wt p53 cell line lacks p53 downstream functions in the apoptosis pathway. Taken together, our results indicate that the effects elicited by exogenous p53 protein depend upon the molecular alterations related to p53 actions on cell cycle and apoptosis. Therefore, knowledge of the genetic background of tumor cells is crucial to the development of efficient therapies based on the introduction of tumor suppressor genes.

[Valvular regurgitation caused by anorectic agents]. / Regurgitación valvular causada por fármacos anorexígenos.

Valvular heart disease associated with the use of anorectic agents is a recently described clinical entity. We report the case of a 46-year-old woman with severe regurgitation of the mitral, aortic and tricuspid valves who had been taking fenfluramine and dexfenfluramine for two years. Surgical treatment was required with replacement of three valve by mechanical prostheses. The previous history of treatment with anorectic agents, the echocardiographic morphology of the injured valves and the macroscopic and histopathologic findings strongly suggested an association between the anorectic agents and the valvular disease of the patient.

Descripción de las intervenciones quirúrgicas recogidas en el registro español de cirugía de Mohs (REGESMOHS) (2013-2015) / Characterization of Surgical Procedures in the Spanish Mohs Surgery Registry (REGESMOHS) for 2013-2015

Introducción: El Registro Español de Cirugía de Mohs recoge los datos de aplicación y resultados de esta técnica en España. Se describen los datos de las intervenciones realizadas desde el inicio del Registro en julio de 2013 a enero de 2016. Se analizan los datos de las cirugías tanto perioperatorios como intraoperatorios. Material y métodos: Estudio de cohortes prospectivo en el que participan 18 centros. Se recogen los datos de las intervenciones quirúrgicas como tipo de anestesia, técnica quirúrgica, ingreso hospitalario, número de estadios, manejo de factores de riesgo preoperatorios, tratamientos complementarios, tratamientos previos, tipo de tumor, tiempo empleado en la cirugía y complicaciones. Resultados: Se analizan 1.796 intervenciones quirúrgicas. El tumor intervenido con más frecuencia es el carcinoma basocelular (85,96%), seguido del carcinoma epidermoide (6,18%), lentigo maligno (2,81%) y dermatofibrosarcoma protuberans (1,97%). El 66,9% de los tumores eran primarios, el 19,2% recurrentes y el 13,9% persistentes. El tratamiento previo más frecuente fue quirúrgico. La cirugía de Mohs se realizó con más frecuencia bajo anestesia local (86,7%) y de forma ambulatoria (71,8%). En el 89,5% de los casos se utilizó la técnica de Mohs en congelación. El número de etapas requerido para alcanzar márgenes libres de tumor fue una en 56,45% de los pacientes, 2 en 32,1%, 3 en 7,1%, 4 en 2,7% y 5 o más en 1,8%. El propio dermatólogo reconstruyó el defecto en el 98% de los pacientes y la técnica reconstructiva más utilizada fue el colgajo (47,2%). Solo el 1,62% de los pacientes presentó alguna complicación intraoperatoria y la mediana de la duración de la cirugía fue 75 (p25:60-p75:100). Conclusión: Las características de los pacientes y tumores tratados son similares a las descritas en estudios de las mismas características en otras áreas geográficas. Existe un porcentaje mayor de lentigo maligno y dermatofibrosarcoma protuberans. La reconstrucción la realiza el dermatólogo con más frecuencia que en otras series. El tiempo de utilización de quirófano no es mucho mayor que para otras técnicas y la tasa de complicaciones intraoperatorias es muy reducida (AU)

Introduction: The Spanish Mohs Surgery Registry is used to collect data on the use and outcomes of Mohs micrographic surgery (MMS) in Spain. The aim of this study was to describe perioperative and intraoperative data recorded for MMS procedures performed between July 2013 (when the registry started) and January 2016. Material and methods: Prospective cohort study of data from 18 hospitals. The data collected included type of anesthesia, surgical technique, hospital admission, number of Mohs stages, management of preoperative risk factors, additional treatments, previous treatments, type of tumor, operating time, and complications. Results: Data were available for 1796 operations. The most common tumor treated by MMS was basal cell carcinoma (85.96%), followed by squamous cell carcinoma (6.18%), lentigo maligna (2.81%), and dermatofibrosarcoma protuberans (1.97%). Primary tumors accounted for 66.9% of all tumors operated on; 19.2% of tumors were recurrent and 13.9% were persistent. The most common previous treatment was surgical. MMS was mostly performed under local anesthesia (86.7% of cases) and as an outpatient procedure (71.8%). The frozen section technique was used in 89.5% of cases. One stage was needed to achieve tumor-free margins in 56.45% of patients; 2 stages were required in 32.1% of patients, 3 in 7.1%%, 4 in 2.7%, and 5 or more in 1.8%. The defect was reconstructed by the dermatologist in 98% of patients and the most common technique was flap closure (47.2%). Intraoperative complications were recorded for just 1.62% of patients and the median (interquartile range) duration of surgery was 75 (60-100) minutes. Conclusion: The characteristics of the patients and tumors treated by MMS are similar to those reported for similar studies in other geographic areas. Lentigo maligna and dermatofibrosarcoma protuberans accounted for a higher proportion of cases in our series, and repair of the surgical defect by a dermatologist was also more common. Operating times in MMS are not much longer than those reported for other procedures and the rate of intraoperative complications is very low (AU)

Descripción de los pacientes intervenidos mediante cirugía de Mohs en España. Datos basales del registro español de cirugía de Mohs (REGESMOHS) / Description of Patients Undergoing Mohs Surgery in Spain: Initial Report on Data From the Spanish Registry of Mohs Surgery (REGESMOHS)

INTRODUCCIÓN: En julio de 2013 se inició la recogida de datos del registro español de cirugía micrográfica de Mohs, que describe la aplicación y los resultados de esta técnica en España. En este artículo se describen las características del paciente y de los tumores tratados. MATERIAL Y MÉTODOS: Se trata de un estudio de cohortes prospectivo en el que participan centros en los que se practica al menos una intervención semanal de cirugía micrográfica de Mohs. En cada centro se incluyen todos los pacientes que son valorados para realizar cirugía de Mohs, excepto los declarados judicialmente incapaces. En este artículo describimos las características de los pacientes y los tumores incluidos en la cohorte. RESULTADOS: El número de pacientes incluidos desde julio de 2013 hasta octubre de 2014 es de 655. La mayoría de los tumores cutáneos intervenidos correspondieron a carcinoma basocelular, siendo el infiltrante el subtipo histológico más frecuente. La mayoría de las cirugías se practicaron en tumores localizados en la cara y el cuero cabelludo, siendo la localización más frecuente la nariz. Casi el 40% de los tumores operados son recurrentes o persistentes, y el tamaño tumoral prequirúrgico es similar en nuestro medio al descrito en otros estudios australianos o europeos. Hasta el 45,5% de los pacientes había recibido algún tratamiento quirúrgico previo. CONCLUSIÓN: Los datos observados son similares a los de otras series publicadas, y son relevantes para poder valorar la aplicabilidad en nuestro contexto de estudios realizados en otros medios

INTRODUCTION: The Spanish registry of Mohs micrographic surgery started collecting data in July 2013. The aim of the registry is to report on the use of this technique in Spain and the outcomes achieved. In the present article, we describe the characteristics of patients and the tumors treated. MATERIAL AND METHODS: This is a prospective cohort study of patients treated with Mohs micrographic surgery. The participating centers are hospitals where at least one intervention of this type is performed each week. All patients considered for Mohs micrographic surgery in participating centers are included in the registry except those who have been declared legally incompetent. RESULTS: Between July 2013 and October 2014, data from 655 patients were included in the registry. The most common tumor involved was basal cell carcinoma, and the most common histological subtype was infiltrative basal cell carcinoma. Most of the tumors treated were located on the face or scalp, and the most common site was the nose. Almost 40% of the tumors treated were recurrent or persistent, and preoperative tumor size was similar to that reported in other European studies and in Australia. In total, 45.5% of patients had received previous surgical treatment. CONCLUSION: The findings are similar to those reported in other studies, and the data collected are useful for assessing whether the results of studies carried out elsewhere are applicable in Spain

7,10-Dihydroxy-8(E)-octadecenoic acid produced by Pseudomonas 42A2: evaluation of different cultural parameters of the fermentation.

A fermentation process for the microbial production of a new lipid surface-active compound, 7,10-dihydroxy-8 (E)-octadecenoic acid (OCD), has been established using a vegetable oil as carbon source in a coordinated carbon/nitrogen feed strategy. The surfactant was produced during the logarithmic growth phase. Aeration was the most critical parameter for product formation. Up to 7 g product/l was produced.

[Characteristics of AIDS cases detected at a prison in Barcelona (1991-1993)]. / Características de los casos de SIDA detectados en una prisión de Barcelona (1991-1993).

OBJECTIVE: To describe the cases of AIDS detected in a Barcelona prison. DESIGN: A prospective study. SETTING: A penitentiary for men in Barcelona. PATIENTS: All those inmates who had AIDS or were diagnosed with the illness during their stay in prison during the 36 months between 1/1/1991 and 31/12/93. RESULTS: 220 cases of AIDS (91.7% PVDA), 60% of which were diagnosed in prison. The PVDA were younger (p < 0.0001). There were a greater number of Spaniards among the UDVP (p < 0.01) and among those with tattoos (p < 0.001). The first manifestation of the disease in 53% of the cases was extrapulmonary Tuberculosis. CONCLUSIONS: Prisons are key places in the prevention and monitoring of HIV infection. The use of care programmes, including maintenance programmes using Methadone, for drug-dependent patients are recommended. The continuation of programmes tracking Tuberculosis, the main illness related to HIV infection in prison, is also recommended.

Enhanced pancreatic tumor regression by a combination of adenovirus and retrovirus-mediated delivery of the herpes simplex virus thymidine kinase gene.

We have evaluated the effectiveness of combining the different characteristics of retrovirus and adenovirus to apply the herpes simplex virus thymidine kinase gene (HSVtk) and ganciclovir (GCV) treatment for gene therapy of pancreatic cancer. Transduction of NP-18 human pancreatic cells in culture by either the adenoviral vector (ADV/tk) or the retroviral vector (Rv/tk) followed by GCV treatment resulted in a GCV dose-dependent cytotoxic effect. A bystander effect was determined, both in NP-18 cultures and in xenogeneic cell mixtures of NP-18 and PA317 cells. Studies in vivo indicated that the effectiveness of tumor regression after HSVtk gene transfer and GCV treatment was dependent first on the tumor size at the time of viral injection and secondly, in large tumors, on the type of virus administered. The administration of the viral combination (ADV/tk + vector producer cells VPC-Rv/tk) was the best approach tested and resulted in a dramatic reduction in tumor mass after 4 days of GCV treatment which was maintained for the treatment period. Remarkably, two animals presented a complete eradication of the tumor. Thus, the HSVtk/GCV system when administered using a viral combination (ADV/tk + VPC-Rv/tk), may be a promising suicide gene therapy for pancreatic carcinomas.

[Coarctation of the aorta. In infancy (author's transl)]. / Coartación aórtica en el lactante.

We review our experience in 38 patients with coarctation of the aorta during infancy. Cardiac failure was present in 30 patients, being the maximal incidence during the first and second weeks of the life. Sixteen infants died, 43% of them during the first week. Cardiac catherization and angiocardiography were performed in 22 infants. The coarctation of the aorta was isolated in 38 infants (36%). The most frequently associated malformations were: patent ductus arteriosus (6 cases), ventricular septal defect (5 cases) and the pathology of the left heart. The post mortem examination was performed in 11 infants; in all of them the CoAo was preductal with patent ductus arteriosus; the most frequently associated malformation was ventricular septal defect (6 cases). 5 infants were operated upon with succes during the first year of the life.

Effects of adenovirus-mediated SV5 fusogenic glycoprotein expression on tumor cells.

BACKGROUND: The fusogenic (F) membrane glycoprotein of the paramyxovirus SV5 allows virus to enter host cells and mediates fusion between neighboring cells, which leads to cell death. F glycoprotein is synthesized as an inactive precursor (F(0)) that is cleaved by cellular protease furine to form the active heterodimer F(1) + F(2). The active protein can induce syncytium formation in the absence of another integral glycoprotein (HN), a property that appears to be unique among paramyxoviruses. METHODOLOGY: We constructed a non-replicative adenovirus to express SV5 F protein in tumor cells, and its fusion capacity was analyzed by fluorescent and confocal microscopy. Cell viability and bystander effect were compared with the thymidine kinase/ganciclovir suicide gene therapy. The structure of F-expressing cells was studied using electron microscopy. RESULTS: F glycoprotein expression induced syncytium formation to a maximum at 72 h, after which syncytia progressively lost viability and detached. The cell membrane was disrupted while nuclear structure was preserved. Over-expression of SV5 F protein in tumor cells led to high cytotoxicity comparable with that associated with the thymidine kinase/ganciclovir. A potent bystander killing effect was detected until the ratio of F-transduced to non-transduced cells was 1 : 100. CONCLUSIONS: These results indicate that the fusogenic glycoprotein of the paramyxovirus SV5 could be used to eliminate tumor cells and may encourage studies aimed at modifying its selectivity and combining its expression with other cytotoxic strategies to improve their efficacy.

Treatment based on a combination of the CYP2B1/cyclophosphamide system and p53 delivery enhances tumour regression in human pancreatic cancer.

BACKGROUND: Strategies based on the introduction of pro-drug activating enzymes or the restoration of tumour suppressor genes have been proposed as encouraging methods to improve the efficiency of treatments in pancreatic cancer. The in situ bioactivation of cyclophosphamide by cytochrome p450-2B1 and subsequent p53 delivery were examined. MATERIALS AND METHODS: NP-18 cell line derived from a human pancreatic adenocarcinoma was treated in vitro with a combination of the Adenovirus-CYP2B1/cyclophosphamide and adenoviral-mediated wt-p53 reintroduction. Cell viability and cytometric cell cycle profiles were analyzed to evaluate the sensitivity of NP-18 cells to this treatment. The efficiency of this combination was assessed in an in vivo model consisting of xenografts into the subcutaneous tissue of Balb/c mice by tumour growth, histological analysis and cell cycle determinations. RESULTS: Ad-CYP2B1/cyclophosphamide or Ad-p53 treatments led to a marked decrease in cell viability of NP-18 cells. Combination of both treatments elicited a higher loss of cell viability and marked increases in sub-G1 population in cell cycle profiles. Animals treated with the combination strategy showed a quick reduction of tumour volumes due to the bioactivation of cyclophosphamide by CYP2B1 and sustained growth inhibition throughout the period evaluated after p53 delivery. Only this group of animals presented statistically significant differences with respect to control and cyclophosphamide-treated groups (P < 0.05). CONCLUSIONS: These results indicate that in situ bioactivation of cyclophosphamide by CYP2B1 and the recognition of the damaged DNA by p53 increase tumour regressions and may be a promising therapy for solid tumour therapy in man.