Identification, Biochemical Characterization, and In Vivo Detection of a Zn-Metalloprotease with Collagenase Activity from Mannheimia haemolytica A2.

Respiratory diseases in ruminants are a main cause of economic losses to farmers worldwide. Approximately 25% of ruminants experience at least one episode of respiratory disease during the first year of life. Mannheimia haemolytica is the main etiological bacterial agent in the ruminant respiratory disease complex. M. haemolytica can secrete several virulence factors, such as leukotoxin, lipopolysaccharide, and proteases, that can be targeted to treat infections. At present, little information has been reported on the secretion of M. haemolytica A2 proteases and their host protein targets. Here, we obtained evidence that M. haemolytica A2 proteases promote the degradation of hemoglobin, holo-lactoferrin, albumin, and fibrinogen. Additionally, we performed biochemical characterization for a specific 110 kDa Zn-dependent metalloprotease (110-Mh metalloprotease). This metalloprotease was purified through ion exchange chromatography and characterized using denaturing and chaotropic agents and through zymography assays. Furthermore, mass spectrometry identification and 3D modeling were performed. Then, antibodies against the 110 kDa-Mh metalloprotease were produced, which achieved great inhibition of proteolytic activity. Finally, the antibodies were used to perform immunohistochemical tests on postmortem lung samples from sheep with suggestive histology data of pneumonic mannheimiosis. Taken together, our results strongly suggest that the 110-Mh metalloprotease participates as a virulence mechanism that promotes damage to host tissues.

Asociación entre el riesgo nutricional, estancia hospitalaria y diagnóstico médico en pacientes de un hospital del seguro social peruano

Objetivo: Determinar la asociación que existe entre el riesgo nutricional, la estancia hospitalaria y el diagnóstico médico en pacientes hospitalizados en el Centro Especializado de Rehabilitación Profesional (CERP) del Hospital Nacional Guillermo Almenara Irigoyen. Materiales y métodos: Se realizó un estudio observacional de cohorte longitudinal, retrospectivo, que incluyó a las personas hospitalizadas durante el periodo comprendido entre el 1 de julio del 2021 y el 27 de febrero del 2022. Hubo un seguimiento de los pacientes hasta su alta del centro hospitalario (egreso). Se excluyeron los individuos menores de 18 años, gestantes o puérperas, y cuya permanencia fue menor a 24 horas. Los datos de interés fueron recogidos a partir de la revisión de las historias clínicas y kárdex de nutrición. La variable principal fue el riesgo nutricional, el cual fue detectado mediante el Nutritional Risk Screening (NRS) 2002; las variables secundarias fueron los grupos etarios, el sexo, la estancia hospitalaria, el diagnóstico médico principal, la condición de egreso y el estado nutricional. En el análisis de los datos, para la comparación de variables cualitativas o categóricas se utilizó la prueba chi-cuadrado y para variables cuantitativas, la prueba t de Student y ANOVA. Se consideró significancia estadística al valor de p < 0,05. Resultados: Se incluyó un total de 1 929 pacientes. La prevalencia del riesgo nutricional fue 33,13 %. Los pacientes con esta condición presentaron tasas de mortalidad más altas (57,51 %). Se observó que la prevalencia del riesgo nutricional está relacionada con una mayor estancia hospitalaria (4,6 días más) (p < 0,001), con el diagnóstico nutricional de delgadez (48,67 %) (p < 0,001) y con el diagnóstico médico, donde la enfermedad oncológica es la más asociada (50,93 %). Conclusiones: El riesgo nutricional se asocia a una evolución negativa de la enfermedad, lo que origina un aumento de la estancia hospitalaria, la tasa de mortalidad y, por ende, los costos intrahospitalarios. Es importante realizar su detección temprana para poder brindar intervenciones nutricionales adecuadas.

Objective: To determine the association between nutritional risk, hospital stay and medical diagnosis among patients admitted at Centro Especializado de Rehabilitación Profesional (CERP) of Hospital Nacional Guillermo Almenara Irigoyen. Materials and methods: An observational retrospective longitudinal cohort study was conducted with inpatients between July 1, 2021 and February 27, 2022. The patients were followed up until they left the hospital (discharge). Individuals under 18 years of age, pregnant or puerperal women, and those whose stay was less than 24 hours were excluded. The data of interest was collected from the patients' medical records and diet cards. The main variable was the nutritional risk, which was detected using the Nutritional Risk Screening (NRS) 2002. The secondary variables were age group, sex, hospital stay, main medical diagnosis, discharge condition and nutritional status. Data analysis was performed using the chi-square test to compare the qualitative or categorical variables, and the Student's t-test and ANOVA for the quantitative variables. A value of p < 0.05 was considered as statistically significant. Results: A total of 1,929 patients were included in the study. Nutritional risk prevalence accounted for 33.13 %. Patients with this condition showed the highest mortality rates (57.51 %). It was found that nutritional risk prevalence was related to a longer hospital stay (4.6 more days) (p < 0.001), a diagnosis of constitutional thinness (48.67 %) (p < 0.001) and the medical diagnosis, being oncology disorders the most associated ones (50.93 %). Conclusions: Nutritional risk is associated with disease progression, resulting in an increased hospital stay, mortality rate and therefore hospital costs. Early detection is important to provide adequate dietary interventions.

Malformación de Chiari tipo I en una embarazada. Reporte de caso / Chiari malformation type I in pregnant women, case report

Resumen ANTECEDENTES: La malformación de Chiari es un padecimiento neurológico, congénito o adquirido, infrecuente. Se caracteriza por el desplazamiento de las estructuras rombencefálicas hacia el canal espinal, por debajo del foramen magno. Se desconoce la frecuencia y evolución que puede tener durante el embarazo porque existen cambios durante el trabajo de parto que pueden predisponer a la herniación del tronco encefálico con compresión medular. Esta situación plantea un desafío terapéutico porque no se dispone de recomendaciones unificadas acerca del momento del parto, vía del nacimiento y mejor técnica anestésica en estas pacientes. CASO CLÍNICO: Paciente primípara, de 24 años, con 34 semanas de embarazo. Acudió a Urgencias del Hospital Universitario de la Samaritana debido a un cuadro clínico de cefalea con signos de alarma. En la resonancia magnética cerebral se encontró una malformación de Chiari tipo I. Con el objetivo de limitar las maniobras de Vasalva durante el trabajo de parto se decidió la cesárea, con anestesia neuroaxial, sin complicaciones y con recién nacido sano. CONCLUSIÓN: La malformación de Chiari tipo I durante el embarazo es infrecuente. Las pacientes con diagnóstico previo al embarazo condicionan un seguimiento en el que se valora la indicación de tratamiento neuroquirúrgico antes de la concepción. Durante el embarazo no puede recomendarse un único método de finalización o anestesia y la atención médica debe estar a cargo un equipo multidisciplinario que formule un plan de atención individualizado para mejorar el desenlace materno y fetal.

Abstract BACKGROUND: Chiari malformation is a rare congenital or acquired neurological disorder, characterized by the displacement of the rhombencephalic structures towards the spinal canal below the level of the foramen magnum; The frequency and progression that can occur during pregnancy are unknown, since there are changes during labor that can predispose to brainstem herniation with spinal cord compression; which poses a therapeutic challenge since there are no unified recommendations about the moment of delivery, delivery route and the best anesthetic technique in these patients CLINICAL CASE: A 24-year-old patient, G1P0 with a 34-week pregnancy, consulted the emergency room of the Hospital Universitario de la Samaritana, due to a clinical profile of headache with warning signs; to the study of cerebral magnetic resonance with a finding of Chiari type I malformation. In order to limit the Valsalva maneuvers during labor, a caesarean section was performed at term under neuraxial anesthesia without complications with a healthy newborn. CONCLUSION: Chiari malformation type I during pregnancy is rare. Patients diagnosed prior to pregnancy condition a follow-up in which the indication for neurosurgical treatment prior to conception is assessed. During pregnancy, no single method of termination or anaesthesia can be recommended and medical care should be provided by a multidisciplinary team formulating an individualized care plan to improve maternal and fetal outcome.

Antimicrobial Activity of Biogenic Silver Nanoparticles from Syzygium aromaticum against the Five Most Common Microorganisms in the Oral Cavity.

Syzygium aromaticum (clove) has been used as a dental analgesic, an anesthetic, and a bioreducing and capping agent in the formation of metallic nanoparticles. The main objective of this study was to evaluate the antimicrobial effect in oral microorganisms of biogenic silver nanoparticles (AgNPs) formed with aqueous extract of clove through an ecofriendly method "green synthesis". The obtained AgNPs were characterized by UV-Vis (ultraviolet-visible spectroscopy), SEM-EDS (scanning electron microscopy-energy dispersive X-ray spectroscopy), TEM (transmission electron microscopy), and ζ potential, while its antimicrobial effect was corroborated against oral Gram-positive and Gram-negative microorganisms, as well as yeast that is commonly present in the oral cavity. The AgNPs showed absorption at 400-500 nm in the UV-Vis spectrum, had an average size of 4-16 nm as observed by the high-resolution transmission electron microscopy (HR-TEM), and were of a crystalline nature and quasi-spherical form. The antimicrobial susceptibility test showed inhibition zones of 2-4 mm in diameter. Our results suggest that AgNPs synthesized with clove can be used as effective growth inhibitors in several oral microorganisms.

Evaluation of possible biomarkers for caries risk in children 6 to 12 years of age.

Background: Electrolytes, proteins, and other salivary molecules play an important role in tooth integrity and can serve as biomarkers associated with caries. Objective: To determine the concentration of potential biomarkers in children without caries (CF) and children with caries (CA). Methods: Unstimulated saliva was collected, and the biomarkers quantified in duplicate, using commercial Enzyme Linked Immunosorbent Assay (ELISA) kits to determine IgA, fibronectin, cathelicidin LL-37, and statherin levels, as well as colorimetric tests to detect formate and phosphate. Results: Significantly higher concentrations of statherin was detected in the CF group (Median: 94,734.6; IQR: 92,934.6-95,113.7) compared to the CA2 group (90,875.0; IQR: 83,580.2-94,633.4) (p = 0.03). Slightly higher median IgA (48,250.0; IQR: 31,461.9-67,418.8) and LL-37 levels (56.1; IQR 43.6-116.2) and a lower concentration of formate were detected in the CF group (0.02; IQR 0.0034-0.15) compared to the group with caries (IgA: 37,776.42; IQR: 33,383.9-44,128.5; LL-37: 46.3; IQR: 40.1011-67.7; formate: 0.10; IQR: 0.01-0.18), but these differences were not statistically significant. Conclusion: The fact that these compounds have been identified as good markers for caries among European adults highlights the difficulty of identifying universal biomarkers that are applicable to all ages or to different populations.

Cold acclimation of mesophyll conductance, bundle-sheath conductance and leakiness in Miscanthus × giganteus.

The cold acclimations of mesophyll conductance (gm ), bundle-sheath conductance (gbs ) and the CO2 concentrating mechanism (CCM) of C4 plants have not been well studied. Here, we estimated the temperature response of gm , gbs and leakiness (ϕ), the amount of concentrated CO2 that escapes the bundle-sheath cells, for the chilling-tolerant C4 plant Miscanthus × giganteus grown at 14 and 25°C. To estimate these parameters, we combined the C4 -enzyme-limited photosynthesis model and the Δ13 C discrimination model. These combined models were parameterised using in vitro activities of carbonic anhydrase (CA), pyruvate, phosphate dikinase (PPDK), ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), and phosphoenolpyruvate carboxylase (PEPc). Cold-grown Miscanthus plants increased in vitro activities of RuBisCO and PPDK but decreased PEPc activity compared with warm-grown plants. Mesophyll conductance and gbs responded strongly to measurement temperatures but did not differ between plants from the two growth temperatures. Furthermore, modelling showed that ϕ increased with measurement temperatures for both cold-grown and warm-grown plants, but was only marginally larger in cold-grown compared with warm-grown plants. Our results in Miscanthus support that gm and gbs are unresponsive to growth temperature and that the CCM is able to acclimate to cold through increased activity of PPDK and RuBisCO.

Quantitative proteomic analysis reveals high interference on protein expression of H9c2 cells activated with glucose and cardiotonic steroids.

In recent decades, the incidence of death and morbidity due to diabetes has increased worldwide, causing a high social and economic impact. Diabetes is a major cause of blindness, kidney failure, heart attack, stroke and lower limb amputation. However, the molecular mechanisms that make the heart and kidneys the main targets of diabetes are not completely understood. To better understand the complex biochemical mechanism of diabetic cardiomyopathy, we investigated the effects of hyperglycemia with concomitant digoxin and ouabain stimulation in H9c2 cells. Total extracted proteins were analyzed by label-free LC-MS/MS, quantified by Scaffold software and validated by parallel reaction monitoring (PRM) methodology. Here, we show that the eukaryotic initiation factors (Eifs) and elongation factors (Eefs) Eif3f, Eef2 and Eif4a1 are overexpressed following cardiotonic steroid (CTS) stimulation. Similarly, the expression of four 14-3-3 proteins that play a key role in cardiac ventricular compaction was altered after CTS stimulation. In total, the expression of nine protein groups was altered in response to the stimulation of H9c2 cells. Here, the biological consequences of these changes are discussed in depth. SIGNIFICANCE: Hyperglycemia is the main physiological condition that provokes tissue and vascular injuries in heart of diabetic patients. However, the changings at large scale in the expression of proteins of cardiomyocytes generated by this condition was not yet studied. Here we report for the first time the altered biosynthesis of nine groups of proteins of H9c2 cells activated by high glucose concentrations and by cardiotonic steroids (CTS). Furthermore, the increased biosynthesis of Eifs, Eefs and 14-3-3 protein groups by CTS, which play a crucial role in cardiomyopathies are original data reported in this work. These findings not only enhance our knowledge concerning to the effects of hyperglycemia and CTS on H9c2 cells but also indicate potential molecular targets to interfere in diabetes cardiomyopathy progression.

Direct Whole-Genome Sequencing of Sputum Accurately Identifies Drug-Resistant Mycobacterium tuberculosis Faster than MGIT Culture Sequencing.

The current methods available to diagnose antimicrobial-resistant Mycobacterium tuberculosis infections require a positive culture or only test a limited number of resistance-associated mutations. A rapid accurate identification of antimicrobial resistance enables the prompt initiation of effective treatment. Here, we determine the utility of whole-genome sequencing (WGS) of M. tuberculosis directly from routinely obtained diagnostic sputum samples to provide a comprehensive resistance profile compared to that from mycobacterial growth indicator tube (MGIT) WGS. We sequenced M. tuberculosis from 43 sputum samples by targeted DNA enrichment using the Agilent SureSelectXT kit, and 43 MGIT positive samples from each participant. Thirty two (74%) sputum samples and 43 (100%) MGIT samples generated whole genomes. The times to antimicrobial resistance profiles and concordance were compared with Xpert MTB/RIF and phenotypic resistance testing from cultures of the same samples. Antibiotic susceptibility could be predicted from WGS of sputum within 5 days of sample receipt and up to 24 days earlier than WGS from MGIT culture and up to 31 days earlier than phenotypic testing. Direct sputum results could be reduced to 3 days with faster hybridization and if only regions encoding drug resistance are sequenced. We show that direct sputum sequencing has the potential to provide comprehensive resistance detection significantly faster than MGIT whole-genome sequencing or phenotypic testing of resistance from cultures in a clinical setting. This improved turnaround time enables prompt appropriate treatment with associated patient and health service benefits. Improvements in sample preparation are necessary to ensure comparable sensitivities and complete resistance profile predictions in all cases.

Use of Whole-Genome Sequencing of Adenovirus in Immunocompromised Pediatric Patients to Identify Nosocomial Transmission and Mixed-Genotype Infection.

Background: Adenoviruses are significant pathogens for the immunocompromised, arising from primary infection or reinfection. Serotyping is insufficient to support nosocomial transmission investigations. We investigate whether whole-genome sequencing (WGS) provides clinically relevant information on transmission among patients in a pediatric tertiary hospital. Methods: We developed a target-enriched adenovirus WGS technique for clinical samples and retrospectively sequenced 107 adenovirus-positive residual diagnostic samples, including viremias (>5 × 104 copies/mL), from 37 patients collected January 2011-March 2016. Whole-genome sequencing was used to determine genotype and for phylogenetic analysis. Results: Adenovirus sequences were recovered from 105 of 107 samples. Full genome sequences were recovered from all 20 nonspecies C samples and from 36 of 85 species C viruses, with partial genome sequences recovered from the rest. Whole-genome phylogenetic analysis suggested linkage of 3 genotype A31 cases and uncovered an unsuspected epidemiological link to an A31 infection first detected on the same ward 4 years earlier. In 9 samples from 1 patient who died, we identified a mixed genotype adenovirus infection. Conclusions: Adenovirus WGS from clinical samples is possible and useful for genotyping and molecular epidemiology. Whole-genome sequencing identified likely nosocomial transmission with greater resolution than conventional genotyping and distinguished between adenovirus disease due to single or multiple genotypes.

Phragmoplast microtubule dynamics - a game of zones.

Plant morphogenesis relies on the accurate positioning of the partition (cell plate) between dividing cells during cytokinesis. The cell plate is synthetized by a specialized structure called the phragmoplast, which consists of microtubules, actin filaments, membrane compartments and associated proteins. The phragmoplast forms between daughter nuclei during the transition from anaphase to telophase. As cells are commonly larger than the originally formed phragmoplast, the construction of the cell plate requires phragmoplast expansion. This expansion depends on microtubule polymerization at the phragmoplast forefront (leading zone) and loss at the back (lagging zone). Leading and lagging zones sandwich the 'transition' zone. A population of stable microtubules in the transition zone facilitates transport of building materials to the midzone where the cell plate assembly takes place. Whereas microtubules undergo dynamic instability in all zones, the overall balance appears to be shifted towards depolymerization in the lagging zone. Polymerization of microtubules behind the lagging zone has not been reported to date, suggesting that microtubule loss there is irreversible. In this Review, we discuss: (1) the regulation of microtubule dynamics in the phragmoplast zones during expansion; (2) mechanisms of the midzone establishment and initiation of cell plate biogenesis; and (3) signaling in the phragmoplast.

Norovirus Whole-Genome Sequencing by SureSelect Target Enrichment: a Robust and Sensitive Method.

Norovirus full-genome sequencing is challenging due to sequence heterogeneity among genomes. Previous methods have relied on PCR amplification, which is problematic due to primer design, and transcriptome sequencing (RNA-Seq), which nonspecifically sequences all RNA, including host and bacterial RNA, in stool specimens. Target enrichment uses a panel of custom-designed 120-mer RNA baits that are complementary to all publicly available norovirus sequences, with multiple baits targeting each position of the genome, which overcomes the challenge of primer design. Norovirus genomes are enriched from stool RNA extracts to minimize the sequencing of nontarget RNA. SureSelect target enrichment and Illumina sequencing were used to sequence full genomes from 507 norovirus-positive stool samples with reverse transcription-real-time PCR cycle threshold (CT) values of 10 to 43. Sequencing on an Illumina MiSeq system in batches of 48 generated, on average, 81% on-target reads per sample and 100% genome coverage with >12,000-fold read depth. Samples included genotypes GI.1, GI.2, GI.3, GI.6, GI.7, GII.1, GII.2, GII.3, GII.4, GII.5, GII.6, GII.7, GII.13, GII.14, and GII.17. When outliers were accounted for, we generated >80% genome coverage for all positive samples, regardless of CT values. A total of 164 samples were tested in parallel with conventional PCR genotyping of the capsid shell domain; 164/164 samples were successfully sequenced, compared to 158/164 samples that were amplified by PCR. Four of the samples that failed capsid PCR analysis had low titers, which suggests that target enrichment is more sensitive than gel-based PCR. Two samples failed PCR due to primer mismatches; target enrichment uses multiple baits targeting each position, thus accommodating sequence heterogeneity among norovirus genomes.

Quantitative proteomic analysis of Huh-7 cells infected with Dengue virus by label-free LC-MS.

Dengue is an important and growing public health problem worldwide with an estimated 100million new clinical cases annually. Currently, no licensed drug or vaccine is available. During natural infection in humans, liver cells constitute one of the main targets of dengue virus (DENV) replication. However, a clear understanding of dengue pathogenesis remains elusive. In order to gain a better reading of the cross talk between virus and host cell proteins, we used a proteomics approach to analyze the host response to DENV infection in a hepatic cell line Huh-7. Differences in proteome expression were assayed 24h post-infection using label-free LC-MS. Quantitative analysis revealed 155 differentially expressed proteins, 64 of which were up-regulated and 91 down-regulated. These results reveal an important decrease in the expression of enzymes involved in the glycolytic pathway, citrate cycle, and pyruvate metabolism. This study provides large-scale quantitative information regarding protein expression in the early stages of infection that should be useful for better compression of the pathogenesis of dengue. BIOLOGICAL SIGNIFICANCE: Dengue infection involves alterations in the homeostasis of the host cell. Defining the interactions between virus and cell proteins should provide a better understanding of how viruses propagate and cause disease. Here, we present for the first time the proteomic analysis of hepatocytes (Huh-7 cells) infected with DENV-2 by label-free LC-MS.

[Open vacuum-pack abdomen. An ideal technique for deferred temporary abdominal closure in complications after cytoreduction surgery and intraperitoneal chemotherapy with hyperthermia due to peritoneal cancer]. / Open vacuum-pack, técnica ideal del cierre abdominal temporal diferido en las complicaciones tras cirugía citorreductora y quimioterapia intraperitoneal con hipertermia por carcinomatosis peritoneal.

INTRODUCTION: The use of a new therapeutic alternative involving cytoreductive surgery with perioperative intraperitoneal chemotherapy in the treatment of patients suffering from peritoneal carcinomatosis represents a new challenge for the multidisciplinary teams caring for these patients. Their post-operative progress and care needs, apart from differing from those of conventional patients, have not yet been completely defined or protocolised. In this presentation we explain the special characteristics of these patients compared to the usual surgical patients, the possible physiopathological mechanisms which may give rise to the different types of complications, the circumstances when a temporary abdominal closure is necessary, the ideal conditions required for an optimal technique, and finally our experience with the open vacuum abdomen technique in the treatment of the complications that appear in patients treated by this new triple combined therapy. PATIENTS AND METHODS: Based on our personal experience in the treatment of 110 cytoreductions carried out between February 1997 and February 2007 on 71 patients suffering from peritoneal carcinomatosis of various origins. Of the 71 patients, 50 (70%) suffered some kind of complication during their postoperative evolution, 28 of them requiring re-operation for a Grade III-IV postoperative complication. The abdominal situation made a temporary closure desirable in 17 patients, having applied an open vacuum abdomen technique on every occasion. We study this group of patients according their original type of tumour and stage of the disease at the cytoreductive procedure, peritonectomies and visceral resections required, type of postoperative complications, treatment applied and evolution. RESULTS: A total of 52 open vacuum abdomen procedures were required (median, 2.8 per patient; range, 1-10) before the abdominal complication could be completely kept under control in these 17 patients. Only 2 postoperative intestinal fistulas were directly related to this technique, and a primary closure of the whole abdominal wall was possible in 11 of these patients (66%). All but one of them left the hospital alive and well. CONCLUSIONS: As a consequence of this experience, in our opinion, the open vacuum abdomen is the ideal election technique to be employed in any temporary closure of the abdominal cavity for whatever reason it is required, including the worst possible surgical scenario, as we have demonstrated in the treatment of surgical complications after cytoreductive procedures and intraperitoneal chemohyperthermia.

Open vacuum-pack, técnica ideal del cierre abdominal temporal diferido en las complicaciones tras cirugía citorreductora y quimioterapia intraperitoneal con hipertermia por carcinomatosis peritoneal / Open vacuum-pack abdomen. An ideal technique for deferred temporary abdominal closure in complications after cytoreduction surgery and intraperitoneal chemotherapy with hyperthermia due to peritoneal cancer

Introducción. La utilización de una nueva alternativa terapéutica en pacientes afectos de carcinomatosis peritoneal mediante la aplicación de cirugía citorreductora radical oncológica, junto con la administración de quimioterapia intraperitoneal perioperatoria, supone un nuevo reto para los equipos multidisciplinarios que están al cuidado de estos pacientes, por cuanto su evolución postoperatoria y requerimientos de cuidados además de ser distintos de los de los pacientes convencionales, no están totalmente definidos ni protocolizados. El objetivo del presente trabajo es exponer nuestra experiencia con la aplicación del abdomen abierto en vacío, como técnica de cierre abdominal diferido, en el tratamiento de las complicaciones aparecidas en los pacientes sometidos a esta nueva triple terapia combinada. Material y método. Nos hemos basado en nuestra experiencia personal en el tratamiento de 110 citorreducciones realizadas entre febrero de 1997 y febrero de 2007 en 71 pacientes afectos de carcinomatosis peritoneal difusa de diferente origen. De los 71 pacientes, 50 (70%) sufrieron algún tipo de complicación durante su evolución postoperatoria, 28 de estos pacientes precisaron alguna reintervención por complicaciones de grado III-IV. La situación abdominal hizo aconsejable un cierre abdominal diferido en 17 pacientes, en todas las ocasiones se practicó la técnica de abdomen abierto en vacío. Se estudia esta serie de pacientes en cuanto al tipo de tumor original y grado de enfermedad en el momento de la citorreducción, peritonectomías parietales y resecciones viscerales necesarias, tipo y momento de aparición de complicación, tratamiento aplicado y evolución. Resultados. Fue necesario un total de 52 abdómenes en vacío (mediana, 2,8 por paciente; intervalo, 1-10) antes de que la complicación abdominal estuviera completamente bajo control en estos 17 pacientes. Hemos observado solamente 2 fístulas intestinales relacionadas directamente con esta técnica, y en 11 (66%) de estos pacientes fue posible un cierre primario de toda la pared abdominal. Todos los pacientes, salvo uno, abandonaron el hospital vivos y con buen estado general. Conclusiones. Como consecuencia de esta experiencia, en nuestra opinión, el abdomen abierto en vacío es la técnica de elección para cualquier cierre temporal de la cavidad abdominal independientemente de la razón por la que se precise, incluso en el peor de los escenarios posibles, como hemos demostrado en el tratamiento de las complicaciones quirúrgicas tras citorreducciones y quimiohipertermia intraperitoneal (AU)

Introduction. The use of a new therapeutic alternative involving cytoreductive surgery with perioperative intraperitoneal chemotherapy in the treatment of patients suffering from peritoneal carcinomatosis represents a new challenge for the multidisciplinary teams caring for these patients. Their post-operative progress and care needs, apart from differing from those of conventional patients, have not yet been completely defined or protocolised. In this presentation we explain the special characteristics of these patients compared to the usual surgical patients, the possible physiopathological mechanisms which may give rise to the different types of complications, the circumstances when a temporary abdominal closure is necessary, the ideal conditions required for an optimal technique, and finally our experience with the open vacuum abdomen technique in the treatment of the complications that appear in patients treated by this new triple combined therapy. Patients and methods. Based on our personal experience in the treatment of 110 cytoreductions carried out between February 1997 and February 2007 on 71 patients suffering from peritoneal carcinomatosis of various origins. Of the 71 patients, 50 (70%) suffered some kind of complication during their postoperative evolution, 28 of them requiring re-operation for a Grade III-IV postoperative complication. The abdominal situation made a temporary closure desirable in 17 patients, having applied an open vacuum abdomen technique on every occasion. We study this group of patients according their original type of tumour and stage of the disease at the cytoreductive procedure, peritonectomies and visceral resections required, type of postoperative complications, treatment applied and evolution. Results. A total of 52 open vacuum abdomen procedures were required (median, 2.8 per patient; range, 1-10) before the abdominal complication could be completely kept under control in these 17 patients. Only 2 postoperative intestinal fistulas were directly related to this technique, and a primary closure of the whole abdominal wall was possible in 11 of these patients (66%). All but one of them left the hospital alive and well. Conclusions. As a consequence of this experience, in our opinion, the open vacuum abdomen is the ideal election technique to be employed in any temporary closure of the abdominal cavity for whatever reason it is required, including the worst possible surgical scenario, as we have demonstrated in the treatment of surgical complications after cytoreductive procedures and intraperitoneal chemohyperthermia (AU)

Lesión iatrogénica del conducto sectorial anterior derecho hepático (segmentos V-VIII) aberrante e independiente. Dificultades en su diagnóstico y tratamiento / Iatrogenic injury of the independently abnormal, right anterior hepatic sectorial (segments V-VIII) canal. Difficulties in its diagnosis and treatment

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[Malignant peritoneal mesothelioma. Our experienced with triple combined therapy: cytoreduction, intraperitoneal perioperative chemotherapy and hyperthermia]. / Mesotelioma peritoneal maligno. Nuestra experiencia con la triple terapia combinada: citorreducción, quimioterapia intraperitoneal perioperatoria e hipertermia.

INTRODUCTION: Malignant peritoneal mesothelioma is the most common primary neoplasm of the serous peritoneum. Most patients die of the complications of local disease confined to the peritoneal cavity, while nodal or distant dissemination is extremely rare. Prognosis with traditional therapeutic options is dismal, with a median survival of between 4 and 12 months from diagnosis. The application of a new combined therapy with cytoreductive surgery, intraperitoneal perioperative chemotherapy and heated intraperitoneal intraoperative chemotherapy, followed by early postoperative intraperitoneal chemotherapy is currently providing good results, in some instances even allowing curative intent. We present a series of patients treated with this triple combined therapy. MATERIAL AND METHOD: Between December 1998 and December 2005, 78 cytoreductive surgeries were performed in 50 patients in our peritoneal carcinomatosis program at the San Jose Policlinic in Vitoria (Spain), for distinct reasons. Among these patients, surgery was performed on 11 occasions in seven patients with a diffuse malignant peritoneal mesothelioma. The present study focuses on this latter group of seven patients. RESULTS: Eleven cytoreductions were performed in seven patients with diffuse malignant peritoneal mesothelioma. There were four men and three women, with a mean age of 50 years (range 31-57 years). None of the patients had a history of occupational exposure to asbestos or contact with this substance. All the patients had received more than one surgical intervention before entering our program. Only two patients had also received systemic chemotherapy as adjuvant treatment after their initial diagnosis, as the only possible therapeutic alternative. Treatment with curative intent was provided, obtaining complete cytoreduction of macroscopic disease in all patients, followed by application of intraperitoneal perioperative chemotherapy for the treatment of any residual microscopic disease. Pathologic analysis showed biphasic sarcomatous mesothelioma in two patients and epithelial mesothelioma in the remaining five patients. Postoperative complications occurred in five patients, resulting in a mean length of postoperative hospital stay of 41.5 days (range 17-84 days). Three patients died from disease progression at 3, 9 and 11 months after the initial cytoreduction; of these, two patients had diffuse biphasic sarcomatous mesothelioma. The remaining four patients are still alive at 5, 9, 19 and 54 months after the initial cytoreduction without evidence of disease at the present time. CONCLUSIONS: Radical oncologic cytoreductive surgery combined with intraperitoneal perioperative chemotherapy provides good results with prolonged survival in selected cases, although morbidity is high. Based in our experience, biphasic sarcomatous mesotheliomas should be excluded from this protocol because of their aggressiveness; these tumors should be included only in conventional therapeutic strategies with palliative intent.

Mesotelioma peritoneal maligno. Nuestra experiencia con la triple terapia combinada: citorreducción, quimioterapia intraperitoneal perioperatoria e hipertermia / Malignant peritoneal mesothelioma. Our experienced with triple combined therapy: cytoreduction, intraperitoneal perioperative chemotherapy and hyperthermia

Introducción. El mesotelioma peritoneal maligno es la neoplasia primaria más común de la serosa peritoneal. Presenta un alto grado de agresividad local y es rara su diseminación ganglionar y/o a distancia. Su pronóstico con el enfoque de tratamiento tradicional es nefasto, con medianas de supervivencia de 4 a 12 meses. La aplicación de una nueva terapia combinada de cirugía citorreductora junto con quimioterapia intraperitoneal perioperatoria, quimioterapia intraperitoneal intraoperatoria hipertérmica (QIIH), seguida de quimioterapia intraperitoneal postoperatoria precoz (QIPP), está posibilitando buenos resultados, incluso en ocasiones con intención curativa. Se presenta nuestra serie personal tratada con esta triple terapia combinada. Material y método. Entre diciembre de 1998 y diciembre de 2005, en nuestro Programa de Carcinomatosis Peritoneal de la Policlínica San José de Vitoria, se han realizado 78 citorreducciones en 50 pacientes de diverso origen, de las que en 11 ocasiones en 7 pacientes se trataba de mesotelioma peritoneal difuso primario maligno como causa de la enfermedad. Se estudia a este grupo de pacientes. Resultados. Se han realizado 11 citorreducciones en 7 pacientes por mesotelioma peritoneal difuso primario maligno, 4 pacientes varones y 3 mujeres, con edad media de 50 (intervalo, 31-57) años. Ninguno tenía antecedentes laborales ni de contacto con asbesto. Todos ellos habían recibido más de una cirugía previa antes de venir a nuestro programa, mientras que solamente 2 pacientes también habían recibido quimioterapia sistémica como tratamiento adyuvante tras diagnóstico de confirmación como única alternativa terapéutica posible. Se realizó un tratamiento con intención curativa, y en todos los casos se consiguió una citorreducción completa de la enfermedad macroscópica, seguida de la aplicación de quimioterapia intraperitoneal perioperatoria para el tratamiento de la enfermedad microscópica residual si la hubiere. La anatomía patológica demostró un mesotelioma bifásico sarcomatoso en 2 ocasiones y un mesotelioma epitelial en los otros 5 pacientes; 5 pacientes presentaron algún tipo de complicación postoperatoria, lo que justifica una estancia media hospitalaria de 41,5 (17-84) días. Han fallecido 3 pacientes por progresión de la enfermedad a los 3, 9 y 11 meses de su citorreducción inicial, 2 de ellos por mesotelioma difuso bifásico sarcomatoso. Los otros 4 pacientes permanecen vivos a los 5, 9, 19 y 54 meses de su primera citorreducción, sin evidencia de enfermedad en la actualidad. Conclusiones. La cirugía citorreductora radical oncológica combinada con la aplicación intraperitoneal perioperatoria de quimioterapia presenta buenos resultados, con supervivencias prolongadas en casos seleccionados, si bien conlleva una elevada morbilidad. En nuestra experiencia, los mesoteliomas bifásicos sarcomatosos deberían excluirse de este protocolo por lo agresivo de la enfermedad e incluirse únicamente en esquemas terapéuticos convencionales con intención paliativa (AU)

Introduction. Malignant peritoneal mesothelioma is the most common primary neoplasm of the serous peritoneum. Most patients die of the complications of local disease confined to the peritoneal cavity, while nodal or distant dissemination is extremely rare. Prognosis with traditional therapeutic options is dismal, with a median survival of between 4 and 12 months from diagnosis. The application of a new combined therapy with cytoreductive surgery, intraperitoneal perioperative chemotherapy and heated intraperitoneal intraoperative chemotherapy, followed by early postoperative intraperitoneal chemotherapy is currently providing good results, in some instances even allowing curative intent. We present a series of patients treated with this triple combined therapy. Material and method. Between December 1998 and December 2005, 78 cytoreductive surgeries were performed in 50 patients in our peritoneal carcinomatosis program at the San Jose Policlinic in Vitoria (Spain), for distinct reasons. Among these patients, surgery was performed on 11 occasions in seven patients with a diffuse malignant peritoneal mesothelioma. The present study focuses on this latter group of seven patients. Results. Eleven cytoreductions were performed in seven patients with diffuse malignant peritoneal mesothelioma. There were four men and three women, with a mean age of 50 years (range 31-57 years). None of the patients had a history of occupational exposure to asbestos or contact with this substance. All the patients had received more than one surgical intervention before entering our program. Only two patients had also received systemic chemotherapy as adjuvant treatment after their initial diagnosis, as the only possible therapeutic alternative. Treatment with curative intent was provided, obtaining complete cytoreduction of macroscopic disease in all patients, followed by application of intraperitoneal perioperative chemotherapy for the treatment of any residual microscopic disease. Pathologic analysis showed biphasic sarcomatous mesothelioma in two patients and epithelial mesothelioma in the remaining five patients. Postoperative complications occurred in five patients, resulting in a mean length of postoperative hospital stay of 41.5 days (range 17-84 days). Three patients died from disease progression at 3, 9 and 11 months after the initial cytoreduction; of these, two patients had diffuse biphasic sarcomatous mesothelioma. The remaining four patients are still alive at 5, 9, 19 and 54 months after the initial cytoreduction without evidence of disease at the present time. Conclusions. Radical oncologic cytoreductive surgery combined with intraperitoneal perioperative chemotherapy provides good results with prolonged survival in selected cases, although morbidity is high. Based in our experience, biphasic sarcomatous mesotheliomas should be excluded from this protocol because of their aggressiveness; these tumors should be included only in conventional therapeutic strategies with palliative intent (AU)