Immunological Cross-Reactivity and Preclinical Assessment of a Colombian Anticoral Antivenom against the Venoms of Three Micrurus Species.

Snakebite accident treatment requires the administration of antivenoms that provide efficacy and effectiveness against several snake venoms of the same genus or family. The low number of immunogenic components in venom mixtures that allow the production of antivenoms consequently gives them partial neutralization and a suboptimal pharmacological response. This study evaluates the immunorecognition and neutralizing efficacy of the polyvalent anticoral antivenom from the Instituto Nacional de Salud (INS) of Colombia against the heterologous endemic venoms of Micrurus medemi, and M. sangilensis, and M. helleri by assessing immunoreactivity through affinity chromatography, ELISA, Western blot, and neutralization capability. Immunorecognition towards the venoms of M. medemi and M. sangilensis showed values of 62% and 68% of the protein composition according to the immunoaffinity matrix, respectively. The analysis by Western blot depicted the highest recognition patterns for M. medemi, followed by M. sangilensis, and finally by M. helleri. These findings suggest that the venom compositions are closely related and exhibit similar recognition by the antivenom. According to enzyme immunoassays, M. helleri requires a higher amount of antivenom to achieve recognition than the others. Besides reinforcing the evaluation of INS antivenom capability, this work recommends the use of M. helleri in the production of Colombian antisera.

Unveiling the Venom Composition of the Colombian Coral Snakes Micrurus helleri, M. medemi, and M. sangilensis.

Little is known of the biochemical composition and functional features of the venoms of poorly known Colombian coral snakes. Here, we provide a preliminary characterization of the venom of two Colombian endemic coral snake species, Micrurus medemi and M. sangilensis, as well as Colombian populations of M. helleri. Electrophoresis and RP-HPLC techniques were used to identify venom components, and assays were conducted to detect enzyme activities, including phospholipase A2, hyaluronidase, and protease activities. The median lethal dose was determined using murine models. Cytotoxic activities in primary cultures from hippocampal neurons and cancer cell lines were evaluated. The venom profiles revealed similarities in electrophoretic separation among proteins under 20 kDa. The differences in chromatographic profiles were significant, mainly between the fractions containing medium-/large-sized and hydrophobic proteins; this was corroborated by a proteomic analysis which showed the expected composition of neurotoxins from the PLA2 (~38%) and 3FTx (~17%) families; however, a considerable quantity of metalloproteinases (~12%) was detected. PLA2 activity and protease activity were higher in M. helleri venom according to qualitative and quantitative assays. M. medemi venom had the highest lethality. All venoms decreased cell viability when tested on tumoral cell cultures, and M. helleri venom had the highest activity in neuronal primary culture. These preliminary studies shed light on the venoms of understudied coral snakes and broaden the range of sources that could be used for subsequent investigations of components with applications to specific diseases. Our findings also have implications for the clinical manifestations of snake envenoming and improvements in its medical management.

Intraspecific Differences in the Venom of Crotalus durissus cumanensis from Colombia.

Biochemical and biological differences in the venom of Crotalus durissus cumanensis from three ecoregions of Colombia were evaluated. Rattlesnakes were collected from the geographic areas of Magdalena Medio (MM), Caribe (CA) and Orinoquía (OR). All three regionally distributed venoms contain proteases, PLA2s and the basic subunit of crotoxin. However, only crotamine was detected in the CA venom. The highest lethality, coagulant, phospholipase A2 and hyaluronidase activities were found in the MM venom. Also, some differences, observed by western blot and immunoaffinity, were found in all three venoms when using commercial antivenoms. Furthermore, all three eco-regional venoms showed intraspecific variability, considering the differences in the abundance and intensity of their components, in addition to the activity and response to commercial antivenoms.

Safety of endoscopist-administered deep sedation with propofol in ASA III patients

Introduction: deep sedation controlled by the endoscopist is safe in patients with low anesthetic risk (ASA I-II). However, scarce evidence is available in patients with intermediate risk (ASA III).Objective: to evaluate the safety of deep sedation with propofol controlled by the usual endoscopy staff (endoscopist, nurse, assistant) in outpatients classified as ASA III and the risk factors for the occurrence of complications during deep sedation.Patients and methods: this observational and single-center cross-sectional study included consecutive patients undergoing non-complex procedures in which deep sedation was administered by the endoscopy staff. Patients were divided into group I (ASA = III) and group II (ASA < III).Results: a total of 562 patients were included and 80 (14.2 %) were in group I. Complications related to deep sedation were more frequent in group I (23.8 % vs 14.5 %; p = 0.036), mainly mild desaturations (13.8 % vs 7.5 %; p = 0.058). Emergency intervention or death were not registered. The adjusted analysis identified age as the only independent baseline risk factor for developing global adverse events.Conclusion: ASA III patients developed more sedation-related complications than ASA I-II patients. However, these complications were mild and did not prevent the correct performance of the procedure. (AU)

Safety of endoscopist-administered deep sedation with propofol in ASA III patients.

INTRODUCTION: deep sedation controlled by the endoscopist is safe in patients with low anesthetic risk (ASA I-II). However, scarce evidence is available in patients with intermediate risk (ASA III). OBJECTIVE: to evaluate the safety of deep sedation with propofol controlled by the usual endoscopy staff (endoscopist, nurse, assistant) in outpatients classified as ASA III and the risk factors for the occurrence of complications during deep sedation. PATIENTS AND METHODS: this observational and single-center cross-sectional study included consecutive patients undergoing non-complex procedures in which deep sedation was administered by the endoscopy staff. Patients were divided into group I (ASA = III) and group II (ASA < III). RESULTS: a total of 562 patients were included and 80 (14.2 %) were in group I. Complications related to deep sedation were more frequent in group I (23.8 % vs 14.5 %; p = 0.036), mainly mild desaturations (13.8 % vs 7.5 %; p = 0.058). Emergency intervention or death were not registered. The adjusted analysis identified age as the only independent baseline risk factor for developing global adverse events. CONCLUSION: ASA III patients developed more sedation-related complications than ASA I-II patients. However, these complications were mild and did not prevent the correct performance of the procedure.

Effect and Response of Quercus ilex subsp. ballota [Desf.] Samp. Seedlings From Three Contrasting Andalusian Populations to Individual and Combined Phytophthora cinnamomi and Drought Stresses.

Quercus ilex L. is the dominant species in the Mediterranean forest and agrosilvopastoral ecosystem "dehesa." Currently, this forest species is threatened by natural and anthropogenic agents, especially by the decline syndrome, which is caused by Phytophthora cinnamomi and drought periods. Although the morphological and physiological responses of Q. ilex to combined stress (P. cinnamomi and drought) have been examined already, little is known at the molecular level. In this study, we studied the effect and response of 8-month seedlings from three contrasting Andalusian populations (Seville [Se], Granada [Gr], and Almeria [Al]) to the individual and combined stresses of P. cinnamomi and drought from morphological, physiological, biochemical, and proteomics data. Whereas, seedling damage (leaf chlorosis and necrosis) and mortality were greater under the combined stresses in the three populations, the effect of each individual stress was population-dependent. Resilient individuals were found in all the populations at different percentages. The decrease in leaf chlorophyll fluorescence, photosynthetic activity, and stomatal conductance observed in undamaged seedlings was greater in the presence of both stresses, the three populations responding similarly to drought and P. cinnamomi. Biochemical and proteomic analyses of undamaged seedlings from the two most markedly contrasting populations (Se and Al) revealed the absence of significant differences in the contents in photosynthetic pigments, amino acids, and phenolics among treatments. The Se and Al populations exhibited changes in protein profile in response to the different treatments, with 83 variable proteins in the former population and 223 in the latter. Variable proteins belonged to 16 different functional groups, the best represented among which were protein folding, sorting and degradation, carbohydrate, amino acid, and secondary metabolism, photosynthesis, and ROS scavenging. While photosynthetic proteins were mainly downaccumulated, those of stress-responsive were upaccumulated. Although no treatment-specific response was observed in any functional group, differences in abundance were especially marked under the combined stresses. The following variable proteins are proposed as putative markers for resilience in Q. ilex, namely, aldehyde dehydrogenase, glucose-6-phosphate isomerase, 50S ribosomal protein L5, and α-1,4-glucan-protein synthase [UDP-forming].

Effects of Somatic Methylation in Colonic Polyps on Risk of Developing Metachronous Advanced Colorectal Lesions.

The utility of molecular markers for predicting the risk of metachronous advanced colorectal lesions (MACLs) remains poorly investigated. We examined the relationship between somatic hypermethylation in polyps at baseline and the risk of developing MACL. This retrospective cohort study included 281 consecutive patients with colonic polyps who were enrolled between 2007 and 2009 and followed-up until 2014. MACLs were defined as adenomas of ≥10 mm, high-grade dysplasia, or with a villous component; and serrated lesions of ≥10 mm or with dysplasia. In total, 595 polyps were removed at baseline colonoscopy and analyzed for pathological characteristics and CpG island methylator phenotype (CIMP) using the MS-MLPA (Methylation-Specific -- Multiplex Ligation-dependent Probe Amplification) technique. Forty-five patients (16.0%) showed at least one CIMP+ polyp. MACL risk was higher in patients with CIMP+ polyps (odds ratio (OR), 4.50; 95% CI, 1.78-11.4; p = 0.002). Patients with CIMP+ polyps also exhibited shorter time to MACL development (33.8 months vs. 50.1 months; p < 0.001), even with adjustment for polyp size and number (OR, 2.40; 95% CI, 1.33-4.34). Adding CIMP analysis improved the sensitivity (57.0% to 70.9%), negative predictive value (71.1% to 77.3%), and overall accuracy (49.8% to 52.0%) for MACL risk estimation. These results highlight that CIMP may be a useful marker for endoscopic surveillance.

Diagnostic yield of early repeat colonoscopy after suboptimal bowel preparation in a fecal immunochemical test-based screening program.

BACKGROUND: Current guidelines regarding surveillance after screening colonoscopy assume adequate bowel preparation. However, follow-up intervals after suboptimal cleansing are highly heterogeneous. We aimed to determine the diagnostic yield of early repeat colonoscopy in patients with suboptimal bowel preparation in fecal immunochemical test (FIT)-based screening colonoscopy. METHODS: An observational study including patients who underwent colonoscopy with suboptimal bowel preparation after positive FIT screening and then repeat colonoscopy within 1 year. Suboptimal preparation was defined as a Boston Bowel Preparation Scale (BBPS) score of 1 in any segment. Patients with a BBPS score of 0 in any segment or incomplete examination were excluded. The adenoma detection rate (ADR), advanced ADR (AADR), and colorectal cancer rate were calculated for the index and repeat colonoscopies. RESULTS: Of the 2474 patients with FIT-positive colonoscopy at our center during this period, 314 (12.7 %) had suboptimal preparation. Of the 259 (82.5 %) patients who underwent repeat colonoscopy, suboptimal cleansing persisted in 22 (9 %). On repeat colonoscopy, the ADR was 38.7 % (95 %CI 32.6 % to 44.8 %) and the AADR was 14.9 % (95 %CI 10.5 % to 19.4 %). The per-adenoma miss rate was 27.7 % (95 %CI 24.0 % to 31.6 %), and the per-advanced adenoma miss rate was 17.6 % (95 %CI 13.3 % to 22.7 %). After repeat colonoscopy, the post-polypectomy surveillance recommendation changed from 10 to 3 years in 14.7 % of the patients with previous 10-year surveillance recommendation. CONCLUSIONS: Patients with suboptimal bowel preparation on FIT-positive colonoscopy present a high rate of advanced adenomas in repeat colonoscopy, with major changes in post-polypectomy surveillance recommendations.

Síndrome de Li-Fraumeni / Li Fraumeni síndrome

No disponible

Assessment of functional and structural changes of soil fungal and oomycete communities in holm oak declined dehesas through metabarcoding analysis.

Forest decline is nowadays a major challenge for ecosystem sustainability. Dehesas, which consists of savannah-like mediterranean ecosystems, are threatened by the holm oak decline in the south-west of Iberian Peninsula. Phytophthora cinnamomi is considered the main agent of holm oak root rot, but little is known about the relationship between diversity of soilborne microbial community and the decline syndrome of holm oak. It would be hypothesized that the changes in the structure and functionality of the soil microbiome might influence tree health status through changes in richness and diversity of beneficial organisms such as mycorrhizal species, or fungal plant pathogens such as Fusarium spp. or Alternaria spp. Total DNA of soil samples from declined oak dehesas was extracted and analyzed through metabarcoding techniques, to evaluate the specific composition and diversity of the fungal and oomycete communities and their relationship with the disease symptoms. The fungal community included a wide range of pathogens and abundance of ectomycorrhizal key taxa related with low defoliation degree. Phytophthora cinnamomi and Pythium spiculum did not appear among the most abundant oomycetes, nor were they related directly to defoliation levels. Moreover, a particular taxon belonging to the genus Trichoderma was strongly correlated with the scarcity of pathogenic Phytophthora spp. The diversity and composition of fungal and oomycete communities were related to the severity of the decline symptoms. The metabarcoding study of microbiome represents a powerful tool to develop biocontrol strategies for the management of the holm oak root rot.

A polyvalent coral snake antivenom with broad neutralization capacity.

Coral snakes of the genus Micrurus have a high diversity and wide distribution in the Americas. Despite envenomings by these animals being uncommon, accidents are often severe and may result in death. Producing an antivenom to treat these envenomings has been challenging since coral snakes are difficult to catch, produce small amounts of venom, and the antivenoms produced have shown limited cross neutralization. Here we present data of cross neutralization among monovalent antivenoms raised against M. dumerilii, M. isozonus, M. mipartitus and M. surinamensis and the development of a new polyvalent coral snake antivenom, resulting from the mix of monovalent antivenoms. Our results, show that this coral snake antivenom has high neutralizing potency and wide taxonomic coverage, constituting a possible alternative for a long sought Pan-American coral snake antivenom.

A method to quantify infection and colonization of holm oak (Quercus ilex) roots by Phytophthora cinnamomi.

Phytophthora cinnamomi Rands. is an important root rot pathogen widely distributed in the north hemisphere, with a large host range. Among others diseases, it is known to be a principal factor in the decline of holm oak and cork oak, the most important tree species in the "dehesa" ecosystem of south-western Spain. Previously, the focus of studies on P. cinnamomi and holm oak have been on molecular tools for identification, functional responses of the host, together with other physiological and morphological host variables. However, a microscopic index to describe the degree of infection and colonization in the plant tissues has not yet been developed. A colonization or infection index would be a useful tool for studies that examine differences between individuals subjected to different treatments or to individuals belonging to different breeding accessions, together with their specific responses to the pathogen. This work presents a methodology based on the capture and digital treatment of microscopic images, using simple and accessible software, together with a range of variables that quantify the infection and colonization process.

Ambispective comparative study of two surgical strategies for liver hydatidosis.

AIM: To investigate the morbidity, mortality, recurrence and technical aspects of two distinct surgical strategies that were implemented in successive periods. METHODS: Ninty-two patients with 113 cysts underwent surgical procedures. The study was divided into 2 periods. Data from first period (P1) were compiled retrospectively. The surgical strategy was conservative surgery. The second period (P2) included a prospective study conducted according to a protocol following the criterion that radical procedures should be performed whenever it is technically feasible. RESULTS: Patients of both periods showed no statistically significant differences in age, gender, cyst location or mortality. Among the P2 group, patients exhibited more preoperative jaundice, and cyst size was smaller (P < 0.05). Changes in surgical strategy increased the rate of radical surgery, decreases morbidity and in-hospital stay (P < 0.001). A negative result in P2 was the death of two old patients (4.8%) who had undergone conservative treatments. The rate of radical surgery in P2 was around 75%. CONCLUSION: Radical surgery should be the technique of choice whenever it is feasible, because it diminishes morbidity and in-hospital stay. Conservative surgery must be employed only in selected cases.

Lesiones iatrogénicas de la vía biliar / Latrogenic bile duct injuries

Las lesiones de la vía biliar se pueden producir por múltiples causas, siendo las lesiones iatrogénicas de la vía biliar las más frecuentes. Son situaciones clínicas complejas producidas en pacientes aparentemente sanos que se asocian a una morbilidad importante y una mortalidad baja pero no despreciable. Un tratamiento correcto requiere un alto nivel de sospecha en el intraoperatorio y en el postoperatorio inmediato, y un abordaje multidisciplinario entre cirujanos, radiólogos y endoscopistas para ofrecer al paciente el mejor diagnóstico inicial, las mejores opciones terapéuticas y el mejor manejo y seguimiento de las complicaciones. Con esta revisión pretendemos describir la situación actual de la literatura con respecto a este tipo de lesiones y su manejo terapéutico, y hemos efectuado un algoritmo terapéutico (AU)

Bile duct injuries can be caused by different reasons, with Iatrogenic Bile Duct Injuries (IBDI) being the most common factor. IBDI is a complex situation produced in apparently healthy patients and is associated with a high rate of morbidity and a low rate of mortality. A multidisciplinary approach between surgeons, radiologist and endoscopist offers the best chances for an initial diagnosis, therapeutic options, management and follow up of complications for the patient. The aim of this review is to describe the current medical literature with reference to IBDI, and discuss our therapeutic algorithm (AU)

[Iatrogenic bile duct injuries]. / Lesiones iatrogénicas de la vía biliar.

Bile duct injuries can be caused by different reasons, with Iatrogenic Bile Duct Injuries (IBDI) being the most common factor. IBDI is a complex situation produced in apparently healthy patients and is associated with a high rate of morbidity and a low rate of mortality. A multidisciplinary approach between surgeons, radiologist and endoscopist offers the best chances for an initial diagnosis, therapeutic options, management and follow up of complications for the patient. The aim of this review is to describe the current medical literature with reference to IBDI, and discuss our therapeutic algorithm.

[Intraoperative therapeutic intensification techniques in locally advanced abdominal sarcomas]. / Intensificación terapéutica intraoperatoria en el tratamiento de los sarcomas abdominales localmente avanzados.

INTRODUCTION: Sarcomas are rare tumors that develop from mesenchymal cells. Their management is difficult due to their changing histology, location, and behavior. In this article, we discuss the use of two intraoperative therapeutic intensification techniques, intraoperative radiotherapy (IORT) and hyperthermic intraoperative intraperitoneal chemotherapy (HIIC), in the treatment of locally advanced abdominal sarcomas and peritoneal sarcomatosis. MATERIAL AND METHODS: We analyzed a series of 20 consecutive patients diagnosed with advanced abdominal sarcoma and 5 patients with a diagnosis of peritoneal sarcomatosis who were evaluated and treated in our department from December 1996 to October 2005. In advanced abdominal sarcoma, we performed complete or maximal resection followed by IORT. In peritoneal sarcomatosis we performed massive cytoreduction followed by HIIC. RESULTS: The survival rate in advanced abdominal sarcomas without sarcomatosis was 65% at 26 months. Among the 5 patients diagnosed with peritoneal sarcomatosis, 3 were alive, and 2 were without recurrence at 20 months of follow-up. CONCLUSIONS: IORT associated with radical surgery seems to improve local control and survival in advanced abdominal sarcomas. Maximal cytoreduction plus HIIC used as treatment of peritoneal sarcomatosis is a feasible technique that offers a therapeutic option with curative intent.

Intensificación terapéutica intraoperatoria en el tratamiento de los sarcomas abdominales localmente avanzados / Intraoperative therapeutic intensification techniques in locally advanced abdominal sarcomas

Introducción. Los sarcomas son tumores infrecuentes que se desarrollan a partir de células mesenquimales. Su estudio y tratamiento es difícil debido a una histopatología, localización y comportamiento variables. En este artículo estudiamos el papel de las técnicas de intensificación terapéutica intraoperatoria: radioterapia intraoperatoria (RIO) y quimioterapia intraperitoneal intraoperatoria hipertérmica (QIOH), en el tratamiento de los sarcomas abdominales localmente avanzados y la sarcomatosis peritoneal. Material y métodos. Analizamos una serie de 20 pacientes consecutivos diagnosticados de sarcoma abdominal avanzado y 5 diagnosticados de sarcomatosis peritoneal, evaluados y tratados en nuestro servicio entre diciembre de 1996 y octubre de 2005. En el sarcoma localmente avanzado se realizó resección completa o máxima asociada a RIO. En sarcomatosis peritoneal se llevó a cabo la máxima citorreducción asociada a QIOH. Resultados. La tasa de supervivencia de los sarcomas abdominales avanzados sin sarcomatosis fue del 65% a los 26 meses. De los 5 pacientes con sarcomatosis peritoneal, 3 estaban vivos y 2 de ellos libres de enfermedad a los 20 meses de seguimiento. Conclusiones. La RIO asociada a cirugía radical parece mejorar el control local y la supervivencia en sarcomas abdominales avanzados. La citorreducción máxima más QIOH usada como tratamiento de la sarcomatosis peritoneal es una técnica factible y que ofrece una opción terapéutica con intención curativa (AU)

Introduction. Sarcomas are rare tumors that develop from mesenchymal cells. Their management is difficult due to their changing histology, location, and behavior. In this article, we discuss the use of two intraoperative therapeutic intensification techniques, intraoperative radiotherapy (IORT) and hyperthermic intraoperative intraperitoneal chemotherapy (HIIC), in the treatment of locally advanced abdominal sarcomas and peritoneal sarcomatosis. Material and methods. We analyzed a series of 20 consecutive patients diagnosed with advanced abdominal sarcoma and 5 patients with a diagnosis of peritoneal sarcomatosis who were evaluated and treated in our department from December 1996 to October 2005. In advanced abdominal sarcoma, we performed complete or maximal resection followed by IORT. In peritoneal sarcomatosis we performed massive cytoreduction followed by HIIC. Results. The survival rate in advanced abdominal sarcomas without sarcomatosis was 65% at 26 months. Among the 5 patients diagnosed with peritoneal sarcomatosis, 3 were alive, and 2 were without recurrence at 20 months of follow-up. Conclusions. IORT associated with radical surgery seems to improve local control and survival in advanced abdominal sarcomas. Maximal cytoreduction plus HIIC used as treatment of peritoneal sarcomatosis is a feasible technique that offers a therapeutic option with curative intent (AU)