Subtotal laparoscopic cholecystectomy versus conversion to open as a bailout procedure: a cohort study.

BACKGROUND: The aim of this study is to evaluate morbidity and mortality in patients taken to conversion to open procedure (CO) and subtotal laparoscopic cholecystectomy (SLC) as bailout procedures when performing difficult laparoscopic cholecystectomy. METHOD: This observational cohort study retrospectively analyzed patients taken to SLC or CO as bailout surgery during difficult laparoscopic cholecystectomy between 2014 and 2022. Univariable and multivariable logistic regression models were used to identify prognostic factors for morbimortality. RESULTS: A total of 675 patients were included. Of the 675 patients (mean [SD] age 63.85 ± 16.00 years; 390 [57.7%] male) included in the analysis, 452 (67%) underwent CO and 223 (33%) underwent SLC. Overall, neither procedure had an increased risk of major complications (89 [19.69%] vs 35 [15.69%] P.207). However, CO had an increased risk of bile duct injury (18 [3.98] vs 1 [0.44] P.009), bleeding (mean [SD] 165.43 ± 368.57 vs 43.25 ± 123.42 P < .001), intestinal injury (20 [4.42%] vs 0 [0.00] P.001), and wound infection (18 [3.98%] vs 2 [0.89%] P.026), while SLC had a higher risk of bile leak (15 [3.31] vs 16 [7.17] P.024). On the multivariable analysis, Charlson comorbidity index (odds ratio [OR], 1.20; CI95%, 1.01-1.42), use of anticoagulant agents (OR, 2.56; CI95%, 1.21-5.44), classification of severity of cholecystitis grade III (OR, 2.96; CI95%, 1.48-5.94), and emergency admission (OR, 6.07; CI95%, 1.33-27.74) were associated with presenting major complications. CONCLUSIONS: SLC was less associated with complications; however, there is scant evidence on its long-term outcomes. Further research is needed on SLC to establish if it is the safest in the long-term as a bailout procedure.

Prevalence and antimicrobial resistance of Escherichia coli and Salmonella spp. in animal feed in Colombia / Prevalencia y resistencia a los antimicrobianos de Escherichia coli y Salmonella spp. en los alimentos para animales en Colombia / Prevalência e resistência a antimicrobianos de Escherichia coli e Salmonella spp. em ração animal na Colômbia

ABSTRACT Objective. To determine the prevalence and antimicrobial resistance of Escherichia coli and Salmonella spp. in animal feed samples collected between 2018 and 2021 in Colombia. Methods. This was a laboratory-based cross-sectional study using routine data from the program for inspection, surveillance, and control of animal feed at the Colombian Agriculture Institute. Samples of animal feed for swine, poultry, canine, feline, leporine, piscine, and equine species were processed for detection of E. coli and Salmonella spp. using enrichment and selective culture methods. Isolates were tested for antimicrobial susceptibility using an automated microdilution method. Results. Of 1 748 animal feed samples analyzed, 83 (4.7%) were positive for E. coli and 66 (3.8%) for Salmonella spp. The presence of E. coli and Salmonella spp. was highest in feed for poultry (6.4% and 5.5%) and swine (6.1% and 4.3%). Antimicrobial resistance testing was performed in 27 (33%) E. coli isolates and 26 (39%) Salmonella isolates. Among E. coli, resistance was most frequently observed to ampicillin (44.5%) followed by cefazolin (33.3%), ciprofloxacin (29.6%), ampicillin/sulbactam (26%), and ceftriaxone (11.1%). The highest resistance levels in Salmonella spp. isolates were against cefazolin (7.7%) and piperacillin/tazobactam (7.7%). Conclusions. This is the first study from Colombia reporting on the prevalence and antimicrobial resistance of E. coli and Salmonella spp. in animal feed samples. Its results establish a baseline over a wide geographical distribution in Colombia. It highlights the need to integrate antimicrobial resistance surveillance in animal feed due to the emergence of resistant bacteria in this important stage of the supply chain.

RESUMEN Objetivo. Determinar la prevalencia y resistencia a los antimicrobianos de Escherichia coli y Salmonella spp. en muestras de piensos para animales tomadas entre el 2018 y el 2021 en Colombia. Métodos. Se trata de un estudio transversal realizado en el laboratorio a partir de los datos regulares del programa de inspección, vigilancia y control de alimentos para animales del Instituto Colombiano Agropecuario. Se procesaron muestras de alimentos utilizados en la cría de cerdos, aves de corral, cánidos, félidos, lepóridos, peces y equinos con el fin de detectar E. coli y Salmonella spp. por medio de métodos de enriquecimiento y cultivo selectivo. Se analizó la sensibilidad a los antimicrobianos de las cepas aisladas mediante microdilución automatizada. Resultados. De 1748 muestras de alimentos analizadas, 83 (4,7%) resultaron positivas para E. coli y 66 (3,8%) para Salmonella spp. La presencia de E. coli y Salmonella spp. fue mayor en los alimentos para aves de corral (6,4% y 5,5%) y cerdos (6,1% y 4,3%). Se realizaron pruebas de resistencia a los antimicrobianos en 27 (33%) cepas de E. coli y 26 (39%) de Salmonella. En las cepas de E. coli, se observó una mayor resistencia a la ampicilina (44,5%), seguida de la resistencia a la cefazolina (33,3%), la ciprofloxacina (29,6%), la ampicilina/sulbactam (26%) y la ceftriaxona (11,1%). En el caso de las cepas de Salmonella spp., los niveles de resistencia más elevados fueron para la cefazolina (7,7%) y piperacilina/tazobactam (7,7%). Conclusiones. Este es el primer estudio realizado en Colombia en el que se informa sobre la prevalencia y la resistencia a los antimicrobianos de E. coli y Salmonella spp. en muestras de alimentos para animales. Sus resultados establecen una línea de base para una zona geográfica mucho mayor dentro de Colombia. Se subraya la necesidad de integrar la vigilancia de la resistencia a los antimicrobianos en los alimentos para animales debido a la aparición de bacterias resistentes en esta importante etapa de la cadena de suministro.

RESUMO Objetivo. Determinar a prevalência e a resistência a antimicrobianos de Escherichia coli e Salmonela spp. em amostras de ração animal coletadas entre 2018 e 2021 na Colômbia. Métodos. Estudo transversal de base laboratorial, usando dados de rotina do programa de inspeção, vigilância e controle de ração animal do Instituto Colombiano de Agricultura. Amostras de ração animal para as espécies suína, avícola, canina, felina, leporina, piscina e equina foram processadas para detecção de E. coli e Salmonella spp., usando métodos de enriquecimento e cultura seletiva. Os isolados foram testados quanto à suscetibilidade a antimicrobianos usando um método automatizado de microdiluição. Resultados. Das 1.748 amostras de ração animal analisadas, 83 (4,7%) foram positivas para E. coli e 66 (3,8%) para Salmonella spp. A presença de E. coli e Salmonella spp. foi maior em rações para aves (6,4% e 5,5%) e suínos (6,1% e 4,3%). O teste de resistência a antimicrobianos foi realizado em 27 (33%) isolados de E. coli e 26 (39%) isolados de Salmonella. Em E. coli, a resistência observada com maior frequência foi à ampicilina (44,5%), seguida da cefazolina (33,3%), ciprofloxacino (29,6%), ampicilina/sulbactam (26%) e ceftriaxona (11,1%). Os maiores níveis de resistência em isolados de Salmonella spp. foram contra cefazolina (7,7%) e piperacilina/tazobactam (7,7%). Conclusões. Este é o primeiro estudo da Colômbia a notificar a prevalência e resistência a antimicrobianos de E. coli e Salmonella spp. em amostras de ração animal. Os resultados estabelecem uma linha de base com ampla distribuição geográfica na Colômbia. Destaca-se a necessidade de integrar a vigilância da resistência a antimicrobianos na ração animal, devido ao surgimento de bactérias resistentes nesta importante etapa da cadeia de abastecimento.

Archivos comunitarios y de derechos humanos como una apuesta por la memoria, la verdad y la resistencia / Community and Human Rights Archives as a Commitment to Memory, Truth, and Resistance

Resumen La reconstrucción de saberes sobre archivos comunitarios de derechos humanos y memoria es de vital importancia para los procesos de transición en países marcados por el conflicto armado como Colombia. Es preciso dar cuenta de procesos pedagógicos realizados por organizaciones de víctimas que diseñaron de manera participativa planes de gestión de archivos comunitarios y que contribuyeron a potenciar las nuevas narrativas de paz y preparar a las organizaciones y comunidades para articular sus experiencias territoriales como una manera de narrar para sus propios territorios, así como para establecer un diálogo con las instancias de justicia y de memoria en Colombia en los escenarios de justicia transicional en ámbitos rurales y urbanos. Se han tomado los casos: Comuna 3 en Medellín y los municipios de Granada e Ituango (Antioquia).

Abstract The reconstruction of knowledge on community archives of human rights and memory is of vital importance for transition processes in countries marked by armed conflict, such as Colombia. It is necessary to account for pedagogical processes carried out by victims' organizations, which designed, in a participatory manner, community archives management plans and that contributed to enhance new peace narratives and to prepare organizations and communities to articulate their territorial experiences as a way of narrating for their own territories, as well as to establish a dialogue with the instances of justice and memory in Colombia in transitional justice scenarios in both rural and urban settings. The cases, which have been taken are Commune 3 in Medellin and the municipalities of Granada and Ituango, Antioquia.

Liquid Biopsy: From Basic Research to Clinical Practice.

Liquid biopsy refers to the molecular analysis in biological fluids of nucleic acids, subcellular structures, especially exosomes, and, in the context of cancer, circulating tumor cells. In the last 10 years, there has been an intensive research in liquid biopsy to achieve a less invasive and more precise personalized medicine. Molecular assessment of these circulating biomarkers can complement or even surrogate tissue biopsy. Because of this research, liquid biopsy has been introduced in clinical practice, especially in oncology, prenatal screening, and transplantation. Here we review the biology, methodological approaches, and clinical applications of the main biomarkers involved in liquid biopsy.

Phase I Trial of DNX-2401 for Diffuse Intrinsic Pontine Glioma Newly Diagnosed in Pediatric Patients.

BACKGROUND: There are no effective treatments for diffuse intrinsic pontine gliomas (DIPGs); these tumors cannot be surgical resected, and diagnosis is based on magnetic resonance imaging. As a result, tumor tissues for molecular studies and pathologic diagnosis are infrequent. New clinical trials are investigating novel medications and therapeutic techniques in an effort to improve treatment of patients with DIPGs. OBJECTIVE: To determine the safety, tolerability, and toxicity of an oncolytic adenovirus, DNX-2401, injected into the cerebellar peduncle in pediatric subjects with DIPG and to collect tumor samples of this type of tumor. METHODS: Phase I, single-center, uncontrolled trial. A tumor biopsy will be performed through the cerebellar peduncle, and DNX-2401 will be injected immediately after the biopsy. Standard therapy consisting of radiotherapy and chemotherapy will follow in 2 to 6 wk. EXPECTED OUTCOMES: Improvement of overall survival and quality of life in patients with DIPG and collection of tumor specimens to study the molecular profiling of these tumors. DISCUSSION: The aims of this trial are to contribute to the sample collection of DIPG and to offer treatment during the tumor tissue biopsy using the virus. If this virus works as expected, it could kill the tumor cells with no damage to healthy tissue, functioning as a targeted therapy. It is important to note that edema has not been observed with this virus in all trials performed to date. The information obtained through this and other similar studies may be useful for developing or improving new therapies in the battle against DIPG.

A cumulative effect involving malfunction of the PTH1R and ATP4A genes explains a familial gastric neuroendocrine tumor with hypothyroidism and arthritis.

BACKGROUND: Type I gastric neuroendocrine tumors (gNETs) classically arise because of hypergastrinemia and involve destruction of parietal cells, which are responsible for gastric acid secretion through the ATP4A proton pump and for intrinsic factor production. METHODS: By whole exome sequencing, we studied a family with three members with gNETs plus hypothyroidism and rheumatoid arthritis to uncover their genetic origin. RESULTS: A heterozygous missense mutation in the ATP4A gene was identified. Carriers of this variant had low ferritin and vitamin B12 levels but did not develop gNETs. A second heterozygous mutation was also uncovered (PTH1R p.E546K). Carriers exhibited hypothyroidism and one of them had rheumatoid arthritis. Gastrin activates parathyroid hormone like hormone/parathyroid hormone 1 receptor (PTH1R) signaling, which is involved in gastric cell homeostasis. Activation of parathyroid hormone/PTH1R, which is upregulated by thyrotropin in the thyroid, is also involved in RANKL expression, which regulates bone homeostasis. Thyrotropin and RANKL expression were deregulated in PTH1R mutation carriers, suggesting a link between the PTH1R gene, hypothyroidism, rheumatoid arthritis, and gastric disease. Only patients with both mutations developed gNETs plus hypothyroidism and rheumatoid arthritis. CONCLUSION: Both mutations suggest that a collaborative mechanism is operative in this family, in which mutations in these genes affect the function and viability of parietal cells and lead to the achlorhydria that drives hypergastrinemia and the formation of gNETs.

The Oncolytic Adenovirus VCN-01 as Therapeutic Approach Against Pediatric Osteosarcoma.

PURPOSE: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Despite aggressive chemotherapy, more than 30% of patients do not respond and develop bone or lung metastasis. Oncolytic adenoviruses engineered to specifically destroy cancer cells are a feasible option for osteosarcoma treatment. VCN-01 is a replication-competent adenovirus specifically engineered to replicate in tumors with a defective RB pathway, presents an enhanced infectivity through a modified fiber and an improved distribution through the expression of a soluble hyaluronidase. The aim of this study is to elucidate whether the use of VCN-01 would be an effective therapeutic strategy for pediatric osteosarcoma. EXPERIMENTAL DESIGN: We used osteosarcoma cell lines established from patients with metastatic disease (531MII, 678R, 588M, and 595M) and a commercial cell line (143B). MTT assays were carried out to evaluate the cytotoxicity of VCN-01. Hexon assays were used to evaluate the replication of the virus. Western blot analysis was performed to assess the expression levels of viral proteins and autophagic markers. The antitumor effect of VCN-01 was evaluated in orthotopic and metastatic osteosarcoma murine animal models. RESULTS: This study found that VCN-01, a new generation genetically modified oncolytic adenovirus, administered locally or systemically, had a potent antisarcoma effect in vitro and in vivo in mouse models of intratibial and lung metastatic osteosarcoma. Moreover, VCN-01 administration showed a safe toxicity profile. CONCLUSIONS: These results uncover VCN-01 as a promising strategy for osteosarcoma, setting the bases to propel a phase I/II trial for kids with this disease. Clin Cancer Res; 22(9); 2217-25. ©2015 AACR.

Biomecánica del hombro y bases fisiológicas de los ejercicios de Codman / Shoulder's biomechanics and physiological basis for the Codman exercise

El hombro se considera la articulación más móvil del cuerpo humano, pero también la más inestable. Ante la presencia de enfermedades en dicha articulación se han empleado técnicas de intervención fisioterapéuticas, entre ellas los ejercicios de Codman, con la finalidad de restablecer la integridad del hombro, sustentándose en sus efectos fisiológicos. El objetivo de esta revisión de tema es describir la biomecánica del hombro como base fundamental de los ejercicios de Codman y sus efectos fisiológicos.

Shoulder is considered the most mobile joint in the human body, but also the most unstable. In the presence of diseases in this joint has been used physiotherapy rehabilitation techniques, including Codman exercises with the aim of restore the integrity of the shoulder, sustained in their physiological effects. The objective of this review is to explain the biomechanics of the shoulder as the foundation of Codman exercises and their physiological effects.

ErbB3 silencing reduces osteosarcoma cell proliferation and tumor growth in vivo.

Osteosarcoma is the most common primary bone tumor in children and adults. Despite improved prognosis, resistance to chemotherapy remains responsible for failure of osteosarcoma treatment. The identification of the molecular signals that contribute to the aberrant osteosarcoma cell growth may provide clues to develop new therapeutic strategies for chemoresistant osteosarcoma. Here we show that the expression of ErbB3 is increased in human osteosarcoma cells in vitro. Tissue microarray analysis of tissue cores from osteosarcoma patients further showed that the ErbB3 protein expression is higher in bone tumors compared to normal bone tissue, and is further increased in patients with recurrent disease or soft tissue metastasis. In murine osteosarcoma cells, silencing ErbB3 using shRNA decreased cell replication, cell migration and invasion, indicating that ErbB3 contributes to tumor cell growth and invasiveness. Furthermore, ErbB3 silencing markedly reduced tumor growth in a murine allograft model in vivo. Immunohistochemal analysis showed that the reduced tumor growth induced by ErbB3 silencing in this model resulted from decreased cell osteosarcoma cell proliferation, supporting a role of ErbB3 in bone tumor growth in vivo. Taken together, the results reveal that ErbB3 expression in human osteosarcoma correlates with tumor grade. Furthermore, silencing ErbB3 in a murine osteosarcoma model results in decreased cell growth and invasiveness in vitro, and reduced tumor growth in vivo, which supports the potential therapeutic interest of targeting ErbB3 in osteosarcoma.

CYR61 downregulation reduces osteosarcoma cell invasion, migration, and metastasis.

Osteosarcoma is the most common primary tumor of bone. The rapid development of metastatic lesions and resistance to chemotherapy remain major mechanisms responsible for the failure of treatments and the poor survival rate for patients. We showed previously that the HMGCoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor statin exhibits antitumoral effects on osteosarcoma cells. Here, using microarray analysis, we identify Cyr61 as a new target of statins. Transcriptome and molecular analyses revealed that statins downregulate Cyr61 expression in human and murine osteosarcoma cells. Cyr61 silencing in osteosarcoma cell lines enhanced cell death and reduced cell migration and cell invasion compared with parental cells, whereas Cyr61 overexpression had opposite effects. Cyr61 expression was evaluated in 231 tissue cores from osteosarcoma patients. Tissue microarray analysis revealed that Cyr61 protein expression was higher in human osteosarcoma than in normal bone tissue and was further increased in metastatic tissues. Finally, tumor behavior and metastasis occurrence were analyzed by intramuscular injection of modified osteosarcoma cells into BALB/c mice. Cyr61 overexpression enhanced lung metastasis development, whereas cyr61 silencing strongly reduced lung metastases in mice. The results reveal that cyr61 expression increases with tumor grade in human osteosarcoma and demonstrate that cyr61 silencing inhibits in vitro osteosarcoma cell invasion and migration as well as in vivo lung metastases in mice. These data provide a novel molecular target for therapeutic intervention in metastatic osteosarcoma.

Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells.

Germline mutations in the Exostoses-1 gene (EXT1) are found in hereditary multiple exostoses syndrome, which is characterized by the formation of osteochondromas and an increased risk of chondrosarcomas and osteosarcomas. However, despite its putative tumor-suppressor function, little is known of the contribution of EXT1 to human sporadic malignancies. Here, we report that EXT1 function is abrogated in human cancer cells by transcriptional silencing associated with CpG island promoter hypermethylation. We also show that, at the biochemical and cellular levels, the epigenetic inactivation of EXT1, a glycosyltransferase, leads to the loss of heparan sulfate (HS) synthesis. Reduced HS production can be reversed by the use of a DNA demethylating agent. Furthermore, the re-introduction of EXT1 into cancer cell lines displaying methylation-dependent silencing of EXT1 induces tumor-suppressor-like features, e.g. reduced colony formation density and tumor growth in nude mouse xenograft models. Screening a large collection of human cancer cell lines (n=79) and primary tumors (n=454) from different cell types, we found that EXT1 CpG island hypermethylation was common in leukemia, especially acute promyelocytic leukemia and acute lymphoblastic leukemia, and non-melanoma skin cancer. These findings highlight the importance of EXT1 epigenetic inactivation, leading to an abrogation of HS biosynthesis, in the processes of tumor onset and progression.

Secondary myelodysplastic syndrome after treatment for promyelocytic leukemia: clinical and genetic features of two cases.

Acute promyelocytic leukemia (APL) represents a biologic and clinically well-defined subtype of acute nonlymphocytic leukemia with specific morphologic and karyotypic characteristics. Although secondary leukemia and myelodysplastic syndromes (MDS) are the most frequent secondary neoplasms following chemotherapy for acute leukemia, their development after complete remission in patients with APL is uncommon. We describe the clinical and genetic features of two APL patients who achieved CR after chemotherapy and all-trans retinoid acid treatment and subsequently developed a MDS. Therapy-related MDS karyotype changes such as abnormalities of chromosomes 5 and 7 were found in the cytogenetic analysis. Since TP53 alteration was detected in one case, possible implications of these findings in the onset of MDS are discussed.