Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

Appropriateness of Immunoglobulin M testing for Measles, Mumps, and Rubella.

INTRODUCTION: Testing for immunity to measles, mumps, and rubella should include only IgG; IgM testing is appropriate only if acute illness is suspected. The appropriateness of measles, mumps, and rubella IgM testing was evaluated in a national administrative dataset. METHODS: Laboratory testing for measles, mumps, and rubella during 2019-2022 was analyzed in 2024 using HealthVerity administrative claims and laboratory data. IgG, IgM, and reverse-transcriptase polymerase chain reaction (RT-PCR) testing are described by year, demographics, and region. IgM testing was examined for appropriateness, defined as an IgM test combined with diagnostic codes indicative of acute illness. RESULTS: During 2019-2022, IgM testing represented a small proportion of serologic testing (measles: 3.3%, mumps: 2.4%, rubella: 2.1%) but appeared to be appropriately performed in only 15.4% of cases for measles, 32.8% of cases for mumps, and 10.2% of cases for rubella. IgM testing was more commonly performed for female patients, with the largest discrepancy seen for rubella (90.5% female vs 9.5% male). IgM for measles and mumps was more often performed appropriately for persons aged 0-19 years (37.6% and 60.1%) compared with persons aged 20-49 years (11.8% and 22.0%) and 50+ years (16.5% and 33.8%). CONCLUSIONS: The majority of IgM testing for measles, mumps, and rubella during this period appeared inappropriate. Clinicians and health systems could ensure that IgG testing alone is performed when evaluating for immunity through modifications to electronic medical records and commercial laboratories could ensure that providers are able to test for IgG alone when evaluating immunity.

Unplanned reoperations: is emergency surgery a risk factor? A cohort study.

BACKGROUND: Unplanned reoperations have been proposed as a quality indicator in surgery but have not been studied extensively, especially concerning risk factors. METHODS: This was a prospective cohort study in a third-level general surgery service. Data regarding patients operated on between July 2007 and February 2008 and followed up for 30 postoperative days were collected. Unplanned reoperations were the primary end point. The secondary end points were 30-d mortality and length of stay. A multivariate logistic regression analysis evaluated the hypothesis that patients operated on in emergency conditions had a greater chance of being reoperated on, after adjusting for relevant covariates. RESULTS: There was a 5.9% cumulative incidence of unplanned reoperations. Patients operated on in emergency conditions had a 1.79 crude relative risk (RR) (95% confidence interval [CI], 1.15-2.78) of reoperation. Reoperated patients' RR of mortality was 8.94 (95% CI, 6.11-13.07). The mean postoperative hospital stay was 3d for patients who were not reoperated on and 19d for those who were reoperated on (P=0.00001). The logistic regression model gave a 2.83 odds ratio (95% CI, 1.65-4.87) for reoperation on emergency patients when adjusted for age, gender, body mass index, American Society of Anesthesiology classification, intraoperative inotropic use, and operation complexity. CONCLUSIONS: Tertiary general surgery service patients had a significantly increased risk of being reoperated on if the initial surgery was an emergency surgery compared with elective surgery. Unplanned reoperations led to a significantly increased mortality risk and a longer postoperative hospital stay, which could be regarded as warning signs in the care of surgical patients.

HOSPITAL VOLUME, POSTOPERATIVE MORTALITY, AND COSTS AFTER GASTRECTOMY FOR GASTRIC CANCER IN COLOMBIA: IS THERE ANY ASSOCIATION?

BACKGROUND: There are no information in the literature associating the volume of gastrectomies with survival and costs for the health system in the treatment of patients with gastric cancer in Colombia. AIMS: The aim of this study was to analyze how gastrectomy for gastric cancer is associated with hospital volume, 30-day and 180-day postoperative mortality, and healthcare costs in Bogotá, Colombia. METHODS: A retrospective cohort study based on hospital data of all adult patients with gastric cancer who underwent gastrectomy between 2014 and 2016 using a paired propensity score. The surgical volume was identified as the average annual number of gastrectomies performed by the hospital. RESULTS: A total of 743 patients were included in the study. Hospital mortality at 30 and 180 days postoperatively was 36 (4.85%) and 127 (17.09%) patients, respectively. The average health care cost was USD 3,200. A total of 26 or more surgeries were determined to be the high surgical volume cutoff. Patients operated on in hospitals with a high surgical volume had lower 6-month mortality (HR 0.44; 95%CI 0.27-0.71; p=0.001), and no differences were found in health costs (mean difference 398.38; 95%CI-418.93-1,215.69; p=0.339). CONCLUSIONS: This study concluded that in Bogotá (Colombia), surgery in a high-volume hospital is associated with better 6-month survival and no additional costs to the health system.

Fragmentation of Care and Its Association With Survival and Costs for Patients With Breast Cancer in Colombia.

PURPOSE: Breast cancer care requires a multimodal approach and a multidisciplinary team who must work together to obtain good clinical results. The fragmentation of care can affect the breast cancer care; however, it has not been measured in a low-resource setting. The aim of this study was to identify fragmentation of care, the geographic variation of this and its association with 4-year overall survival (OS), and costs of care for patients with breast cancer enrolled in Colombia's contributory health care system. MATERIALS AND METHODS: A retrospective cohort study was conducted using administrative databases. Women with breast cancer who were treated from January 1, 2013, to December 31, 2015, were included. Fragmentation of care was the exposure, which was measured by the number of different health care provider institutions (HCPIs) that treated a patient during the first year after diagnosis. Crude mortality rates were estimated, survival functions were calculated using the nonparametric Kaplan-Meier approach, and adjusted hazard ratios (HRs) were estimated using multivariate Cox regression model to identify the association of fragmentation with 4-year OS. The association between fragmentation and costs of care was assessed using a multivariate linear regression model. RESULTS: A total of 10,999 patients with breast cancer were identified, and 1,332 deaths were observed. The 4-year crude mortality rate was 31.97 (95% CI, 30.25 to 33.69) per 1,000 person-years for the whole cohort, and the highest rate was in the cohort defined for the fourth quartile of the fragmentation measurement (eight or more HCPIs), 40.94 (95% CI, 36.49 to 45.39). The adjusted HR for 4-year OS was 1.04 (95% CI, 1.01 to 1.07) for each HCPI additional. The cost of care is increased for each additional HCPIs (cost ratio, 1.25; 95% CI, 1.23 to 1.26). CONCLUSION: Fragmentation of care decreases overall 4-year OS and increases the costs of care in women with breast cancer for Colombia.

Translation, adaptation, and validation of the MeNTS score in colombian population: The MeNTS Col score.

Objective: To evaluate and validate the medically necessary and time sensitive score by testing the variables, in order to create a surgical preoperative score for procedure prioritization in COVID-19 pandemic in Colombia. Methods: A multicenter retrospective cross-sectional study of instrument validation with a cultural adaptation and translation into the Spanish language was carried out in Bogota, Colombia. Patients over 18 years of age who had undergone elective procedures of general surgery and subspecialties were included. The translation of the medically necessary and time sensitive score into Spanish was performed independently by two bilingual surgeons fluent in both English and Spanish. A final version of the Spanish questionnaire (MeNTS Col) for testing was then produced by an expert committee. After translation and cultural adaptation, it was submitted to evaluate the psychometric properties of the medically necessary and time sensitive score. Cronbach's α was used to represent and evaluate the internal consistency and assess reliability. Results: A total of 172 patients were included, with a median age of 54 years; of which 96 (55.8%) patients were females. The vast majority of patients were treated for general surgery (n = 60) and colon and rectal surgery (n = 31). The evaluation of the internal consistency of the scale items in Spanish version was measured, and values of 0.5 for 0.8 were obtained. In the reliability and validation process, Cronbach's α values in all items remained higher than 0.7. The new MeNTS Col model was analyzed, and a result of 0.91 was obtained. Conclusions: The Spanish version of the medically necessary and time sensitive, the MeNTS Col score, and its respective Spanish translation perform similarly to the original version. Therefore, they can be useful and reproducible in Latin American countries.

Communicating climate change and biodiversity loss with local populations: exploring communicative utopias in eight transdisciplinary case studies.

Climate change and biodiversity loss trigger policies targeting and impacting local communities worldwide. However, research and policy implementation often fail to sufficiently consider community responses and to involve them. We present the results of a collective self-assessment exercise for eight case studies of communications with regard to climate change or biodiversity loss between project teams and local communities. We develop eight indicators of good stakeholder communication, reflecting the scope of Verran's (2002) concept of postcolonial moments as a communicative utopia. We demonstrate that applying our indicators can enhance communication and enable community responses. However, we discover a divergence between timing, complexity and (introspective) effort. Three cases qualify for postcolonial moments, but scrutinising power relations and genuine knowledge co-production remain rare. While we verify the potency of various instruments for deconstructing science, their sophistication cannot substitute trust building and epistemic/transdisciplinary awareness. Lastly, we consider that reforming inadequate funding policies helps improving the work in and with local communities.

Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial.

BACKGROUND: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. METHODS: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. FINDINGS: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). INTERPRETATION: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. FUNDING: Agency for Healthcare Research and Quality and the National Cancer Institute. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Mammea B/BA Isolated From the Seeds of Mammea americana L. (Calophyllaceae) is a Potent Inhibitor of Methicillin-Resistant Staphylococcus aureus.

Staphylococcus aureus remains a pathogen of high concern in public health programs worldwide due to antibiotic resistance and emergence of highly virulent strains. Many phytochemicals have demonstrated activity against S. aureus and other Gram-positive bacteria, but the minimum inhibitory concentration (MIC) values comparable to commonly used antibiotics are needed. In the present study, bio-guided fractionation of the ethanol extract of seeds of Mammea americana L. (Calophyllaceae) throughout the antibacterial activity, against S. aureus strains that are sensitive and resistant to methicillin, led to the isolation of four coumarins identified as mammea B/BA, mammea B/BC, mammea A/AA cyclo D and mammea A/AA cyclo F, and a mixture of mammea B/BA cyclo F plus mammea B/BD cyclo F. The extract inhibited the growth of S. aureus with MIC values of 2-4 µg/ml and Mammea B/BA (MaBBA) presented MIC values in a range between 0.5 and 1.0 µg/ml in six methicillin-sensitive strains and eight methicillin-resistant strains evaluated. We consider MaBBA the most potent of all mammea coumarins reported to date, according to the literature review carried out at the time of writing of this article. Toxicity assessment in vivo against the nematode Caenorhabditis elegans and in vitro against human fibroblasts of the extract and the compound MaBBA indicated that both had low toxicity.

Optimization of municipal solid waste collection routes in a Latin-American context.

Latin-American cities need efficient municipal solid waste (MSW) collection systems, specifically in municipalities with fast urbanization. Poor logistics in collection routes is one of the causes of inefficient MSW management. A strategy for designing the MSW collection routes, considering an environmental and economic analysis, was developed and tested in the Metropolitan Area of Monterrey (MMA), one of the cities with the highest urban and economic development in Mexico. Life cycle assessment and costs analysis were performed to evaluate archetypal routes' environmental and economic impact in the current MSW collection system. The assessment of the environmental impact was realized through midpoint indicators of the ReCiPe 2008 method. The mathematical model describing the collection routes was developed using actual data from the MSW collection system in MMA, optimized by the Traveling Salesman Problem (TSP), and solved in RStudio. This study shows a reduction of between 9 and 20% of greenhouse gas emissions and distance covered in current collection stages, respectively. The results also demonstrate the influence of road direction, collection-truck efficiency, and traffic load in different stage on the environmental and economic impacts of the collection routes. A life cycle inventory, with realistic inputs and outputs of the MSW collection system, was developed. These inventories are scarce in Mexico and Latin America; their development helps designing cleaner MSW collection systems.Implications: The optimization of urban solid waste collection systems is a strategy to reduce costs and environmental impacts, considering factors such as distance or fuel consumption. However, mathematical models within the optimization require detailed information of the road network to achieve reliable results. In this context, Latin America shows difficulties in increasing its collection systems' efficiency due to economic constraints and limited access to information from locals governments. The use of geographic information systems has been shown to collect real data on a city's roads. This work aims to propose a strategy for designing urban solid waste collection routes with the least environmental and economic impacts through an optimization strategy that considers the road network's real-time data, added to an environmental analysis developed with a life cycle assessment approach. We believe that our results could help the design of urban solid waste collection systems for cities with Latin American characteristics. Additionally, an inventory of specific inputs and emissions for waste collection in this type of city will be generated, supporting future sustainable management strategies.

Regulation of vimentin intermediate filaments in endothelial cells by hypoxia.

Hypoxia triggers responses in endothelial cells that play roles in many conditions including high-altitude pulmonary edema and tumor angiogenesis. Signaling pathways activated by hypoxia modify cytoskeletal and contractile proteins and alter the biomechanical properties of endothelial cells. Intermediate filaments are major components of the cytoskeleton whose contribution to endothelial physiology is not well understood. We have previously shown that hypoxia-activated signaling in endothelial cells alters their contractility and adhesiveness. We have also linked p38-MAP kinase signaling pathway leading to HSP27 phosphorylation and increased actin stress fiber formation to endothelial barrier augmentation. We now show that vimentin, a major intermediate filament protein in endothelial cells, is regulated by hypoxia. Our results indicate that exposure of endothelial cells to hypoxia causes vimentin filament networks to initially redistribute perinuclearly. However, by 1 hour hypoxia these networks reform and appear more continuous across cells than under normoxia. Hypoxia also causes transient changes in vimentin phosphorylation, and activation of PAK1, a kinase that regulates vimentin filament assembly. In addition, exposure to 1 hour hypoxia increases the ratio of insoluble/soluble vimentin. Overexpression of phosphomimicking mutant HSP27 (pmHSP27) causes changes in vimentin distribution that are similar to those observed in hypoxic cells. Knocking-down HSP27 destroys the vimentin filamentous network, and disrupting vimentin filaments with acrylamide increases endothelial permeability. Both hypoxia- and pmHSP27 overexpression-induced changes are reversed by inhibition of phosphatase activity. In conclusion hypoxia causes redistribution of vimentin to a more insoluble and extensive filamentous network that could play a role in endothelial barrier stabilization. Vimentin redistribution appears to be mediated through altering the phosphorylation of the protein and its interaction with HSP27.

Modulation of HSP27 alters hypoxia-induced endothelial permeability and related signaling pathways.

This manuscript describes how the permeability of pulmonary artery microvascular endothelial cell (RPMEC) monolayer is elevated by hypoxia and the role played by HSP27 phosphorylation. p38 MAP kinase activation leading to HSP27 phosphorylation was previously shown by our laboratory to alter the actin cytoskeleton and tethering properties of RPMEC. This effect was independent of hypoxia-induced contractility which was ROCK-dependent rather than HSP27-dependent. Results described here show that increased HSP27 phosphorylation not only does not underlie hypoxia-induced permeability, but may actually augment the endothelial barrier. Hypoxia causes gap formation between RPMEC and increases MLC2 phosphorylation. The phosphorylation of MYPT1, which inhibits MLC2 phosphatase, is also increased in hypoxia. In addition, FAK phosphorylation, which alters focal adhesion signaling, is increased in hypoxia. Overexpressing phosphomimicking HSP27 (pmHSP27), which induces significant actin stress fiber formation, surprisingly renders RPMEC resistant to hypoxia- or TGFbeta-induced permeability. siRNA against pmHSP27 reverses the increased actin stress fiber formation in pmHSP27-overexpressing cells, and disrupting actin stress fibers in pmHSP27-overexpressing RPMEC renders them more susceptible to hypoxia. Finally, hypoxia-induced gap formation, as well as phosphorylation of MLC2, MYPT1 and FAK are almost abolished by overexpressing pmHSP27 in RPMEC. These effects of pmHSP27 overexpression might represent decreased cytoskeletal plasticity and increased tethering which counteracts permeability-inducing contractility. Thus hypoxia activates two pathways one leading to contractility and increased permeability, the other leading to actin stress fibers, stronger adhesion, and reduced permeability. Altering HSP27 phosphorylation, which tips the balance towards decreased permeability, might be targeted in managing endothelial barrier dysfunction.

Towards future-oriented conservation: Managing protected areas in an era of climate change.

Management of protected areas must adapt to climate impacts, and prepare for ongoing ecological transformation. Future-Proofing Conservation is a dialogue-based, multi-stakeholder learning process that supports conservation managers to consider the implications of climate change for governance and management. It takes participants through a series of conceptual transitions to identify new management options that are robust to a range of possible biophysical futures, and steps that they can take now to prepare for ecological transformation. We outline the Future-Proofing Conservation process, and demonstrate its application in a pilot programme in Colombia. This process can be applied and adapted to a wide range of climate adaptation contexts, to support practitioners in developing positive ways forward for management and decision-making. By acknowledging scientific uncertainty, considering social values, and rethinking the rules that shape conservation governance, participants can identify new strategies towards "future-oriented conservation" over the long term.

Hospital volume, postoperative mortality, and costs after gastrectomy for gastric cancer in colombia: is there any association? / Volume hospitalar, mortalidade pós-operatória e custos após gastrectomia por câncer gástrico na colômbia: existe associação?

ABSTRACT BACKGROUND: There are no information in the literature associating the volume of gastrectomies with survival and costs for the health system in the treatment of patients with gastric cancer in Colombia. AIMS: The aim of this study was to analyze how gastrectomy for gastric cancer is associated with hospital volume, 30-day and 180-day postoperative mortality, and healthcare costs in Bogotá, Colombia. METHODS: A retrospective cohort study based on hospital data of all adult patients with gastric cancer who underwent gastrectomy between 2014 and 2016 using a paired propensity score. The surgical volume was identified as the average annual number of gastrectomies performed by the hospital. RESULTS: A total of 743 patients were included in the study. Hospital mortality at 30 and 180 days postoperatively was 36 (4.85%) and 127 (17.09%) patients, respectively. The average health care cost was USD 3,200. A total of 26 or more surgeries were determined to be the high surgical volume cutoff. Patients operated on in hospitals with a high surgical volume had lower 6-month mortality (HR 0.44; 95%CI 0.27-0.71; p=0.001), and no differences were found in health costs (mean difference 398.38; 95%CI-418.93-1,215.69; p=0.339). CONCLUSIONS: This study concluded that in Bogotá (Colombia), surgery in a high-volume hospital is associated with better 6-month survival and no additional costs to the health system.

RESUMO RACIONAL: Não há informações na literatura relacionando o volume de gastrectomias bem como a sobrevida e os custos para o sistema de saúde, no tratamento de pacientes com câncer gástrico na Colômbia. OBJETIVOS: analisar como a gastrectomia para câncer gástrico está associada ao volume hospitalar, mortalidade pós-operatória de 30 e 180 dias e custos de saúde em Bogotá, Colômbia. MÉTODOS: Estudo de coorte retrospectivo baseado em dados hospitalares de todos os pacientes adultos com câncer gástrico submetidos à gastrectomia entre 2014 e 2016, utilizando um escore de propensão pareado. O volume cirúrgico foi identificado como o número médio anual de gastrectomias realizadas pelo hospital. RESULTADOS: Foram incluídos no estudo 743 pacientes. A mortalidade hospitalar aos 30 e 180 dias de pós-operatório, foram respectivamente, 36 (4,85%) e 127 (17,09%) pacientes. O custo médio de saúde foi de US$ 3.200. Vinte e seis ou mais cirurgias foram determinadas como ponto de corte de alto volume cirúrgico. Pacientes operados em hospitais de alto volume cirúrgico tiveram menor mortalidade em seis meses (HR 0,44; IC95% 0,27-0,71; p=0,001) e não foram encontradas diferenças nos custos com saúde (diferença média 398,38; IC95% −418,93-1215,69; p=0,339). CONCLUSÕES: Este estudo concluiu que em Bogotá (Colômbia), a cirurgia em um hospital com alto volume cirúrgico está associada a uma melhor sobrevida de seis meses e não há custos adicionais para o sistema de saúde.

Lack of MK2 inhibits myofibroblast formation and exacerbates pulmonary fibrosis.

Fibroblasts play a major role in tissue repair and remodeling. Their differentiation into myofibroblasts, marked by increased expression of smooth muscle-specific alpha-actin (alpha-SMA), is believed to be important in wound healing and fibrosis. We have recently described a role for MK2 in this phenotypic differentiation in culture. In this article, we demonstrate that MK2 also regulates myofibroblasts in vivo. Disruption of MK2 in mice prevented myofibroblast formation in a model of pulmonary fibrosis. However, MK2 disruption and consequent lack of myofibroblast formation exacerbated fibrosis rather than ameliorated it as previously postulated. When mice lacking MK2 (MK2-/-) were exposed to bleomycin, more collagen accumulated and more fibroblasts populated fibrotic regions in their lungs than in similarly treated wild-type mice. While there were many vimentin-positive cells in the bleomycin-treated MK2-/- mouse lungs, few alpha-SMA-positive cells were observed in these lungs compared with wild-type mouse lungs. siRNA against MK2 reduced alpha-SMA expression in wild-type mouse embryonic fibroblasts (MEF), consistent with its suppression in MK2-/- MEF. On the other hand expressing constitutively active MK2 in MK2-/- MEF significantly increased alpha-SMA expression. MK2-/-MEF proliferated at a faster rate and produced more collagen; however, they migrated at a slower rate than wild-type MEF. Overexpressing phosphomimicking HSP27, a target of MK2, did not reverse the effect of MK2 disruption on fibroblast migration. MK2 disruption did not affect Smad2 activation by transforming growth factor-beta. Thus, MK2 appears to mediate myofibroblast differentiation, and inhibiting that differentiation might contribute to fibrosis rather than protect against it.

Cirugía radioguíada con análogos de somatostatina radiomarcados en tumores neuroendocrinos: reporte de caso / Radioguided surgery with radiolabeled somatostatin analogues in neuroendocrine tumors: Case report

Resumen Introducción: El mejor tratamiento para los tumores neuroendocrinos es la resección completa del tumor, los ganglios, e inclusive en casos seleccionados, las metástasis a distancia. En ocasiones, el tumor primario es pequeño y de difícil localización preoperatoria o sus recaídas pueden ser difíciles de localizar en el terreno de fibrosis por cirugías o tratamientos previos. La cirugía radioguíada ofrece una opción adicional de localización intraoperatoria que hasta ahora no ha sido muy utilizada en tumores neuroendocrinos. Presentación del caso: Paciente de 59 años con antecedente de resección atípica de duodeno y páncreas por tumor neuroendocrino grado 2 del duodeno un año antes. En la tomografía por emisión de positrones/tomografía computarizada (PET/CT) 68Ga-DOTANOC se encontró un ganglio con sobreexpresión de receptores de somatostatina en el mesenterio, sin otras lesiones a distancia. Por los antecedentes quirúrgicos y la dificultad de visualizar la lesión en las imágenes anatómicas (resonancia magnética [RM]) se decidió realizar la cirugía radioguíada. En el preoperatorio se administraron 15 mCi de tecnecio 99 metaestable-hidrazinonicotinilo-Tyr3-octreotida (99mTc-HYNIC-TOC) y se verificó la buena captación en el ganglio. En cirugía, luego de la disección inicial se utilizó la sonda gamma, que detectó una actividad 5 veces mayor en el ganglio, comparado con los tejidos vecinos, lo que permitió su localización y resección. La evolución fue adecuada y un año después no hay evidencia de recaídas. Conclusión: La cirugía radioguíada no ha sido muy utilizada en la localización intraoperatoria de tumores neuroendocrinos, pero es una buena alternativa en casos seleccionados, como el presentado en este artículo, y permite la detección intraoperatoria y su resección completa.

Abstract Introduction: The best treatment for neuroendocrine tumors is complete resection of the tumor, lymph nodes, and even distant metastases in selected cases. Sometimes, the primary tumor is small and difficult to detect before surgery, or its relapses may be difficult to locate in the fibrosis field due to previous surgeries or treatments. Although radioguided surgery allows for additional intraoperative localization, it has yet to be widely used in neuroendocrine tumors. Case report: A 59-year-old patient with a history of atypical resection of duodenum and pancreas due to grade 2 neuroendocrine tumor of the duodenum one year earlier. On 68Ga-DOTANOC PET/CT, a node with somatostatin receptor overexpression was found in the mesentery, with no other distant lesions. Due to the surgical history and the difficulty in visualizing the lesion on anatomical images (MRI), it was decided to perform the radioguided surgery. During the preoperative period, 15 mCi of 99mTc-HYNIC-TOC were administered verifying good uptake in the ganglion. Following the initial dissection, a gamma probe was used, detecting 5 times more activity in the ganglion than in adjacent tissues, allowing for localization and resection. The patient's progress was satisfactory, and one year later there is no evidence of relapse. Conclusion: Although radioguided surgery is not commonly used in the intraoperative location of neuroendocrine tumors, it is a viable option in some situations, such as the one presented here, because it allows for intraoperative detection and full resection.

Síndrome de Kounis, a propósito de un caso / Kounis syndrome, apropos of a case

El síndrome de Kounis se caracteriza por un compromiso cardiaco que es secundario a una respuesta alérgica. Hay pocos datos acerca de la epidemiologia de esta enfermedad debido a su reciente descripción. Se presenta el caso de una paciente mujer de 46 años sin antecedentes de importancia que presentó dolor tipo cólico episódico en hipocondrio derecho de 4 días de tiempo de enfermedad, en la que se consideró el diagnóstico de cólico de origen biliar. Quince minutos luego de manejo sintomático (hiocsina/dipirona), la paciente presentó dolor torácico en región precordial de inicio súbito. La evaluación física mostró hipotensión, taquicardia, presencia de habones en todo el cuerpo y sibilantes a la auscultación pulmonar. El electrocardiograma mostro infradesnivel del segmento ST. Considerado como síndrome coronario agudo, se realizó el manejo con esteroides y soporte vital, y se indicó monitorización cardiovascular en unidad de cuidados intensivos. La paciente egresó sin complicación luego de unos días

Kounis syndrome is defined as an acute coronary syndrome secondary to an allergic response; and it is also known as allergic angina - acute myocardial infarction. There is little data on the epidemiology of this disease because of having been recently described. We present the case of a 46-year old woman who developed an episode of colicky abdominal pain in the right upper quadrant for 4 days, and a diagnosis of abdominal pain of biliary origin was considered. Fifteen minutes after symptomatic therapy was administered (hyoscine and metamizole), the patient developed sudden chest pain. Physical examination revealed hypotension, tachycardia, rash, and wheezing. The electrocardiogram showed ST segment depression. The case was managed as an acute coronary syndrome, vital support and steroids were part of its management, and the patient was admitted in the intensive care unit for coronary monitoring. A few days later, the patient was uneventfully discharged