Phase I clinical trial of the feasibility and safety of direct peritoneal resuscitation in liver transplantation.

BACKGROUND: Direct peritoneal resuscitation (DPR) is associated with improved outcomes in trauma. Animal models suggest DPR has favorable effects on the liver. We sought to evaluate its safety and assess for improved outcomes in liver transplantation (LT). METHODS: LT patients with renal dysfunction and/or obesity were enrolled in a phase-I clinical trial. DPR lasted 8-24 â€‹h depending on postoperative disposition. Primary outcome was percent of patients completing DPR. Secondary outcomes evaluated complications. Controls with either obesity (control-1) or both risk factors (obesity â€‹+ â€‹renal dysfunction, control-2) were analyzed. RESULTS: Fifteen patients were enrolled (seven with both criteria and eight with obesity alone). DPR was completed in 87 â€‹% of patients, with one meeting stopping criteria. Controls included 45 (control-1) and 24 (control-2) patients. Return to operating room, graft loss, and late infections were lower with DPR. CONCLUSION: DPR appears to be safe in closed abdomens following LT, warranting a follow-up phase-II trial to assess efficacy.

Fibrinolysis Resistance After Injury Is a Risk Factor for a Hospital-Acquired Pneumonia-Like Disease Pattern.

Background: Pneumonia is associated with increased morbidity and costs in the intensive care unit (ICU). Its early identification is key for optimal outcomes, but early biomarkers are lacking. Studies suggest that fibrinolysis resistance (FR) after major abdominal surgery is linked to an increased risk of infection. Patients and Methods: Patients in a randomized controlled trial for hemorrhagic shock were evaluated for FR. Fibrinolysis resistance was quantified by thrombelastography with exogenous tissue plasminogen activator (tPA-TEG) at 24- and 48-hours post-injury and measuring LY30 (%). A receiver-operating characteristics (ROC) curve analysis was used to identify a cutoff for increased risk of pneumonia, which was then validated in ICU patients at risk for venous thromboembolism (VTE). Multivariable logistic regression was used to control for confounders. Results: Forty-nine patients in the hemorrhagic shock cohort had tPA-TEGs at 24- and 48-hours (median ISS, 27; 7% pneumonia). A composite tPA-TEG LY30 of less than 4% at 24 and 48 hours was found to be the optimal cutoff for increased risk of pneumonia. This cohort had a seven-fold increased rate of pneumonia (4% vs. 28%; p = 0.048). Eighty-eight patients in the VTE cohort had tPA-TEGs at 24 and 48 hours post-ICU admission (median ISS, 28; 6% pneumonia). The tPA-TEG LY30 of less than 4% was associated with a 10-fold increased rate of pneumonia (19% vs. 1.5%; p = 0.002). In patients with traumatic brain injury, the same association was found (33% vs. 3.2%; p = 0.006). Adjusting for confounders, the tPA-TEG persisted as a substantial risk factor for pneumonia (adjusted odds ratio [OR], 35.7; 95% confidence interval [CI], 1.9-682; p = 0.018). Conclusions: Fibrinolysis resistance quantified by tPA-TEG within 48 hours of ICU admission is associated with an increased risk of pneumonia in patients in hemorrhagic shock and those at risk for VTE. Prospective validation of the tPA-TEG LY30 optimal cutoff for pneumonia and further investigation into whether endogenous FR is a cause of an altered immunity is warranted.

Usefulness of 18F-FDG PET-CT for assessing large-vessel involvement in patients with suspected giant cell arteritis and negative temporal artery biopsy.

OBJECTIVE: To investigate the usefulness of 18F-FDG PET-CT for assessing large-vessel (LV) involvement in patients with suspected giant cell arteritis (GCA) and a negative temporal artery biopsy (TAB). METHODS: A retrospective review of our hospital databases was conducted to identify patients with suspected GCA and negative TAB who underwent an 18F-FDG PET-CT in an attempt to confirm the diagnosis. The gold standard for GCA diagnosis was clinical confirmation after a follow-up period of at least 12 months. RESULTS: Out of the 127 patients included in the study, 73 were diagnosed with GCA after a detailed review of their medical records. Of the 73 patients finally diagnosed with GCA, 18F-FDG PET-CT was considered positive in 61 cases (83.5%). Among the 54 patients without GCA, 18F-FDG PET-CT was considered positive in only eight cases (14.8%), which included 1 case of Erdheim-Chester disease, 3 cases of IgG4-related disease, 1 case of sarcoidosis, and 3 cases of isolated aortitis. Overall, the diagnostic performance of 18F-FDG PET-CT for assessing LV involvement in patients finally diagnosed with GCA and negative TAB yielded a sensitivity of 83.5%, specificity of 85.1%, and a diagnostic accuracy of 84% with an area under the ROC curve of 0.844 (95% CI: 0.752 to 0.936). The sensitivity was 89% in occult systemic GCA and 100% in extracranial LV-GCA. CONCLUSION: Our study confirms the utility of 18F-FDG PET-CT in patients presenting with suspected GCA and a negative TAB by demonstrating the presence of LV involvement across different subsets of the disease.

Esquema para mejorar el aprendizaje sobre el Análisis de la Situación de Salud / Scheme to improve learning about Health Situation Analysis / Scheme to improve learning about Health Situation Analysis / Esquema para melhorar o aprendizado sobre Análise da Situação de Saúde

Introducción: El análisis de la situación de salud es una investigación primordial que se realiza en el sistema de salud cubano, en el que se estudia la salud, los elementos que la determinan y las formas de mejorarla. Objetivo: Evaluar la propuesta de diseño de un esquema que contribuya a la mejora del aprendizaje del análisis de la situación de salud de la comunidad para los residentes de la especialidad Medicina General Integral, pertenecientes a la Universidad de Ciencias Médicas de Guantánamo. Método: Se realizó una investigación pedagógica de tipo descriptiva en la antes mencionada institución durante el período marzo-julio de 2022. De un universo de 67 profesores que aceptaron participar, se seleccionaron 26 por muestreo intencional. Para obtener los datos primarios fueron aplicados tres cuestionarios tipo Likert para evaluar el esquema, en consideración con la estructura, la funcionalidad y el aporte en el aprendizaje. Dichos cuestionarios incluyeron las respuestas: Totalmente en desacuerdo, En desacuerdo, Ni de acuerdo ni en desacuerdo, De acuerdo y Totalmente de acuerdo. Los datos se resumieron en números absolutos y porcentajes. Se presentaron en tablas de distribución de frecuencias. Resultados: Los subtotales de respuestas Totalmente de acuerdo y De acuerdo sobre la evaluación estructural y funcional, así como la influencia que se espera de este para mejorar el aprendizaje del análisis de situación de salud, se consideraron adecuados al superar el estándar. Conclusiones: El esquema propuesto es evaluado como adecuado en estructura y funcionalidad. Se considera positiva la influencia que se espera de este para mejorar el aprendizaje del análisis de situación de salud de la comunidad.(AU)

Introduction: The analysis of the health situation is a fundamental investigation carried out in the Cuban health system, in which health is studied, the elements that determine it and the ways to improve it. Objective: To evaluate the design proposal of a scheme that contributes to the improvement of learning of the analysis of the health situation of the community for the residents of the Comprehensive General Medicine specialty, belonging to the Universidad de Ciencias Médicas de Guantánamo. Method: A descriptive pedagogical research was carried out in the aforementioned institution during the period March-July 2022. From a universe of 67 teachers who agreed to participate, 26 were selected by intentional sampling. To obtain primary data, three Likert-type questionnaires were applied to evaluate the scheme, taking into consideration the structure, functionality and contribution to learning. These questionnaires included the responses: Totally disagree, Disagree, Neither agree nor disagree, Agree and Totally agree. Data were summarized in absolute numbers and percentages. They were presented in frequency distribution tables. Results: The subtotals of Completely Agree and Agree responses on the structural and functional evaluation, as well as the expected influence of this to improve the learning of health situation analysis, were considered adequate when exceeding the standard. Conclusions: The proposed scheme is evaluated as adequate in structure and functionality. The influence expected from this to improve learning about the analysis of the community's health situation is considered positive.(AU)

Introdução: A análise da situação sanitária é uma investigação fundamental realizada no sistema de saúde cubano, no qual se estuda a saúde, os elementos que a determinam e as formas de melhorá-la. Objetivo: Avaliar a proposta de desenho de um esquema que contribua para a melhoria da aprendizagem da análise da situação de saúde da comunidade para os residentes da especialidade Medicina Geral Integral, pertencente à Universidad de Ciencias Médicas de Guantánamo. Método: Foi realizada uma pesquisa pedagógica descritiva na referida instituição durante o período de março a julho de 2022. De um universo de 67 professores que aceitaram participar, 26 foram selecionados por amostragem intencional. Para obtenção dos dados primários, foram aplicados três questionários do tipo Likert para avaliação do esquema, levando em consideração a estrutura, funcionalidade e contribuição para a aprendizagem. Esses questionários incluíram as respostas: Discordo totalmente, Discordo, Nem concordo nem discordo, Concordo e Concordo totalmente. Os dados foram resumidos em números absolutos e porcentagens. Eles foram apresentados em tabelas de distribuição de frequência. Resultados: Os subtotais das respostas Concordo Totalmente e Concordo na avaliação estrutural e funcional, bem como a influência esperada desta para melhorar a aprendizagem da análise da situação de saúde, foram considerados adequados quando excedem o padrão. Conclusões: O esquema proposto é avaliado como adequado em estrutura e funcionalidade.A influência que se espera disto para melhorar a aprendizagem sobre a análise da situação de saúde da comunidade é considerada positiva.(AU)

Effects of an antioxidants cocktail on glucose metabolism at rest, during exercise, and during a glucose load in healthy young subjects

Background: Reactive oxygen species (ROS) regulate glucose metabolism (GM) in skeletal muscle by improving the translocation of GLUT4. Antioxidant supplementation could block this physiological effect, altering glucose signaling during exercise. However, there is limited evidence in humans on whether antioxidant intake affects GM. Therefore, we aimed to determine the effect of an antioxidant cocktail (AOC) on GM at rest and during metabolic challenges. Methods: Ten healthy male subjects received AOC supplementation (1000 mg of Vitamin C, 600 IU of Vitamin E, and 600 mg of α-lipoic acid) or placebo (2.000 mg of talc) before two trials conducted 7 days apart. Trial 1: AOC 120 and 90 minutes before an endurance exercise (EEX) bout at 60 % of maximal oxygen uptake (VO2max); Trial 2: AOC 120 and 90 minutes before an oral glucose tolerance test (OGTT; 75 g glucose). Measurements of gas exchange and capillary blood samples were collected every 15 minutes during both trials. Results: AOC supplementation increased resting glucose levels (p<0.05). During Trial 1 (EEX), the AOC increased carbohydrate oxidation (CHOox) (p= 0.03), without effect in glucose blood levels. During Trial 2 (OGTT), the AOC supplementation had no significant effect on GM parameters. Conclusion: Acute supplementation with AOC increased resting glucose levels and CHOox during EEX in healthy subjects, with no effect on GM during the OGTT.

Antecedentes: Las especies reactivas de oxígeno (ROS) regulan el metabolismo de la glucosa (GM) en el músculo esquelético al mejorar la translocación de GLUT4. La suplementación con antioxidantes podría bloquear este efecto fisiológico, alterando la señalización de la glucosa durante el ejercicio. Sin embargo, existe evidencia limitada en humanos sobre si la ingesta de antioxidantes afecta el GM. Por lo tanto, nuestro objetivo fue determinar el efecto de un cóctel de antioxidantes (AOC) en el GM en reposo y durante desafíos metabólicos. Métodos: Sujetos sanos (sexo masculino; n= 10) recibieron suplementos de AOC (1.000 mg de vitamina C, 600 UI de vitamina E y 600 mg de ácido α-lipoico) o placebo (2.000 mg de talco) previo a dos pruebas realizadas con 7 días de diferencia. Prueba 1: AOC 120 y 90 minutos antes de una serie de ejercicio de resistencia (EEX) al 60% del consumo máximo de oxígeno (VO2max); prueba 2: AOC 120 y 90 minutos antes de una prueba de tolerancia oral a la glucosa (OGTT; 75 g de glucosa). Se obtuvieron datos de intercambio de gaseoso y muestras de sangre capilar cada 15 minutos durante ambas pruebas. Resultados: la suplementación con AOC aumentó los niveles de glucosa en reposo (p<0,05). Durante la prueba 1 (EEX), el AOC aumentó la oxidación de carbohidratos (CHOox) (p= 0,03), sin efecto en los niveles de glucosa en sangre. Durante la prueba 2 (OGTT), la suplementación con AOC no tuvo un efecto significativo en los parámetros de GM. Conclusión: Una suplementación aguda con AOC aumentó los niveles de glucosa en reposo y la CHOox durante EEX en sujetos sanos, sin efecto sobre el GM durante la OGTT.

Early predictors of prolonged intensive care utilization following liver transplantation.

INTRODUCTION: Creatinine, bilirubin, and fibrinolysis resistance are associated with multi-organ dysfunction and likely risk factors for prolonged intensive care unit (pICU) stay following liver transplantation (LT). We hypothesize postoperative day-1 (POD-1) labs will predict pICU. METHODS: LT recipients had clinical laboratories and viscoelastic testing with tissue plasminogen activator thrombelastography (tPA TEG) to quantify fibrinolysis resistance (LY30) on POD-1. pICU was defined as one week or longer in the ICU. Logistic regression was used to identify the relationship between POD-1 labs and pICU. RESULTS: Of 304 patients, 50% went to the ICU, with 15% experiencing pICU. Elevated creatinine (OR 6.6, P â€‹< â€‹0.001) and low tPA TEG LY30 (OR 3.7, P â€‹= â€‹0.004) were independent predictors of pICU after controlling for other risk factors. A 9-fold increase in the rate of 90-day graft loss (19% vs 2% p â€‹< â€‹0.001) was observed patients who had these risk factors for pICU. CONCLUSION: Elevated creatine and fibrinolysis resistance are associated with pICU and poor outcomes following LT.

The in-vitro influence of urea concentration on thromboelastrography in patients with and without end stage renal disease.

BACKGROUND: End stage renal disease (ESRD) is associated with platelet dysfunction but also thromboembolic complications. The specific role of increased blood urea nitrogen (BUN) on coagulation is unclear. We aimed to characterize thromboelastography (TEG) parameters from males and females with ESRD and normal kidney function and evaluate if exogenous urea in vitro reproduced those TEG differences. METHODS: We collected blood samples from 20 living kidney donors and 20 kidney recipients. TEG was performed without and with two increasing urea concentrations in vitro. TEG parameters were compared between recipients and donors. RESULTS: Blood from kidney recipients showed baseline increased maximum amplitude (MA) and shortened time to maximum amplitude (TMA) compared to donors. These differences were not confirmed in females. In all patients, BUN was inversely correlated with TMA (r = -0.342; p = 0.031). In males, BUN and creatinine concentrations showed a direct correlation with MA (0.583; p = 0.007) and an inverse correlation with TMA (r = -0.520; p = 0.019). Urea in vitro decreased R-time (p = 0.005) and increased LY30 (p = 0.009) in donors but not recipients. CONCLUSIONS: ESRD is associated with increased MA and decreased TMA on TEG. No change in MA was observed with increasing urea concentrations in vitro. Gender-specific variability in TEG parameters were observed.

Impact of a One-Stop Hematuria Clinic on Overall Survival and Bladder Tumor Recurrence.

BACKGROUND AND OBJECTIVE: One-stop clinics have emerged as a tool to optimize the therapeutic management of cancer patients. The main purpose of this study was to assess the role of the one-stop hematuria clinic (OSHC), as compared to a conventional clinic (CC), on the overall and disease-free survival of patients with bladder cancer. METHODS: A five-year follow-up retrospective and single-center study was conducted in patients with primary bladder tumor diagnosed between 2006 and 2015. The primary outcomes were five-year overall survival and one-year relapse rate. RESULTS: A total of 394 patients (160 in OSHC and 234 in CC) were included. No differences were observed in terms of age, sex, smoking habit or risk group between the OSHC and CC groups. The average times from first symptom to diagnosis (24.9 ± 29.1 vs. 100.7 ± 93.6 days) and from first symptom to treatment (70.2 ± 34.0 vs. 155.0 ± 102.9 days) were significantly lower in the OSHC group than in the CC group (p < 0.001 each). There was no significant difference in the five-year survival rate between OSHC and CC (103/160 vs. 150/234, respectively; p = 0.951), although the proportion of relapses during the first year was significantly lower in the OSHC group (35/139, 25.2%) than in the CC one (74/195, 38.0%; p = 0.02). CONCLUSIONS: OSHC significantly reduced the diagnosis and treatment times. The early-relapse rate was significantly lower in the OSHC group, although the five-year survival rate was similar.

Phytochemical screening and antibacterial assessment of two macroalgae Ulva papenfussi and Ulva nematoidea (Chlorophyta) against the bacterium Vibrio parahaemolyticus.

This study was conducted to determine whether the macroalgae Ulva papenfussi and Ulva nematoidea could be alternatives for preventing Litopenaeus vannamei vibriosis caused by the bacterium Vibrio parahaemolyticus. Phytochemical screening was performed on methanolic extracts to qualitatively determine the main groups of bioactive compounds, previous to an in vitro antibacterial test against V. parahaemolitycus. Phenols, polyphenols, flavonoids, and the high presence of carbohydrates were found in both macroalgae. U. papenfussi showed more presence of lipids and alkaloids than U. nematoidea . Macroalgae extracts prepared (v:v) with a 1:1 methanol: dichloromethane solvent was used for the in vitro test using the disc diffusion method (MDD). Filter paper discs impregnated with 1.0, 1.5, 2.0, 3.0, and 4.0 mg of the extracts showed antibacterial activity against V. Parahaemolitycus in a dose-dependent manner in both macroalgae. The inhibition zone varied significantly (p < 0.05) from 8.33 ± 0.12 to 11.41 ± 0.73 mm for 1 to 3 mg of extract levels, respectively. In conclusion, both macroalgae have antibacterial activity in their crude extracts against this bacteria. It is suggested to evaluate it as a feed additive for L. vannamei. This study is the first report on a phytochemical screening and antibacterial activity of these macroalgae against V. parahaemolyticus.

Histamine Recognition by Carbon Dots from Plastic Waste and Development of Cellular Imaging: Experimental and Theoretical Studies.

The present work highlights the sustainable approach for the transformation of plastic waste into fluorescent carbon dots (CDs) through carbonization and then they were functionalized with L-cysteine and o-phenylenediamine. CDs which were characterized by different analytical techniques such as X-ray diffraction (XRD), thermogravimetric analysis (TGA), Scanning electron microscopy (SEM), and transmission electron microscopy (TEM) are employed to recognize Cu2+, Fe2+, and Hg2+ ions. The results show that the fluorescence emission was considerably quenched, and it is consistent with the interference and Jobs plots. The detection limit was found to be 0.35µM for Cu(II), 1.38 µM for Hg(II), and 0.51µM Fe(III). The interaction of CDs with metal ions enhances the fluorescence intensity detecting histamine successfully. It shows that plastic waste-based CDs can be applied clinically to detect toxic metals and biomolecules. Moreover, the system was employed to develop the cellular images using Saccharomyces cerevisiae cells with the support of a confocal microscope. Furthermore, theoretical studies were performed for the naphthalene layer (AR) as a model for C-dots, then optimized its structure and analyzed by using the molecular orbital. The obtained TD-DFT spectra coincided with experimental spectra for CDs/M2+/histamine systems.

Caracterización de las fístulas enterocutáneas posoperatorias / Characterization of Postoperative Enterocutaneous Fistulas

Introducción: Las fístulas enterocutáneas representan una enfermedad grave que deben afrontar un gran número de cirujanos durante el ejercicio de la profesión. El tratamiento suele ser extremadamente complejo y siempre requiere de una intervención multidisciplinaria adaptada para cada caso en particular. Objetivo: Evaluar las características clínico-epidemiológicas y terapéuticas de las fístulas enterocutáneas posoperatorias. Métodos: Se realizó un estudio observacional, descriptivo, con recogida prospectiva de datos en el quinquenio 2013-2017. El universo fue de 28 pacientes diagnosticados con fístula enterocutánea posoperatoria y se usaron las variables: edad, sexo, carácter de la intervención, diagnóstico operatorio, tipo de fístula, tratamiento definitivo, complicaciones y pilares de tratamiento. Resultados: La edad media fue de 49 años. Las fístulas fueron más frecuentes en el sexo femenino (53,57 por ciento). El 78,57 por ciento de los pacientes fueron intervenidos con carácter de urgencia, y el 25 por ciento tuvieron un diagnóstico operatorio de oclusión intestinal mecánica por bridas seguida de la oclusión intestinal por tumor de colon izquierdo (17,86 por ciento). La hemicolectomía izquierda con anastomosis término-terminal (21,43 por ciento) y la resección intestinal con anastomosis término-terminal (17,86 por ciento) fueron los principales procedimientos quirúrgicos realizados. Conclusiones: Las fístulas de tipo II y de bajo gasto prevalecieron en la serie de casos en una media de tiempo que se corresponde con lo reportado en la literatura. La infección del sitio quirúrgico fue la complicación más observada y los pilares del tratamiento fueron cumplidos en la mayoría de los pacientes prevaleciendo el cierre espontáneo como tratamiento definitivo(AU)

Introduction: Enterocutaneous fistulas are a serious disease that a large number of surgeons must face during the practice of their profession. Their treatment is usually extremely complex and always requires a multidisciplinary intervention adapted to each particular case. Objective: To evaluate the clinical-epidemiological and therapeutic characteristics of postoperative enterocutaneous fistulas. Methods: An observational and descriptive study was performed, with prospective data collection, in the five-year period 2013-2017. The study universe was 28 patients diagnosed with postoperative enterocutaneous fistula. The following variables were used: age, sex, nature of the intervention, operative diagnosis, type of fistula, definitive treatment, complications and treatment cornerstones. Results: The mean age was 49 years. Fistulas were more frequent in the female sex (53.57 percent). 78.57 percent of the patients underwent emergency surgery, while 25 percent had an operative diagnosis of mechanical intestinal occlusion due to adherences, followed by intestinal occlusion due to left colon tumor (17.86 percent). Left hemicolectomy with end-to-end anastomosis (21.43 percent) and intestinal resection with end-to-end anastomosis (17.86 percent) were the main surgical procedures. Conclusions: Type II and low-output fistulas prevailed in the case series at a mean time that corresponds to that reported in the literature. Surgical site infection was the most frequently observed complication, while the treatment cornerstones were fulfilled in most patients, with spontaneous closure prevailing as a definitive treatment(AU)

Surgical gestures as a method to quantify surgical performance and predict patient outcomes.

How well a surgery is performed impacts a patient's outcomes; however, objective quantification of performance remains an unsolved challenge. Deconstructing a procedure into discrete instrument-tissue "gestures" is a emerging way to understand surgery. To establish this paradigm in a procedure where performance is the most important factor for patient outcomes, we identify 34,323 individual gestures performed in 80 nerve-sparing robot-assisted radical prostatectomies from two international medical centers. Gestures are classified into nine distinct dissection gestures (e.g., hot cut) and four supporting gestures (e.g., retraction). Our primary outcome is to identify factors impacting a patient's 1-year erectile function (EF) recovery after radical prostatectomy. We find that less use of hot cut and more use of peel/push are statistically associated with better chance of 1-year EF recovery. Our results also show interactions between surgeon experience and gesture types-similar gesture selection resulted in different EF recovery rates dependent on surgeon experience. To further validate this framework, two teams independently constructe distinct machine learning models using gesture sequences vs. traditional clinical features to predict 1-year EF. In both models, gesture sequences are able to better predict 1-year EF (Team 1: AUC 0.77, 95% CI 0.73-0.81; Team 2: AUC 0.68, 95% CI 0.66-0.70) than traditional clinical features (Team 1: AUC 0.69, 95% CI 0.65-0.73; Team 2: AUC 0.65, 95% CI 0.62-0.68). Our results suggest that gestures provide a granular method to objectively indicate surgical performance and outcomes. Application of this methodology to other surgeries may lead to discoveries on methods to improve surgery.

Efficient fluorescent recognition of ATP/GTP by a water-soluble bisquinolinium pyridine-2,6-dicarboxamide compound. Crystal structures, spectroscopic studies and interaction mode with DNA.

The new dicationic pyridine-2,6-dicarboxamide-based compound 1 bearing two N-alkylquinolinium units was synthesized, structurally determined by single-crystal X-ray diffraction, and studied in-depth as a fluorescent receptor for nucleotides and inorganic phosphorylated anions in pure water. The addition of nucleotides to 1 at pH = 7.0 quenches its blue emission with a selective affinity towards adenosine 5'-triphosphate (ATP) and guanosine 5'-tripohosphate (GTP) over other nucleotides such CTP, UTP, ADP, AMP, dicarboxylates and inorganic anions. On the basis of the spectroscopic tools (1H, 31P NMR, UV-vis, fluorescence), MS measurements and DFT calculations, receptor 1 binds ATP with high affinity (log K = 5.04) through the simultaneous formation of strong hydrogen bonds and π-π interactions between the adenosine fragment and quinolinium ring with binding energy calculated in 8.7 kcal mol-1. High affinity for ATP/GTP is attributed to the high acidity of amides and preorganized rigid structure of 1. Receptor 1 is an order of magnitude more selective for ATP than GTP. An efficient photoinduced electron transfer quenching mechanism with simultaneous receptor-ATP complexation in both the excited and ground states is proposed. Additionally, multiple spectroscopic studies and molecular dynamics simulations showed that 1 can intercalate into DNA base pairs.

Low viscoelastic clot strength, platelet transfusions, and graft dysfunction are associated with persistent postoperative ascites following liver transplantation.

INTRODUCTION: High output, persistent ascites (PA) is a common complication following liver transplant (LT). Recent work has identified that platelets help maintain endothelial integrity and can decrease leakage in pathological states. We sought to assess the association of PA following LT with platelet count and platelet function. METHODS: Clot strength (MA) is a measure of platelet function and was quantified using thrombelastography (TEG). Total drain output following surgery was recorded in 24-h intervals during the same time frame as TEG. PA was considered >1 L on POD7, as that much output prohibits drain removal. RESULTS: 105 LT recipients with moderate or high volume preoperative ascites were prospectively enrolled. PA occurred in 28%. Platelet transfusions before and after surgery were associated with PA, in addition to POD5 TEG MA and POD5 MELD score. Patients with PA had a longer hospital length of stay and an increased rate of intraabdominal infections. CONCLUSION: Persistent ascites following liver transplant is relatively common and associated with platelet transfusions, low clot strength, and graft dysfunction.

Fibrinolysis resistance after liver transplant as a predictor of early infection.

BACKGROUND: Infection is a leading cause of morbidity in liver transplant (LT). Considering that the fibrinolytic system is altered in sepsis, we investigated the relationship between fibrinolysis resistance (FR) and post-transplant infection. METHODS: Fibrinolysis was quantified using thrombelastography (TEG) with the addition of tPA to quantify FR. FR was defined as LY30 = 0% and stratified as transient if present on POD1 or POD5 (tFR), persistent (pFR) if present on both, or no FR (nFR) if absent. RESULTS: 180 LT recipients were prospectively enrolled. 52 (29%) recipients developed infection. 72 had tFR; 37 had pFR; and 71 had nFR. Recipients with pFR had significantly greater incidence of infections (51% vs. 26% tFR vs. 20% nFR, p = 0.002). pFR was independently associated with increased odds of post-transplant infection (adjusted OR 3.39, p = 0.009). CONCLUSIONS: Persistent fibrinolysis resistance is associated with increased risk of post-transplant infection.

Guía de práctica clínica para el manejo de la neumonía adquirida en la comunidad / Clinical Practice Guideline for the management of community-acquired pneumonia

Resumen La neumonía sigue siendo una de las principales causas de consulta y de hospitalización a la que, además de su un alto impacto en términos de morbilidad y mortalidad, se suma la actual problemática de resistencia a los antimicrobianos, por lo que establecer directrices que permitan su adecuado diagnóstico y tratamiento es de gran importancia para obtener mejores desenlaces clínicos y promover un uso racional de antibióticos en estos pacientes. La presente guía de práctica clínica (GPC) contiene recomendaciones basadas en la evidencia para el diagnóstico y tratamiento de la neumonía adquirida en la comunidad en adultos, las cuales fueron realizadas mediante el proceso de adaptación de GPC basadas en la evidencia para el contexto colombiano.

Abstract Pneumonia continues to be one of the main causes of consultation and hospitalization to which, besides its high impact on morbidity and mortality, the current problem of antimicrobial resistance is added; thus, establishing guidelines that allow its adequate diagnosis and treatment is of great importance to obtain better clinical outcomes and promote a rational use of antibiotics in these patients. This clinical practice guideline (CPG) contains evidence-based recommendations for the diagnosis and treatment of community-acquired pneumonia in adult population; these recommendations were made by means of the process of adaptation of evidence-based CPGs for the Colombian context.

MicroRNA networks in FLT3-ITD acute myeloid leukemia.

MiR-126 and miR-155 are key microRNAs (miRNAs) that regulate, respectively, hematopoietic cell quiescence and proliferation. Herein we showed that in acute myeloid leukemia (AML), the biogenesis of these two miRNAs is interconnected through a network of regulatory loops driven by the FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD). In fact, FLT3-ITD induces the expression of miR-155 through a noncanonical mechanism of miRNA biogenesis that implicates cytoplasmic Drosha ribonuclease III (DROSHA). In turn, miR-155 down-regulates SH2-containing inositol phosphatase 1 (SHIP1), thereby increasing phosphor-protein kinase B (AKT) that in turn serine-phosphorylates, stabilizes, and activates Sprouty related EVH1 domain containing 1 (SPRED1). Activated SPRED1 inhibits the RAN/XPO5 complex and blocks the nucleus-to-cytoplasm transport of pre-miR-126, which cannot then complete the last steps of biogenesis. The net result is aberrantly low levels of mature miR-126 that allow quiescent leukemia blasts to be recruited into the cell cycle and proliferate. Thus, miR-126 down-regulation in proliferating AML blasts is downstream of FLT3-ITD­dependent miR-155 expression that initiates a complex circuit of concatenated regulatory feedback (i.e., miR-126/SPRED1, miR-155/human dead-box protein 3 [DDX3X]) and feed-forward (i.e., miR-155/SHIP1/AKT/miR-126) regulatory loops that eventually converge into an output signal for leukemic growth.

Synergy of Venetoclax and 8-Chloro-Adenosine in AML: The Interplay of rRNA Inhibition and Fatty Acid Metabolism.

It is known that 8-chloro-adenosine (8-Cl-Ado) is a novel RNA-directed nucleoside analog that targets leukemic stem cells (LSCs). In a phase I clinical trial with 8-Cl-Ado in patients with refractory or relapsed (R/R) AML, we observed encouraging but short-lived clinical responses, likely due to intrinsic mechanisms of LSC resistance. LSC homeostasis depends on amino acid-driven and/or fatty acid oxidation (FAO)-driven oxidative phosphorylation (OXPHOS) for survival. We recently reported that 8-Cl-Ado and the BCL-2-selective inhibitor venetoclax (VEN) synergistically inhibit FAO and OXPHOS in LSCs, thereby suppressing acute myeloid leukemia (AML) growth in vitro and in vivo. Herein, we report that 8-Cl-Ado inhibits ribosomal RNA (rRNA) synthesis through the downregulation of transcription initiation factor TIF-IA that is associated with increasing levels of p53. Paradoxically, 8-Cl-Ado-induced p53 increased FAO and OXPHOS, thereby self-limiting the activity of 8-Cl-Ado on LSCs. Since VEN inhibits amino acid-driven OXPHOS, the addition of VEN significantly enhanced the activity of 8-Cl-Ado by counteracting the self-limiting effect of p53 on FAO and OXPHOS. Overall, our results indicate that VEN and 8-Cl-Ado can cooperate in targeting rRNA synthesis and OXPHOS and in decreasing the survival of the LSC-enriched cell population, suggesting the VEN/8-Cl-Ado regimen as a promising therapeutic approach for patients with R/R AML.