INDURG TRIAL Protocol: A Randomized Controlled Trial Using Indocyanine Green during Cholecystectomy in Acute Cholecystitis.

INTRODUCTION: Laparoscopic cholecystectomy is one of the most common gastrointestinal surgeries, and bile duct injury is one of its main complications. The use of real-time indocyanine green fluorescence cholangiography allows the identification of extrahepatic biliary structures, facilitating the procedure and reducing the risk of bile duct lesions. A better visualization of the bile duct may help to reduce the need for conversion to open surgery, and may also shorten operating time. The main objective of this study was to determine whether the use of indocyanine green is associated with a reduction in operating time in emergency cholecystectomies. Secondary outcomes are the postoperative hospital stay, the correct intraoperative visualization of the Calot's Triangle structures with the administration of indocyanine green, and the intraoperative complications, postoperative complications and morbidity according to the Clavien-Dindo classification. METHODS: This is a randomized, prospective, controlled, multicenter trial with patients diagnosed with acute cholecystitis requiring emergency cholecystectomy. The control group will comprise 220 patients undergoing emergency laparoscopic cholecystectomy applying the standard technique. The intervention group will comprise 220 patients also undergoing emergency laparoscopic cholecystectomy for acute cholecystitis with prior administration of indocyanine green. CONCLUSION: Due to the lack of published studies on ICG in emergency laparoscopic cholecystectomy, this study may help to establish procedures for its use in the emergency setting.

Modeling of intravenous caspofungin administration using an intestine-on-chip reveals altered Candida albicans microcolonies and pathogenicity.

Candida albicans is a commensal yeast of the human intestinal microbiota that, under predisposing conditions, can become pathogenic and cause life-threatening systemic infections (candidiasis). Fungal-host interactions during candidiasis are commonly studied using conventional 2D in vitro models, which have provided critical insights into the pathogenicity. However, microphysiological models with a higher biological complexity may be more suitable to mimic in vivo-like infection processes and antifungal drug efficacy. Therefore, a 3D intestine-on-chip model was used to investigate fungal-host interactions during the onset of invasive candidiasis and evaluate antifungal treatment under clinically relevant conditions. By combining microbiological and image-based analyses we quantified infection processes such as invasiveness and fungal translocation across the epithelial barrier. Additionally, we obtained novel insights into fungal microcolony morphology and association with the tissue. Our results demonstrate that C. albicans microcolonies induce injury to the epithelial tissue by disrupting apical cell-cell contacts and causing inflammation. Caspofungin treatment effectively reduced the fungal biomass and induced substantial alterations in microcolony morphology during infection with a wild-type strain. However, caspofungin showed limited effects after infection with an echinocandin-resistant clinical isolate. Collectively, this organ-on-chip model can be leveraged for in-depth characterization of pathogen-host interactions and alterations due to antimicrobial treatment.

Organ-on-chip models for infectious disease research.

Research on microbial pathogens has traditionally relied on animal and cell culture models to mimic infection processes in the host. Over recent years, developments in microfluidics and bioengineering have led to organ-on-chip (OoC) technologies. These microfluidic systems create conditions that are more physiologically relevant and can be considered humanized in vitro models. Here we review various OoC models and how they have been applied for infectious disease research. We outline the properties that make them valuable tools in microbiology, such as dynamic microenvironments, vascularization, near-physiological tissue constitutions and partial integration of functional immune cells, as well as their limitations. Finally, we discuss the prospects for OoCs and their potential role in future infectious disease research.

Mimicking the Intestinal Host-Pathogen Interactions in a 3D In Vitro Model: The Role of the Mucus Layer.

The intestinal mucus lines the luminal surface of the intestinal epithelium. This mucus is a dynamic semipermeable barrier and one of the first-line defense mechanisms against the outside environment, protecting the body against chemical, mechanical, or biological external insults. At the same time, the intestinal mucus accommodates the resident microbiota, providing nutrients and attachment sites, and therefore playing an essential role in the host-pathogen interactions and gut homeostasis. Underneath this mucus layer, the intestinal epithelium is organized into finger-like protrusions called villi and invaginations called crypts. This characteristic 3D architecture is known to influence the epithelial cell differentiation and function. However, when modelling in vitro the intestinal host-pathogen interactions, these two essential features, the intestinal mucus and the 3D topography are often not represented, thus limiting the relevance of the models. Here we present an in vitro model that mimics the small intestinal mucosa and its interactions with intestinal pathogens in a relevant manner, containing the secreted mucus layer and the epithelial barrier in a 3D villus-like hydrogel scaffold. This 3D architecture significantly enhanced the secretion of mucus. In infection with the pathogenic adherent invasive E. coli strain LF82, characteristic of Crohn's disease, we observed that this secreted mucus promoted the adhesion of the pathogen and at the same time had a protective effect upon its invasion. This pathogenic strain was able to survive inside the epithelial cells and trigger an inflammatory response that was milder when a thick mucus layer was present. Thus, we demonstrated that our model faithfully mimics the key features of the intestinal mucosa necessary to study the interactions with intestinal pathogens.

Lactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity.

Intestinal microbiota dysbiosis can initiate overgrowth of commensal Candida species - a major predisposing factor for disseminated candidiasis. Commensal bacteria such as Lactobacillus rhamnosus can antagonize Candida albicans pathogenicity. Here, we investigate the interplay between C. albicans, L. rhamnosus, and intestinal epithelial cells by integrating transcriptional and metabolic profiling, and reverse genetics. Untargeted metabolomics and in silico modelling indicate that intestinal epithelial cells foster bacterial growth metabolically, leading to bacterial production of antivirulence compounds. In addition, bacterial growth modifies the metabolic environment, including removal of C. albicans' favoured nutrient sources. This is accompanied by transcriptional and metabolic changes in C. albicans, including altered expression of virulence-related genes. Our results indicate that intestinal colonization with bacteria can antagonize C. albicans by reshaping the metabolic environment, forcing metabolic adaptations that reduce fungal pathogenicity.

Validation of the Grace Risk Score to Predict In-Hospital and 6-Month Post-Discharge Mortality in Patients with Acute Coronary Syndrome

Abstract Background The wide range of clinical presentations of acute coronary syndrome (ACS) makes it indispensible to use tools for risk stratification and for appropriate risks management; thus, the use of prognosis scores is recommended in the immediat clinical decision-making. Objective To validate the Global Registry of Acute Coronary Events (GRACE) score as a predictor of in-hospital and 6-month post-discharge mortality in a population diagnosed with ACS. Methods This is a prospective cohort study of consecutive patients diagnosed with ACS between May and December 2018. GRACE scores were calculated, as well as their predictive value for in-hospital and 6-month post-discharge mortality. The validity of the model was assessed by two techniques: discriminative power using the area under the receiver operating characteristic curve (AUC) and goodness-of-fit, using the Hosmer-Lemeshow (HL) test, at the 5% level of significance. Results A total of 160 patients were included, mean age 64 (±10.9) years; of which 60% were men. The risk model showed to have satisfactory ability to predict both in-hospital mortality, with an area under the curve (AUC) of 0.76 (95% confidence interval [CI], 0.57-0.95; p = 0.014), and 6-month post-discharge mortality, with AUC of 0.78 (95%CI, 0.62-0.94), p = 0.002. The HL test indicated good-fit for both models of the GRACE score. Conclusion In this study, the GRACE risk score for predicting mortality was appropriately validated in patients with ACS, with good discriminative power and goodness-of-fit. The results suggest that the GRACE score is appropriate for clinical use in our setting.

How to Learn a Complex Endoscopic Procedure: Knots in Transanal Endoscopic Surgery: Different Skill Among Surgeons.

PURPOSE: The intrarectal suture is considered a high technically complex procedure. The study's objectives were to assess the feasibility of making an intrarectal knot, through an in vitro study and assessing whether the video tutorial facilitates learning. MATERIALS AND METHODS: A detailed description of the technique. A comparative observational cross-sectional study in surgeons with no previous experience in intrarectal knots. RESULTS: Twenty-one of these 32 participants passed the intrarectal knot test without video tutorial (T1) (65.6%), and 26 (81.2%) after the video tutorial (T2) (P=0.26). The mean time taken to tie the knot fell from 74 seconds (SD=46) in T1 to 41 seconds (SD=41) in T2 (P<0.001). At T1, 26 participants (81.3%) described the technique as difficult, but only 7 (21.9%) at T2 (P<0.001). CONCLUSIONS: Performing the intrarectal knot suture is feasible. Despite the technical difficulty, the video tutorial is sufficient for surgeons to learn the technique.

Consecuencias de la toma de decisiones terapéuticas con base en el resultado del FAST en pacientes politraumáticos con fractura pélvica / Consequencies of therapeutic decision-making based on FAST results in trauma patients with pelvic fracture

Introducción: La exactitud del FAST disminuye notablemente en los pacientes politraumáticos con fractura pélvica. El objetivo es analizar las consecuencias de tomar decisiones terapéuticas basadas en el resultado del FAST en los pacientes politraumáticos con fractura de pelvis. Métodos: Estudio descriptivo de pacientes con politraumatismos mayores de 16 años que han ingresado en el área de críticos o que han fallecido previamente, con fractura pélvica. El resultado del FAST ha sido comparado con un valor realmente positivo o negativo según el resultado de la laparotomía o de la tomografía computarizada.Resultados: En 13 años, se ha incluido a 263 pacientes politraumáticos con fractura pélvica (ISS medio de 31; mortalidad 19%). El FAST tenía una sensibilidad del 65,2%, una especificidad del 69%, una tasa de falsos negativos del 34,8% y una tasa de falsos positivos del 30,9%. Los pacientes hemodinámicamente inestables tenían el doble de mortalidad que los pacientes estables (27% vs. 14%, p <0,05). Los pacientes con un FAST positivo tenían mayor mortalidad que los pacientes con FAST negativo (43% vs. 26%); 4 de 10 pacientes hemodinámicamente inestables con un FAST falsamente positivo que se sometieron a laparotomía exploradora innecesaria murieron por shock hipovolémico. La mortalidad se redujo del 60 al 20% asociando un packing preperitoneal. Conclusiones: La reducida eficacia del FAST en pacientes con fractura de pelvis nos obliga a cuestionarnos las consecuencias de la toma de decisiones terapéuticas con base en sus resultados. Los pacientes con FAST falsamente positivo tienen una mortalidad mayor, que se puede reducir aplicando un packing preperitoneal. (AU)

Introduction: FAST is essential to decide if trauma patients need laparotomy, but has a notably decrease in accuracy in patients with pelvic fracture. Our objective is to analyze the consequences of therapeutic decision-making based on the FAST results in trauma patients with pelvic fracture. Methods: Descriptive study that includes trauma patients older than 16 with a pelvic fracture admitted to the critical care area or who were fallecimiento. FAST result was compared with a true positive or negative value according to the results of laparotomy or abdominal CT. We recorded diagnosis and treatment of each injury and resolution of the case, detailing the cause of death, among all variables. Results: Over the 13–year period, we included 263 trauma patients with pelvic fracture, with a mean ISS of 31 and mortality of 19%. FAST had a sensitivity of 65.2%, specificity of 69%, false negative rate of 34.8% and false positive rate of 30.9%. Hemodynamically unstable patients died twice as many stable patients (27% vs. 14%, p <0.05). Patients with positive FAST died more than negative FAST (43% vs. 26%); and 4 of 10 hemodynamically unstable patients who underwent non therapeutic laparotomy after presenting a false positive FAST died from hypovolemic shock. The mortality rate fell from 60% to 20% when preperitoneal packing was performed before angio-embolization of the pelvis. Conclusion: FAST has low accuracy in polytraumatized patients with pelvic fracture. Patients with false positive FAST have higher mortality, which can be reduce notably applying a preperitoneal packing. (AU)

Consequencies of therapeutic decision-making based on FAST results in trauma patients with pelvic fracture.

INTRODUCTION: FAST is essential to decide whether trauma patients need laparotomy, but it has a notable decrease in accuracy in patients with pelvic fracture. Our objective is to analyze the consequences of therapeutic decision-making based on the FAST results in trauma patients with pelvic fracture. METHODS: Descriptive study that includes trauma patients older than 16 with a pelvic fracture admitted to the critical care area or who died. The FAST result was compared with a true positive or negative value according to the results of laparotomy or abdominal CT. We recorded diagnosis and treatment of each injury and resolution of the case, detailing the cause of death, among all variables. RESULTS: Over the 13-year period, we included 263 trauma patients with pelvic fracture, with a mean ISS of 31 and mortality of 19%. FAST had a sensitivity of 65.2%, specificity of 69%, false negative rate of 34.8% and false positive rate of 30.9%. Hemodynamically unstable patients died twice as many stable patients (27% vs 14%, P < .05). Patients with positive FAST died more than negative FAST (43% vs 26%); and 4 out of 10 hemodynamically unstable patients who underwent non-therapeutic laparotomy after presenting a false positive FAST died from hypovolemic shock. The mortality rate fell from 60% to 20% when preperitoneal packing was performed before angio-embolization of the pelvis. CONCLUSION: FAST has low accuracy in polytraumatized patients with pelvic fracture. Patients with false positive FAST have higher mortality, which can be reduced notably by applying preperitoneal packing.

Chemical Aspects of Human and Environmental Overload with Fluorine.

Over the last 100-120 years, due to the ever-increasing importance of fluorine-containing compounds in modern technology and daily life, the explosive development of the fluorochemical industry led to an enormous increase of emission of fluoride ions into the biosphere. This made it more and more important to understand the biological activities, metabolism, degradation, and possible environmental hazards of such substances. This comprehensive and critical review focuses on the effects of fluoride ions and organofluorine compounds (mainly pharmaceuticals and agrochemicals) on human health and the environment. To give a better overview, various connected topics are also discussed: reasons and trends of the advance of fluorine-containing pharmaceuticals and agrochemicals, metabolism of fluorinated drugs, withdrawn fluorinated drugs, natural sources of organic and inorganic fluorine compounds in the environment (including the biosphere), sources of fluoride intake, and finally biomarkers of fluoride exposure.

Activation of Neurogenesis in Multipotent Stem Cells Cultured In Vitro and in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3.

The inhibition of glycogen synthase kinase-3 (GSK-3) can induce neurogenesis, and the associated activation of Wnt/ß-catenin signaling via GSK-3 inhibition may represent a means to promote motor function recovery following spinal cord injury (SCI) via increased astrocyte migration, reduced astrocyte apoptosis, and enhanced axonal growth. Herein, we assessed the effects of GSK-3 inhibition in vitro on the neurogenesis of ependymal stem/progenitor cells (epSPCs) resident in the mouse spinal cord and of human embryonic stem cell-derived neural progenitors (hESC-NPs) and human-induced pluripotent stem cell-derived neural progenitors (hiPSC-NPs) and in vivo on spinal cord tissue regeneration and motor activity after SCI. We report that the treatment of epSPCs and human pluripotent stem cell-derived neural progenitors (hPSC-NPs) with the GSK-3 inhibitor Ro3303544 activates ß-catenin signaling and increases the expression of the bIII-tubulin neuronal marker; furthermore, the differentiation of Ro3303544-treated cells prompted an increase in the number of terminally differentiated neurons. Administration of a water-soluble, bioavailable form of this GSK-3 inhibitor (Ro3303544-Cl) in a severe SCI mouse model revealed the increased expression of bIII-tubulin in the injury epicenter. Treatment with Ro3303544-Cl increased survival of mature neuron types from the propriospinal tract (vGlut1, Parv) and raphe tract (5-HT), protein kinase C gamma-positive neurons, and GABAergic interneurons (GAD65/67) above the injury epicenter. Moreover, we observed higher numbers of newly born BrdU/DCX-positive neurons in Ro3303544-Cl-treated animal tissues, a reduced area delimited by astrocyte scar borders, and improved motor function. Based on this study, we believe that treating animals with epSPCs or hPSC-NPs in combination with Ro3303544-Cl deserves further investigation towards the development of a possible therapeutic strategy for SCI.

The Fluoro-Pauson-Khand Reaction in the Synthesis of Enantioenriched Nitrogenated Bicycles Bearing a Quaternary C-F Stereogenic Center.

A variety of enantioenriched fluorinated 6H-cyclopenta[c]pyridin-6-one bicycles, a scaffold present in several classes of monoterpenic alkaloids with varied biological activity, were synthesized in just five steps from simple aldehyde starting materials. The synthesis presented wide functional group tolerance and moderate to high yields and diastereoselectivities and could be carried out on a gram scale. These products were suitable for further transformations, such as hydrogenation and deprotection of the tert-butylsulfonyl protecting group.

Copper-Catalyzed Regioselective Synthesis of (E)-ß-Fluorovinyl Sulfones.

Organofluorine compounds are finding increasing application in a variety of fields such as pharmaceutical, agrochemical, and material sciences. However, given the scarcity of fluorine-containing natural products, advancement in this area depends almost entirely on the development of new synthetic methodologies. In this article, we present the synthesis of a series of previously undescribed (E)-ß-fluorovinyl sulfones via a simple copper-catalyzed addition of hydrogen fluoride to alkynyl sulfone starting materials in varying yields and E/Z selectivities. The hydrogenation of these products was also explored and compared with the hydrogenation of the related Z isomers. These new products may find interesting applications, given the versatility of vinyl sulfones in chemical synthesis and the unique properties of vinyl fluorides in biological settings.

Vinyl Fluorides: Competent Olefinic Counterparts in the Intramolecular Pauson-Khand Reaction.

Despite the great advances achieved in the Pauson-Khand reaction and the ever-increasing demand for fluorinated compounds, the use of vinyl fluorides as olefinic counterparts in the above-mentioned transformation had been completely overlooked. Herein, we describe, for the first time, the intramolecular Pauson-Khand reaction of enynes containing a vinyl fluoride moiety.

Morbidity after transanal endoscopic microsurgery: risk factors for postoperative complications and the design of a 1-day surgery program.

BACKGROUND: Transanal endoscopic microsurgery (TEM) is a minimally invasive procedure with low morbidity. The definition of risk factors for postoperative complications would help to identify the patients likely to require more care and surveillance in an ambulatory or 1-day surgery (A-OdS) program. The main endpoints are overall 30-day morbidity and relevant morbidity. The secondary objectives are to detect risk factors for complications, rehospitalization, and the time of occurrence of the postoperative complications, and to describe the adverse effects following hospitalization that the A-OdS program would avoid. METHODS: This is an observational study of consecutive patients undergoing TEM between June 2004 and December 2016. Overall and relevant morbidity based on the Clavien-Dindo (Cl-D) classification were recorded, as were demographic, preoperative, surgical, and pathology variables. Univariate and multivariate analyses of the risk factors were carried out. RESULTS: Six hundred and ninety patients underwent surgery, of whom 639 were included in the study. Overall morbidity rate was 151/639 patients (23.6%); the clinically relevant morbidity rate was 36/639 (Cl-D > II) (5.6%) and mortality 2/639 (0.3%). The most frequent complication was rectal bleeding, recorded in 16.9% (108/639 patients) and grade I in 86/108 patients (78. 9%). The period with the greatest risk of complications was the first 2 days. The rehospitalization rate after 48 h was 7%. The risk factors for complications were as follows: tumor size > 6 cm (OR 3.2, 95% CI 1.3-7.8), anti-platelet medication (OR 2.3, 95% CI 1.1-5.1), and surgeon's experience < 150 procedures (OR 2.0, 95% CI 1-4.1). CONCLUSIONS: TEM is a safe procedure. The low rates of morbidity, re-hospitalization, and postoperative complications in the first 2 days after surgery make the procedure suitable for A-OdS.

Chemistry of detrifluoroacetylatively in situ generated fluoro-enolates.

This review article comprehensively profiles all literature reports (2015-2018) related to the detrifluoroacetylative in situ generation of fluorine-containing enolates and their reactions with electrophilic reagents. The innovative facets of this unconventional methodology and its synthetic generality for the preparation of fluorine-containing compounds of high medicinal value are highlighted.

Aplicación del Shock Index como predictor de hemorragia en el paciente politraumático / The use of the Shock Index as a predictor of active bleeding in trauma patients

INTRODUCCIÓN: Las constantes vitales detectan la presencia de hemorragia al perder grandes cantidades de sangre, lo que comporta una gran morbimortalidad. El Shock Index (SI) es un parámetro que detecta el sangrado con puntos de corte de 0,9. El objetivo de este estudio es valorar si un punto de corte de ≥ 0,8 es más sensible para detectar sangrado oculto, permitiendo iniciar maniobras terapéuticas más precoces. MÉTODOS: Estudio analítico de validación del SI que incluye pacientes politraumatizados graves mayores de 16 años. Se registran constantes vitales y escalas predictivas de sangrado: SI, Assessment of Blood Consumption score y Pulse Rate Over Pressure score. Se analiza la relación del SI con 5 marcadores predictivos de sangrado: necesidad de transfusión masiva, embolización angiográfica, control del sangrado quirúrgico, muerte por shock hipovolémico y "sangrado activo" (presencia de al menos uno de los 4 marcadores anteriores en un paciente). RESULTADOS: Recogida prospectiva de datos de 1.402 pacientes politraumatizados durante 10 años. El Injury Severity Score medio fue de 20,9 (DE 15,8). Hubo una mortalidad del 10%. El SI medio fue de 0,73 (DE 0,29). En total presentaron "sangrado activo" el 18,7% de la serie. El SI medio en los pacientes con "sangrado activo" fue de 0,87, mientras que las constantes vitales estaban dentro de la normalidad. El área bajo la curva ROC del SI para el "sangrado activo" fue de 0,749. CONCLUSIONES: El SI con un punto de corte ≥ 0,8 es más sensible que aquel con el punto de corte ≥ 0,9 y permite iniciar maniobras de reanimación más precoces en los pacientes con sangrado oculto

INTRODUCTION: Vital signs indicate the presence of bleeding only after large amounts of blood have been lost, with high morbidity and mortality. The Shock Index (SI) is a hemorrhage indicator with a cut-off point for the risk of bleeding at 0.9. The aim of this study is to assess whether a cut-off of ≥ 0.8 is more sensitive for detecting occult bleeding, providing for early initiation of therapeutic maneuvers. METHODS: SI analytical validation study of severe trauma patients older than 16 years of age. Vital signs were recorded, and scales for predicting bleeding included: SI, Assessment of Blood Consumption score, and Pulse Rate Over Pressure score. The relationship between the SI and 5 markers for bleeding was analyzed: need for massive transfusion, angiographic embolization, surgical bleeding control, death due to hypovolemic shock, and the overall predictor "active bleeding" (defined as the presence of at least one of the 4 markers above). RESULTS: Data from 1.402 trauma patients were collected prospectively over a period of 10 years. The mean Injury Severity Score was 20.9 (SD 15.8). The mortality rate was 10%. The mean SI was 0.73 (SD 0.29). "Active bleeding" was present in 18.7% of patients. The SI area under the ROC curve for "active bleeding" was 0.749. CONCLUSIONS: An SI cut-off point ≥ 0.8 is more sensitive than ≥ 0.9 and allows for earlier initiation of resuscitation maneuvers in patients with occult active bleeding

Recent advances in the synthesis of functionalised monofluorinated compounds.

Over the past few years, we have tackled the synthesis of interesting monofluorinated organic molecules, such as: dihydronaphthalene derivatives, ß-fluoro sulfones and related carbonyl compounds, fluorohydrins and allylic alcohols. Overall, a wide range of modern synthetic techniques are covered in this feature article including transition-metal, photo- and organocatalysis, nucleophilic and electrophilic fluorinations, chiral auxiliaries and enantioselective catalysis.

The use of the Shock Index as a predictor of active bleeding in trauma patients. / Aplicación del Shock Index como predictor de hemorragia en el paciente politraumático.

INTRODUCTION: Vital signs indicate the presence of bleeding only after large amounts of blood have been lost, with high morbidity and mortality. The Shock Index (SI) is a hemorrhage indicator with a cut-off point for the risk of bleeding at 0.9. The aim of this study is to assess whether a cut-off of≥0.8 is more sensitive for detecting occult bleeding, providing for early initiation of therapeutic maneuvers. METHODS: SI analytical validation study of severe trauma patients older than 16 years of age. Vital signs were recorded, and scales for predicting bleeding included: SI, Assessment of Blood Consumption score, and Pulse Rate Over Pressure score. The relationship between the SI and 5 markers for bleeding was analyzed: need for massive transfusion, angiographic embolization, surgical bleeding control, death due to hypovolemic shock, and the overall predictor «active bleeding¼ (defined as the presence of at least one of the 4 markers above). RESULTS: Data from 1.402 trauma patients were collected prospectively over a period of 10 years. The mean Injury Severity Score was 20.9 (SD 15.8). The mortality rate was 10%. The mean SI was 0.73 (SD 0.29). «Active bleeding¼ was present in 18.7% of patients. The SI area under the ROC curve for «active bleeding¼ was 0.749. CONCLUSIONS: An SI cut-off point≥0.8 is more sensitive than≥0.9 and allows for earlier initiation of resuscitation maneuvers in patients with occult active bleeding.

Metal-Free and User-Friendly Regioselective Hydroxyfluorination of Olefins.

A simple, user-friendly, metal-free protocol for the regioselective anti-Markovnikov hydrofluorination of olefins using readily available and inexpensive reagents has been developed. This new approach displays a broader scope than previously reported methodologies and has been applied to the late-stage fluorination of a complex molecule, giving rise to a fluorosteroid derivative. The stereochemistry of the process has also been studied in some detail.