Rapid evolution of colistin resistance in a bioreactor model of infection of Klebsiella pneumoniae.

Colistin remains an important antibiotic for the therapeutic management of drug-resistant Klebsiella pneumoniae. Despite the numerous reports of colistin resistance in clinical strains, it remains unclear exactly when and how different mutational events arise resulting in reduced colistin susceptibility. Using a bioreactor model of infection, we modelled the emergence of colistin resistance in a susceptible isolate of K. pneumoniae. Genotypic, phenotypic and mathematical analyses of the antibiotic-challenged and un-challenged population indicates that after an initial decline, the population recovers within 24 h due to a small number of "founder cells" which have single point mutations mainly in the regulatory genes encoding crrB and pmrB that when mutated results in up to 100-fold reduction in colistin susceptibility. Our work underlines the rapid development of colistin resistance during treatment or exposure of susceptible K. pneumoniae infections having implications for the use of cationic antimicrobial peptides as a monotherapy.

Factores pronósticos de mortalidad a 30 días en neumonía por SARS-CoV-2 / Prognostic Factors for 30-day Mortality in SARS-CoV-2 Pneumonia

Introducción: SARS-CoV-2 ha causado millones de muertes a nivel global desde su primer caso reportado en China. En Guatemala existen pocos estudios que describan los factores pronósticos. Nuestro objetivo fue determinar los factores asociados de mortalidad a 30 días en pacientes con neumonía (Nm) por SARS-CoV-2 y construir un modelo predictor. Material y Métodos: Estudio retrospectivo en 144 sujetos en el Hospital Roosevelt de marzo a diciembre 2020 con criterios de Nm por SARS-CoV-2. Se revisó el expediente médico para datos clínicos y de laboratorio desde ingreso hasta alta hospitalaria o muerte. Resultados: Se evaluaron 105 hombres y 39 mujeres con media de edad 53 años. El 47% tenía comorbilidades como diabetes mellitus 2 e hipertensión arterial sistémica. Promedio de días de hospitalización: 13. Cuadros leves a moderados de Síndrome de Distrés Respiratorio Agudo (SDRA): 92%. Se indicó ventilación mecánica invasiva (VMI) a 46 pacientes. La mortalidad general fue 35%. Factores asociados a mortalidad a 30 días: edad ≥50 años, inicio de síntomas ≥7 días, SDRA severo, radio NL >4,4, recibir VMI, alteración en LDH y procalcitonina. Nuestro modelo mostró que los mejores predictores de mortalidad eran alteración en procalcitonina (OR: 4,45), recibir VMI (OR: 112) y días de estancia hospitalaria (OR: 1,12) con precisión de 91,5% y área bajo la curva de 94,4%. Conclusiones: Los factores pronósticos de mortalidad en pacientes guatemaltecos con Nm por SARS-CoV-2 son múltiples e incluyen rasgos demográficos, clínicos y serológicos; identificarlos y contar con un modelo pronóstico ayudará a brindar atención médica de precisión.

Introduction: SARS-CoV-2 has caused millions of deaths globally since its first case was reported in China. In Guatemala, few studies describe prognostic factors. Our objective was to determine the factors associated with 30 day mortality in patients with Pneumonia (Nm) due to SARS-CoV-2 and to build a predictor model. Material and Methods: Retrospective study in 144 subjects at Roosevelt Hospital from March to December 2020 with Nm criteria for SARS-CoV-2. The medical record was rviewed, obtaining clinical and laboratory data from admission to hospital discharge or death. Results: 105 men and 39 women with an average age of 53 years were evaluated. 47% had comorbidities, with type 2 diabetes mellitus and systemic arterial hypertension being common. The average number of days of hospitalization was 13. 92% had mild to moderate acute respiratory distress syndrome (ARDS). Invasive mechanical ventila-tion (IMV) was indicated for 46 patients. Overall mortality was 35%. The factors asso-ciated with 30-day mortality were age ≥50 years, the onset of symptoms ≥7 days, severe ARDS, N/L ratio >4.4, receiving IMV, alterations in LDH, and procalcitonin. Our model showed that the best predictors of mortality were altered procalcitonin (OR: 4.45), receiving IMV (OR: 112), and days of hospital stay (OR: 1.12) with precision of 91.5% and area under the curve of 94.4%. Conclusions: The prognostic factors of mortality in Guatemalan patients with Nm due to SARS-CoV-2 are multiple and include demographic, clinical and serological features; identifying them and having a prognostic model will help provide precision medical care.

TP53INP2-dependent activation of muscle autophagy ameliorates sarcopenia and promotes healthy aging.

Sarcopenia is a major contributor to disability in older adults, and thus, it is key to elucidate the mechanisms underlying its development. Increasing evidence suggests that impaired macroautophagy/autophagy contributes to the development of sarcopenia. However, the mechanisms leading to reduced autophagy during aging remain largely unexplored, and whether autophagy activation protects from sarcopenia has not been fully addressed. Here we show that the autophagy regulator TP53INP2/TRP53INP2 is decreased during aging in mouse and human skeletal muscle. Importantly, chronic activation of autophagy by muscle-specific overexpression of TRP53INP2 prevents sarcopenia and the decline of muscle function in mice. Acute re-expression of TRP53INP2 in aged mice also improves muscle atrophy, enhances mitophagy, and reduces ROS production. In humans, high levels of TP53INP2 in muscle are associated with increased muscle strength and healthy aging. Our findings highlight the relevance of an active muscle autophagy in the maintenance of muscle mass and prevention of sarcopenia.Abbreviation: ATG7: autophagy related 7; BMI: body mass index; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ROS: reactive oxygen species; TP53INP2: tumor protein p53 inducible nuclear protein 2; WT: wild type.

Pyridylpiperazine efflux pump inhibitor boosts in vivo antibiotic efficacy against K. pneumoniae.

Antimicrobial resistance is a global problem, rendering conventional treatments less effective and requiring innovative strategies to combat this growing threat. The tripartite AcrAB-TolC efflux pump is the dominant constitutive system by which Enterobacterales like Escherichia coli and Klebsiella pneumoniae extrude antibiotics. Here, we describe the medicinal chemistry development and drug-like properties of BDM91288, a pyridylpiperazine-based AcrB efflux pump inhibitor. In vitro evaluation of BDM91288 confirmed it to potentiate the activity of a panel of antibiotics against K. pneumoniae as well as revert clinically relevant antibiotic resistance mediated by acrAB-tolC overexpression. Using cryo-EM, BDM91288 binding to the transmembrane region of K. pneumoniae AcrB was confirmed, further validating the mechanism of action of this inhibitor. Finally, proof of concept studies demonstrated that oral administration of BDM91288 significantly potentiated the in vivo efficacy of levofloxacin treatment in a murine model of K. pneumoniae lung infection.

Characterization of pyridylpiperazine-based efflux pump inhibitors for Acinetobacter baumannii.

Objectives: In Acinetobacter baumannii, multidrug efflux pumps belonging to the resistance-nodulation-division (RND) superfamily result in decreased antibiotic susceptibility. Improving the activity of current antibiotics via efflux pump inhibitors (EPIs) represents an attractive alternative approach to control this bacterium. Pyridylpiperazines (PyrPips) are a new class of EPIs that can effectively inhibit the Escherichia coli RND efflux pump AcrAB-TolC and boost the activity of several antibiotics. Here we have evaluated and characterized whether the PyrPip chemical family is also able to boost antibiotic activity through inhibition of the RND efflux pumps in A. baumannii. Methods: Comparative structural modelling and docking, structure-activity relationship studies alongside molecular genetic approaches were deployed to improve, characterize and validate PyrPips' target. Results: We showed that two enhanced PyrPip EPIs are capable of rescuing the activity of different classes of antibiotics in A. baumannii. By expressing A. baumannii main efflux pumps (AdeB, AdeG and AdeJ) individually in E. coli recombinant strains, we could gain further insights about the EPIs' capacity to act upon each pump. Finally, we showed that PyrPip EPIs are mostly acting through AdeJ inhibition via interactions with two key charged residues, namely E959 and E963. Conclusions: Our work demonstrates that PyrPip EPIs are capable of inhibiting RND efflux pumps of A. baumannii, and thus may present a promising chemical scaffold for further development.

Optimization of pyridylpiperazine-based inhibitors of the Escherichia coli AcrAB-TolC efflux pump.

Multidrug-resistant Escherichia coli is a continuously growing worldwide public health problem, in which the well-known AcrAB-TolC tripartite RND efflux pump is a critical driver. We have previously described pyridylpiperazines as a novel class of allosteric inhibitors of E. coli AcrB which bind to a unique site in the protein transmembrane domain, allowing for the potentiation of antibiotic activity. Here, we show a rational optimization of pyridylpiperazines by modifying three specific derivatization points of the pyridine core to improve the potency and the pharmacokinetic properties of this chemical series. In particular, this work found that the introduction of a primary amine to the pyridine through ester (29, BDM91270) or oxadiazole (44, BDM91514) based linkers allowed for analogues with improved antibiotic boosting potency through AcrB inhibition. In vitro studies, using genetically engineered mutants, showed that this improvement in potency is mediated through novel interactions with distal acidic residues of the AcrB binding pocket. Of the two leads, compound 44 was found to have favorable physico-chemical properties and suitable plasma and microsomal stability. Together, this work expands the current structure-activity relationship data on pyridylpiperazine efflux pump inhibitors, and provides a promising step towards future in vivo proof of concept of pyridylpiperazines as antibiotic potentiators.

Splice variants of mitofusin 2 shape the endoplasmic reticulum and tether it to mitochondria.

In eukaryotic cells, different organelles interact at membrane contact sites stabilized by tethers. Mitochondrial mitofusin 2 (MFN2) acts as a membrane tether that interacts with an unknown partner on the endoplasmic reticulum (ER). In this work, we identified the MFN2 splice variant ERMIT2 as the ER tethering partner of MFN2. Splicing of MFN2 produced ERMIT2 and ERMIN2, two ER-specific variants. ERMIN2 regulated ER morphology, whereas ERMIT2 localized at the ER-mitochondria interface and interacted with mitochondrial mitofusins to tether ER and mitochondria. This tethering allowed efficient mitochondrial calcium ion uptake and phospholipid transfer. Expression of ERMIT2 ameliorated the ER stress, inflammation, and fibrosis typical of liver-specific Mfn2 knockout mice. Thus, ER-specific MFN2 variants display entirely extramitochondrial MFN2 functions involved in interorganellar tethering and liver metabolic activities.

Follow up of a cohort of patients with acute coronary syndrome without obstructive coronary disease. At a tertiary care center during 2019 and 2020

Introduction: 10% of acute myocardial infarctions occur with nonobstructive coronary arteries (MINOCA). These myocardial infarctions represent a group of conditions with less than 50% stenosis. The characteristics of the population with MINOCA in the region are unknown. The objective is to characterize the population with MINOCA and identify the factors associated with adverse outcomes. Materials and methods: this was an analytical cohort study which identified various char acteristics of patients with MINOCA at a tertiary care center in Pereira. From January 1, 2019, to December 31, 2020, 1,500 coronary arteriographies were reviewed; 292 met the angiographic criteria for MINOCA and, of these, 163 patients met the inclusion criteria. The primary outcome was a composite of hospitalization for angina/heart failure, reperfusion therapy, and death from cardiovascular causes and from any cause at six months and one year. Results: the median age was 64 years; 54% (n=88) were men. Arterial hypertension was the most prevalent comorbidity (n=100; 61.3%), and the most common electrocardiographic presenta tion was T wave inversion (29.7%; n=47). Altogether, 19.3% (n=28) and 25.5% (n=37) had some outcome at six months and one year. One-year mortality was 5.5%. On multivariate analysis, the initial troponin, moderate to severe aortic regurgitation and right bundle branch block were associ ated with the event. Conclusion: we have presented the Colombian study with the largest cohort of patients with MINOCA, identifying factors associated with adverse outcomes. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2742).

Mongolian Gerbils as an Animal Model of Wound Healing.

Corneal wound healing studies have been conducted for a long time and have helped to reduce suffering and develop treatments that contribute to improving patients' eye health. Historically, corneal healing has been studied in rodents such as mice and rats, but these models might not completely mimic human disorders. However, information on other rodents such as Mongolian gerbils (Meriones unguiculatus) is scant in corneal research. Here, we describe a technique to develop a novel animal model for studying corneal healing after photorefractive keratectomy. Due to the limited literature available on the cornea of M. unguiculatus, we also describe a histological analysis of the normal cornea. These research techniques can also be employed in the study of eye diseases because of the similarity between the corneas of Mongolian gerbils and humans in terms of genetics, anatomy, and physiology.

Welfare Indicators in Tilapia: An Epidemiological Approach.

Interest and concern about rearing methods and their impact on animal welfare have increased. Production evaluation is population-based, and animal welfare analysis should be similar. In fish, the most common welfare indicators are gill state, fin damage, and body condition. The objective of this study was to evaluate the feeding rate effect on the welfare indicators of Oreochromis niloticus using an epidemiological approach. Five growth stages (from 1.2 to 360 g) were studied using four feeding rates as treatments: underfeeding (80%), recommended feeding (100%), and two levels of overfeeding (120% and 140%). The evaluated welfare indicators include the presence of lesions in different body areas and fins, the decrease in body condition index, and their impact on biomass production. Incidence and relative risk were determined for each indicator. Statistically significant associations were found in the indicators of mortality, weight, body condition (K), and presence of evident damage in the caudal and anal fin in all stages. The results showed that the feed rate directly affects the welfare indicators and production. Mortality, weight reduction, K reduction, and caudal and anal fin damage incidence showed to be relevant indicators in all O. niloticus growing stages. As a result of this study, the epidemiological approach seems to be a valuable tool for production. A risk traffic light method is a proposal that could have great potential, with the suggested limits for WI's concerning the individuals present in the culture pond, allowing progressive evaluation and decision-making to correct risky situations.

Coordination of mitochondrial and lysosomal homeostasis mitigates inflammation and muscle atrophy during aging.

Sarcopenia is one of the main factors contributing to the disability of aged people. Among the possible molecular determinants of sarcopenia, increasing evidences suggest that chronic inflammation contributes to its development. However, a key unresolved question is the nature of the factors that drive inflammation during aging and that participate in the development of sarcopenia. In this regard, mitochondrial dysfunction and alterations in mitophagy induce inflammatory responses in a wide range of cells and tissues. However, whether accumulation of damaged mitochondria (MIT) in muscle could trigger inflammation in the context of aging is still unknown. Here, we demonstrate that BCL2 interacting protein 3 (BNIP3) plays a key role in the control of mitochondrial and lysosomal homeostasis, and mitigates muscle inflammation and atrophy during aging. We show that muscle BNIP3 expression increases during aging in mice and in some humans. BNIP3 deficiency alters mitochondrial function, decreases mitophagic flux and, surprisingly, induces lysosomal dysfunction, leading to an upregulation of Toll-like receptor 9 (TLR9)-dependent inflammation and activation of the NLRP3 (nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)-, and pyrin domain-containing protein 3) inflammasome in muscle cells and mouse muscle. Importantly, downregulation of muscle BNIP3 in aged mice exacerbates inflammation and muscle atrophy, and high BNIP3 expression in aged human subjects associates with a low inflammatory profile, suggesting a protective role for BNIP3 against age-induced muscle inflammation in mice and humans. Taken together, our data allow us to propose a new adaptive mechanism involving the mitophagy protein BNIP3, which links mitochondrial and lysosomal homeostasis with inflammation and is key to maintaining muscle health during aging.

Risk Factors of DAIR Failure and Validation of the KLIC Score: A Multicenter Study of Four Hundred Fifty-Five Patients.

Background: Debridement, antibiotic agents, and implant retention (DAIR) is a currently accepted approach for the treatment of early prosthetic joint infections (PJI). The success of a DAIR procedure has shown variable results throughout the published literature. Scoring systems such as the Kidney, Liver, Index surgery, Cemented prosthesis, and C-reactive protein value (KLIC) score for the selection of patients that are likely to benefit from DAIR have proved to be helpful in decision making. Our study aims to further validate the KLIC score using a large external multicentric cohort and to evaluate other risk factors for failure. Patients and Methods: A retrospective analysis of patients with an early acute PJI who were treated with DAIR and recorded in a database of eight Spanish university hospitals was performed. According to pre-operative variables of the KLIC study, patients were categorized into five groups: group A, ≤2 points; group B, 2.5-3.5 points; group C, 4-5 points; group D, 5.5-6.5 points; and group E, ≥7 points. Failure rates were compared between groups at 60 days and after 60 days of DAIR. Further variables for risk of failure were also analyzed. Results: A total of 455 patients with early acute PJI were included in the analyses. At 60 days, patients presenting with pre-operative elevated C-reactive protein serum levels, Staphylococcus aureus, and polymicrobial infections were associated with failure. Failure rates recorded were 12% for group A (n = 210), 18% for group B (n = 83), 26% for group C (n = 89), 24% for group D (n = 66), and 0% for group E (n = 7). Univariable analysis between consecutive groups of the KLIC score showed no differences for failure before 60 days of the DAIR procedure. Scheduled surgery and having the procedure performed by a specialized unit were also identified as important factors for DAIR success. Conclusions: Our results suggest the KLIC score was not useful for predicting failure in our cohort. Furthermore, our results indicate a specialized unit should conduct DAIR procedures.

Pyridylpiperazine-based allosteric inhibitors of RND-type multidrug efflux pumps.

Efflux transporters of the RND family confer resistance to multiple antibiotics in Gram-negative bacteria. Here, we identify and chemically optimize pyridylpiperazine-based compounds that potentiate antibiotic activity in E. coli through inhibition of its primary RND transporter, AcrAB-TolC. Characterisation of resistant E. coli mutants and structural biology analyses indicate that the compounds bind to a unique site on the transmembrane domain of the AcrB L protomer, lined by key catalytic residues involved in proton relay. Molecular dynamics simulations suggest that the inhibitors access this binding pocket from the cytoplasm via a channel exclusively present in the AcrB L protomer. Thus, our work unveils a class of allosteric efflux-pump inhibitors that likely act by preventing the functional catalytic cycle of the RND pump.

Imitation of ß-lactam binding enables broad-spectrum metallo-ß-lactamase inhibitors.

Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-ß-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential ß-lactamase stable ß-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.

Semi-Classical Discretization and Long-Time Evolution of Variable Spin Systems.

We apply the semi-classical limit of the generalized SO(3) map for representation of variable-spin systems in a four-dimensional symplectic manifold and approximate their evolution terms of effective classical dynamics on T*S2. Using the asymptotic form of the star-product, we manage to "quantize" one of the classical dynamic variables and introduce a discretized version of the Truncated Wigner Approximation (TWA). Two emblematic examples of quantum dynamics (rotor in an external field and two coupled spins) are analyzed, and the results of exact, continuous, and discretized versions of TWA are compared.

Demencia rápidamente progresiva, sobre el reporte de un caso de Creutzfeldt-Jakob / Rapidly Progressive Dementia, on a Creutzfeldt-Jakob Case Report

Resumen La enfermedad de Creutzfeldt-Jakob (ECJ) es una entidad neurodegenerativa, neuroselectiva y fatal con casi nulo reporte en México. Se presenta el caso de un paciente del sexo masculino de 40 años que inició de padecimiento con alteraciones de la memoria a corto plazo, episodios depresivos y labilidad emocional con tendencia a la irritabilidad, posteriormente se agregó desorientación espacial y disminución de fuerza del hemicuerpo izquierdo, lateropulsión en la marcha ipsilateral e insomnio, por lo cual fue ingresado al hospital por 40 días para abordaje diagnóstico. Durante su estancia hospitalaria se le realizaron diversos estudios siendo los más relevantes para el diagnóstico: resonancia magnética, la cual presentó "cintas corticales" e hiperintensidades en los núcleos de la base, ambos hallazgos altamente sugerentes de la patología, así como proteína 14-3-3 positiva, lo cual reafirmó el diagnóstico. Tras 15 meses del inicio de los síntomas neurológicos presentó un cuadro de neumonía adquirida en la comunidad, por lo cual fue admitido al hospital donde se diagnosticó absceso pulmonar y demencia rápidamente progresiva, finalmente el paciente falleció en el nosocomio por una sepsis de origen pulmonar, 18 meses después del inicio de los síntomas, no se realizó necropsia, esto de acuerdo con los estándares actuales del manejo de la enfermedad.

Abstract The Creutzfeldt-Jakob disease is a neurodegenerative, neuroselective and fatal entity, that is not usually reported in Mexico. We present a 40-year-old male patient who presents the onset of this illness, with short-term memory disorder, depressive episodes and emotional lability with a tendency to irritability. He also presents space disorientation, decreased strength of the left and lateral hemibody drive in the ipsilateral walk, and insomnia, for which he is admitted to the hospital during 40 days for diagnostic approach. Several studies were carried out during his hospital stay, the most relevant for the diagnosis: a magnetic resonance which presented "cortical ribboning" and hyperintensities in the nuclei of the base, both diagnosis highly suggested the pathology. The positive results to protein 14-3-3 reaffirmed the diagnosis. After 15 months of the onset of neurological symptoms, the patient presented symptoms of pneumonia, which lead to the hospitalization. During his stay, he presented a pulmonary abscess and rapid progressive dementia. The patient died in the hospital by a pulmonary sepsis 18 months after the onset of symptoms. No necropsy was performed, following the current standards for the disease management.

Efectos de la fragilidad en los resultados adversos de la cirugía cardiaca en ancianos / Effects of frailty on the adverse outcomes of cardiac surgery in the elderly

Resumen Introducción: la fragilidad es una condición del paciente anciano, caracterizada por un estado de vulnerabilidad para desenlaces adversos en salud, incluidos los causados por la cirugía cardíaca. Objetivo: establecer la prevalencia de fragilidad en el contexto prequirúrgico del anciano sometido a cirugía cardiaca y establecer el riesgo de desenlaces adversos otorgado por esta condición. Metodología: estudio analítico de cohorte que valoró la fragilidad en 66 pacientes ancianos sometidos a cirugía cardiaca mediante el fenotipo físico de fragilidad de Fried. Se realizó un seguimiento a 30 días, durante el cual se estableció la prevalencia de fragilidad y el riesgo otorgado por esta condición a los desenlaces adversos de la cirugía cardiaca. Resultados: la edad de los pacientes osciló entre los 60 y los 83 años; la mediana fue de 70,5 años. La prevalencia de la fragilidad fue del 31,8%. La fragilidad incrementó los siguientes desenlaces adversos postoperatorios: muerte (p 0,001), ventilación prolongada (p 0,001), uso prolongado de vasoactivos (p 0,001) e infección del sitio operatorio (p 0,004). El riesgo de mortalidad otorgado por la fragilidad fue más alto que el de los puntajes usuales de valoración como el EuroSCORE II (HR 5,49; IC95% 1,0-28,5 vs. HR 1,17 IC95% 1,0-1,29). Conclusión: la fragilidad es una condición frecuente en el paciente anciano sometido a cirugía cardiaca e incrementa el riesgo de eventos adversos, en especial el de mortalidad. Se recomienda incluir la medición de la fragilidad en el protocolo prequirúgico del paciente anciano.

Abstract Introduction: Frailty is a common condition in the elderly patient, and is noted for its vulnerability for adverse outcomes in health, including those caused by cardiac surgery. Objective: To establish the prevalence of frailty in the pre-surgical context of the elderly subjected to cardiac surgery, as well as to establish the risk of adverse outcomes due to this condition. Method: An analytical cohort study was performed in order to evaluate frailty in 66 elderly patients subjected to cardiac surgery, using the physical phenotype of frailty described by Fried. A follow-up was made at 30 days, during which the frailty prevalence was established, as well the risk of adverse outcomes of the cardiac surgery due to this condition. Results: The age of the patients varied between 60 and 83 years, with a median of 70.5 years. The prevalence of frailty was 31.8%. Frailty increased the following post-surgical adverse outcomes: death (P = .001), longer ventilation time (P = .001), prolonged use of vasoactive drugs (P = .001), and infection of the surgical site (P = .004). The mortality risk due to frailty was higher than that of the usual evaluation scores such as Euro SCORE II (HR 5.49; 95% CI; 1.0-28.5 vs. HR 1.17: 95% CI; 1.0-1.29). Conclusion: Frailty is a common condition in the elderly patient subjected to cardiac surgery, and increases the risk of adverse events, particularly, mortality. It is recommended to use measurements of frailty in the pre-surgical protocol of the elderly patient.

Early treatment of bilateral fungal keratitis with corneal cross-linking as adjuvant therapy.

Fungal keratitis is an ocular infection that has no standardized treatment. The etiological agents most frequently reported in the literature are Fusarium spp., Aspergillus spp., Alternaria spp. and Curvularia spp., related to injuries and Candida albicans related to contact lens wear. Here we present a case of bilateral fungal keratitis of a few days of evolution with insufficient response to antifungal pharmacological treatment and with early application of cross-linking in both eyes as an adjuvant therapy. A review of the current status of cross-linking for the treatment of corneal infections is presented.

Perfil de resistencia de la Salmonella sp durante un periodo de tres años en un hospital de Colombia / Resistance Profile of Salmonella SP During a Period of Three Years in a Hospital of Colombia / Perfil de resistência de Salmonella SP durante um período de três años em um hospital da Colômbia

Resumen Introducción: en Colombia, del 2000 al 2012, se describió un aumento progresivo en la resistência a betalactámicos y quinolonas en los aislamientos de Salmonella sp. A partir de esta fecha se desconoce la evolución de las tasas de resistencia en el país. El objetivo de este estúdio fue describir el perfil de suscep tibilidad durante el periodo 2014-2017 así como evaluar la asociación entre las características clínicas y sociodemográficas de la población con los patrones de resistencia de Salmonella sp. Materiales y méto dos: estudio de corte transversal del 2014 al 2017, realizado en la Fundación Cardioinfantil en mayores de 18 años, con aislamiento de Salmonella sp en cualquier tipo de muestra biológica. Resultados: se encontraron sesenta casos, ningún aislamiento fue resistente a quinolonas, uno mostró resistencia a ampicilina y uno se caracterizó como ; el 95 % tenia perfil de susceptibilidad usual. No se encontró asociación entre las variables estudiadas y la presencia de resistencia. Conclusión: los resultados pueden reflejar un cambio en el perfil de susceptibilidad de Salmonella sp en Colombia, con una disminución en la resistencia a betalactámicos y quinolonas a partir del 2014. Sin embargo, se requiere una mayor muestra poblacional para corroborar esta hipótesis.

Abstract Objective: In Colombia, from 2000 to 2012, a progressive increase in resistance to beta-lactams and quinolones was described in isolates of Salmonella As of this date, the evolution of resistance rates in the country is unknown. The objective of this study is to describe the susceptibility profile from 2014 to 2017, as well as to evaluate the association between the clinical and sociodemographic characteristics of the population with the resistance patterns of Salmonella Materials and methods: The study is a cross-sectional study between 2014 and 2017 at the Fundación Cardioinfantil, in patients over 18 years of age with Salmonella in any type of biologic sample. Results: The authors found 60 cases, no isolate was resistant to quinolones. One showed resistant to ampicillin, and añother one was characterized as amp-C; 95% had a usual susceptibility profile. No association was found between the variables studied and the presence of resistance. Conclusion: The results may reflect a change in the susceptibility profile of Salmonella in Colombia, with a decrease in resistance to beta-lactams and quinolones as of 2014; however, a larger population sample is required to corroborate this hypothesis.

Resumo Objetivo: Na Colômbia do ao 2000 ao 2012 se descreveu um aumento progressivo na resistência a beta-lactâmicos e quinolonas nos isolamentos de Salmonella sp. A partir desta data se desconhece a evolução das taxas de resistência no país. O objetivo deste estudo é descrever o perfil de susceptibilidade do ao 2014 ao 2017, assim como avaliar a associação entre as características clínicas e sociodemográficas da população com os patrões de resistência Salmonella sp. Materiais e métodos: Estudo de corte transversal do ano 2014 ao ao 2017 realizado na Fundación Cardioinfantil em maiores de 18 ao anos com isolamento de Salmonella sp, em qualquer tipo de amostra biológica. Resultados: se encontraram 60 casos, nenhum isolamento foi resistente a quinolonas, um mostrou resistência a ampicilina e um se caracterizou como AMP-C, o 95 % tinha perfil de susceptibilidade usual. Não se encontrou associação entre as variáveis estudadas e a presença de resistência. Conclusão: Os resultados podem refletir uma mudança no perfil de susceptibilidade de Salmonella sp. Na Colômbia, com uma diminuição na resistência a beta-lactâmicos e quinolonas a partir do año 2014, no entanto se requere uma maior amostra populacional para corroborar esta hipótese.

Knee Arthritis in Children: When Can It Be Safely Treated With Needle Joint Aspiration? A Large Children's Tertiary Hospital Study.

BACKGROUND: Early joint decompression associated to antibiotic therapy is the most important procedure to reduce joint damage in septic knee arthritis in children. Several joint decompression methods have been described such as arthrotomy with open debriding, arthroscopic drainage or needle joint aspiration. The aim of the present study was to determinate which patients with acute septic knee arthritis could be safely treated with needle joint aspiration. METHODS: Patients with an acute knee arthritis diagnosed between September 2003 and December 2013 in our children's tertiary hospital were retrospective review. All cases were initially treated with needle joint aspiration. Primary end-point was failure of joint aspiration. RESULTS: A total of 74 patients were included in the study. Forty-two (56.8%) were male and median age was 1.49 years. Mean delay between onset of symptoms and diagnosis was 3.6 days and in 25 (33.8%) cases patients needed more than 1 visit to the emergency room. Median C-reactive protein (CRP) value was 36.3 mg/L and was >20 mg/L in 59 (79.7%) cases. A total of 11 (14.9%) patients showed failure of the joint aspiration treatment between 3 and 21 days after initial joint aspiration. The stepwise forward logistic regression model only identified as independent predictor of joint aspiration failure an age older than 3 years old (odds ratio, 5.64; 95% confidence interval, 1.38-29.61; P=0.018). Joint aspiration did not fail in any patient younger than 12 months and neither in any patient younger than 3 years old with CRP value <20 mg/L. Otherwise, treatment failed in 38% of patients older than 3 years and in 16% of patients between 1 and 3 years with a CRP>20 mg/L. CONCLUSIONS: Septic knee arthritis treated with needle joint aspiration succeed in all patients younger than 1 year and in all patients between 1 and 3 years with a CRP<20 mg/L. Alternative treatment such as arthroscopy debridement should be early considered in patients older than 3 years and patients between 1 and 3 years with CRP>20 mg/L. LEVEL OF EVIDENCE: Level III.