An Analytical Solution for Saturable Absorption in Pharmacokinetics Models.

OBJECTIVE: The first-order absorption is a common model used in Pharmacokinetics. The absorption of some drugs follows carrier mediated transport. It has been proposed that the amount of drug available may saturate the transport mechanism resulting in an absorption slower than the one predicted by the first-order model. Saturable absorption has been modeled at the differential equation level by substituting the constant rate absorption by a Hill kinetics absorption. However, its exact solution is so far unknown. The goal of this is to know the exact solution of different Hill kinetic absorption models. METHODS: We start defining different absorption models and increasing then their complexity. The simplest case is the first-order absorption model and the most complex will be a generalized Hill kinetic absorption model. The differential equation of each model is integrated. RESULTS: The complexity of the models their solutions may be not expressed in a close-form, or in term of elementary functions. We obtain and discuss the exact solutions of the different Hill kinetics absorption models. To do that, the solutions are studied according to the possible values of the free parameters of the models. We show the differences between models through simulations. CONCLUSIONS: The knowledge of closed-form solutions allows to illustrate the differences between the different absorption models and minimizes the errors of numerical integration.

Phase I dose-escalation single centre clinical trial to evaluate the safety of infusion of memory T cells as adoptive therapy in COVID-19 (RELEASE).

BACKGROUND: Effective treatments are still needed to reduce the severity of symptoms, time of hospitalization, and mortality of COVID-19. SARS-CoV-2 specific memory T-lymphocytes obtained from convalescent donors recovered can be used as passive cell immunotherapy. METHODS: Between September and November 2020 a phase 1, dose-escalation, single centre clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD45RA- memory T cells containing SARS-CoV-2 specific T cells as adoptive cell therapy against moderate/severe cases of COVID-19. Nine participants with pneumonia and/or lymphopenia and with at least one human leukocyte antigen (HLA) match with the donor were infused. The first three subjects received the lowest dose (1 × 105 cells/kg), the next three received the intermediate dose (5 × 105 cells/kg) and the last three received the highest dose (1 × 106 cells/kg) of CD45RA- memory T cells. Clinicaltrials.gov registration: NCT04578210. FINDINGS: All participants' clinical status measured by National Early Warning Score (NEWS) and 7-category point ordinal scales showed improvement six days after infusion. No serious adverse events were reported. Inflammatory parameters were stabilised post-infusion and the participants showed lymphocyte recovery two weeks after the procedure. Donor microchimerism was observed at least for three weeks after infusion in all patients. INTERPRETATION: This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using convalescent CD45RA- memory T cells is feasible and safe. FUNDING: Clinical Trial supported by Spanish Clinical Research Network PT17/0017/0013. Co-funded by European Regional Development Fund/European Social Fund. CRIS CANCER Foundation Grant to AP-M and Agencia Valenciana de Innovación Grant AVI-GVA COVID-19-68 to BS.

Scipion PKPD: an Open-Source Platform for Biopharmaceutics, Pharmacokinetics and Pharmacodynamics Data Analysis.

PURPOSE: Biopharmaceutics examines the interrelationship of the drug's physical/chemical properties, the dosage form (drug product) in which the drug is given, and the administration route on the rate and extent of sys- temic drug absorption. Pharmacokinetics is the study of the movement of drugs in the body. It uses mathematical models to evaluate the movement of absorption, distribution, metabolism, and excretion (ADME) within an organism. Finally, Pharmacodynamics is the analysis of how these drugs af- fect that organism. Pharmacokinetics data normally comes in samples over time of the drug concentration either in plasma or in some specific tissue. Similarly, pharmacodynamics data comes normally in samples over time of some quantity of interest (biophysical quantity like temperature, blood pres- sure, etc.). The data is submitted to a non-parametric analysis, in which a description of the observed data is reported (e.g., the Area Under the Curve), or to a parametric analysis by fitting a model (normally based on differential equations) so that prediction about future events can be made. This paper aims to introduce Scipion PKPD, an open-source platform for data analysis of this kind in the three domains (Biopharmaceutics, Pharmacokinetics, and Pharmacodynamics). The platform implements the most popular models and is open to new ones. The platform provides almost 100 different high-level operations that we call protocols. METHODS: We have developed a Python module integrated into the work- flow engine Scipion. The plugin implements the numerical analysis and meta- data handling tools to address multiple problems (see Suppl. Material for a detailed list of the tasks solved). RESULTS: We illustrate the use of this package with an integrative exam- ple that involves all these areas. CONCLUSIONS: We show that the package successfully addresses these kinds of analyses. Scipion PKPD is freely available at https://github. com/cossorzano/scipion-pkpd .

Trans-olecranon fracture dislocations: How should we treat them?

BACKGROUND: Trans-olecranon fracture dislocations are the least frequent complex elbow instability. Proper surgical treatment should be performed to avoid postoperative complications. METHODS: A retrospective design study was performed. Patients that suffered from this injury, treated at our center from 2010 to 2016 were included. Fifteen patients were analyzed. Functional results were measured using DASH, MEPS and VAS scores. Average time from injury to first surgical treatment was 4.87 days. Radial head fracture was present in seven cases and coronoid process in three patients. Most frequent complication was hardware disturbances in five patients. Mean follow up was 3.65 years. RESULTS: Mean range of motion (ROM) was evaluated 1 year postoperatively: 129° flexion, 6° flexion contracture, and less than 5° deficit of pronation/supination. Clinical and functional results are encouraging, DASH 36.38, MEPS 100 and VAS 0.46. CONCLUSION: Trans-olecranon fracture dislocations could obtain functional range of movement, pain relief and good functional outcomes with a standardized protocol of surgical fixation. It is important to achieve proper ulnar fixation, focusing in reestablishing dorsal angulation, and also to treat radial head and coronoid injuries properly, if present.

A Signal Processing Approach to Pharmacokinetic Data Analysis.

The connection between pharmacokinetic models and system theory has been established for a long time. In this approach, the drug concentration is seen as the output of a system whose input is the drug administered at different times. In this article we further explore this connection. We show that system theory can be used to easily accommodate any therapeutic regime, no matter its complexity, allowing the identification of the pharmacokinetic parameters by means of a non-linear regression analysis. We illustrate how to exploit the properties of linear systems to identify non-linearities in the pharmacokinetic data. We also explore the use of bootstrapping as a way to compare populations of pharmacokinetic parameters and how to handle the common situation of using multiple hypothesis tests as a way to distinguish two different populations. Finally, we demonstrate how the bootstrap values can be used to estimate the distribution of derived parameters, as can be the allometric scale factors.

New Insights into Mechanical, Metabolic and Muscle Oxygenation Signals During and After High-Intensity Tethered Running.

High-intensity exercises including tethered efforts are commonly used in training programs for athletes, active and even sedentary individuals. Despite this, the knowledge about the external and internal load during and after this effort is scarce. Our study aimed to characterize the kinetics of mechanical and physiological responses in all-out 30 seconds (AO30) tethered running and up to 18 minutes of passive recovery. Additionally, in an innovative way, we investigated the muscle oxygenation in more or less active muscles (vastus lateralis and biceps brachii, respectively) during and after high-intensity tethered running by near-infrared spectroscopy - NIRS. Twelve physically active young men were submitted to AO30 on a non-motorized treadmill to determine the running force, velocity and power. We used wearable technologies to monitor the muscle oxygenation and heart rate responses during rest, exercise and passive recovery. Blood lactate concentration and arterial oxygen saturation were also measured. In a synchronized analysis by high capture frequency of mechanical and physiological signals, we advance the understanding of AO30 tethered running. Muscle oxygenation responses showed rapid adjustments (both, during and after AO30) in a tissue-dependence manner, with very low tissue saturation index observed in biceps brachii during exercise when compared to vastus lateralis. Significant correlations between peak and mean blood lactate with biceps brachii oxygenation indicate an important participation of less active muscle during and after high-intensity AO30 tethered running.

Outcomes of the PIRASOA programme, an antimicrobial stewardship programme implemented in hospitals of the Public Health System of Andalusia, Spain: an ecologic study of time-trend analysis.

OBJECTIVES: Inappropriate antimicrobial use favours the spread of resistance, and multidrug-resistant microorganisms (MDR) are currently of major concern. Antimicrobial stewardship programmes (ASPs) are essential for improving antibiotic use in hospitals. However, their impact on entire healthcare systems has not been thoroughly assessed. Our objective was to provide the results of an institutionally supported ASP involving 31 public hospitals in Andalusia, Spain. METHODS: We designed an ecologic time-series study from 1 January 2014 to 31 December 2017. Quarterly, data on indicators were collected prospectively, and feedback reports were provided. PIRASOA is an ongoing clinically based quality-improvement programme whose key intervention is the educational interview, regular peer-to-peer interventions between advisors and prescribers to reinforce the appropriate use of antibiotics. Seventy-two indicators were monitored to measure prescribing quality (inappropriate treatments), antimicrobial consumption (defined daily doses per 1000 occupied bed-days), incidence density of MDR per 1000 occupied bed-days and crude mortality rate associated with bloodstream infections. We used Joinpoint regression software to analyse the trends. RESULTS: The quality of antimicrobial prescribing improved markedly, and the inappropriate treatment rate was significantly lower, with quarterly percentage change (QPC) = -3.0%, p < 0.001. Total antimicrobial consumption decreased (QPC = -0.9%, p < 0.001), specifically carbapenems, amoxicillin/clavulanic acid, quinolones and antifungal agents, whereas antipseudomonal cephalosporin use increased. While the incidence of MDR showed a sustained decreasing trend (QPC = -1.8%; p 0.002), the mortality of patients with bloodstream infections remained stable (QPC = -0.2%, p 0.605). CONCLUSIONS: To date, the PIRASOA programme has succeeded in optimizing the use of antimicrobial agents and has had a positive ecologic result on bacterial resistance at level of an entire healthcare system.

[Mid-term complications of the monopolar, modular radial head prosthesis]. / Complicaciones a mediano plazo de la prótesis monopolar modular de cabeza radial.

INTRODUCTION: The objective of this study is to assess the type, frequency and severity of complications after the implantation of the modular monopolar radial head prosthesis. MATERIAL AND METHODS: Forty-seven patients with 48 radial head prostheses implanted between 2009 and 2017 were reviewed retrospectively. Patients were evaluated clinical and radiographically for a mean follow-up of 43.55 months (range: 12-89). RESULTS: The same type of prosthesis was implanted in every patient (Ascension Modular Radial Head). The average score in the Mayo Elbow Performance Score was 88.29 ± 9.9 points. During the follow-up, three patients (6.25%) suffered from continuous pain. Twelve cases (25.5%) showed radiological oversizing, though only five were symptomatic. Heterotopic ossification was detected in twenty-seven cases (57.4%). Eleven patients (23.4%) developed postoperative stiffness. Nineteen cases (40.42%) showed periprosthetic osteolysis, from which seven were symptomatic. Thirteen patients (27%) developed surgery-related complications: three cases of infection, four cases of symptomatic loosening, two neurapraxies, one instability and three cases of oversizing with associated stiffness. Nine patients (18.75%) required reintervention. DISCUSSION: Our study obtains a 27% of overall complications, mostly related to oversizing and prosthetic loosening, and 19% of reinterventions. These results are similar to those presented in previous studies, with variations depending on the time of follow-up. Further research is also required to evaluate long-term results and the potential progression of the radiographic findings. CONCLUSION: Taken together, these data stress the need for improvement in both the surgical technique and the design of the implants.

INTRODUCCIÓN: El objetivo de este estudio es evaluar el tipo, la frecuencia y la gravedad de las complicaciones después de la implantación de la prótesis monopolar modular de cabeza radial. MATERIAL Y MÉTODOS: Se revisaron retrospectivamente 47 pacientes con 48 prótesis de cabeza radial implantadas entre 2009 y 2017 durante una media de 43.55 meses (rango: 12-89). RESULTADOS: Se implantó el mismo tipo de prótesis en cada paciente (Ascension Modular Radial Head). La puntuación media obtenida en la clasificación Mayo Elbow Performance Score fue de 88.29 ± 9.9 puntos. Durante el seguimiento tres pacientes (6.25%) sufrieron dolor continuo. Doce casos (25.5%) mostraron sobredimensión radiológica, aunque sólo cinco fueron sintomáticos. Se detectó osificación heterotópica en 27 casos (57.4%), 11 pacientes (23.4%) desarrollaron rigidez postoperatoria, 19 casos (40.42%) mostraron osteólisis periprotésica, de los cuales siete fueron sintomáticos, 13 pacientes (27%) presentaron complicaciones: tres casos de infección, cuatro casos de aflojamiento sintomático, dos neuroapraxias, una inestabilidad y tres casos de sobredimensionamiento con rigidez asociada. Nueve pacientes (18.75%) fueron reintervenidos. DISCUSIÓN: Presentamos 27% de complicaciones globales, principalmente relacionadas con la sobredimensión y el aflojamiento protésico y 19% de reintervenciones. Estos resultados son similares a los descritos en estudios previos con variaciones en función del tiempo de seguimiento. Asimismo, se requieren nuevos estudios para evaluar los resultados a largo plazo y la posible progresión de los hallazgos radiográficos. CONCLUSIÓN: En conjunto, estos datos ponen de manifiesto la necesidad de mejoría tanto de la técnica quirúrgica como del diseño de los implantes.

[Installed Capacity Perception Survey for the Training of Residents Program in Orthopedics and Care Needs in Acute and Chronic Musculoskeletal Pathology in Mexico]. / Encuesta de Percepción en Capacidad Instalada para la Formación de Médicos Residentes en Ortopedia (Traumatología) y Necesidades de la Atención en Patología Musculoesquelética Aguda y Crónica en México. Primera Parte.

INTRODUCTION: It is essential that orthopaedic resident physicians be highly proficient in all aspects, considering the balance between supply, demand, need and context. Fundamental to identify the capacity and quality installed for their training in Mexico. MATERIAL AND METHODS: Observational Study, transverse, non-probabilistic sampling-conglomerates, in two phases. The instrument has 8 domains, 57 variables and 4,867 items. 60 graduate professors of 20 states, 50 hospital sites, 22 university programs. RESULTS: 1,038 years of experience (collective intelligence), 17 years of experience/teacher (01 to 50 years). Identified: acute pathology 30 (2 to 90%), chronic pathology 30 (5 to 96%), patients 15 years, 10 (3 to 30%), patients between 15 and 65 years, 47 (2 to 78%), patients 65 years, 20 (2 to 60%), number of beds/seat 20 (2 to 510), number of clinics 3 (1 to 48), number of surgical procedures/headquarters per year at the national level, was 960 (50 to 24,650). The national average per resident doctor is 362 surgeries/year with 1,450 surgical times/year. CONCLUSIONS: The needs and resources for the training of physicians specializing in orthopedics/traumatology are highly heterogeneous, so it should be adapted to the epidemiological needs of the region of influence, in an area of epidemiological transition. 62.2% expressed not having or have bad academic and scientific infrastructure at its headquarters, more than 50% without rotation overseas and 90% without regular scientific production.

INTRODUCCIÓN: Es fundamental que los médicos residentes de ortopedia (traumatología) sean altamente competentes en todos los aspectos, considerando el equilibrio entre la oferta, demanda, necesidad y contexto. Es primordial identificar la capacidad y calidad instalada para su formación en México. MATERIAL Y MÉTODOS: Estudio observacional, transversal, muestreo no probabilístico-conglomerados, en dos fases. El instrumento tiene ocho dominios, 57 variables y 4,867 ítems. Sesenta profesores de postgrado de 20 estados, 50 sedes hospitalarias, 22 programas universitarios. RESULTADOS: 1,038 años de experiencia (inteligencia colectiva), 17 años de experiencia/profesor (01 a 50 años). Se identificó: patología aguda 30 (2 a 90%), patología crónica 30 (5 a 96%), pacientes 15 años, 10 (3 a 30%), pacientes entre 15 y 65 años, 47 (2 a 78%), pacientes 65 años, 20 (2 a 60%), número de camas/sede 20 (2 a 510), número de consultorios 3 (1 a 48), el número de procedimientos quirúrgicos/sede al año a nivel nacional fue de 960 (50 a 24,650). La media nacional por médico residente es de 362 cirugías/año con 1,450 momentos quirúrgicos/año. CONCLUSIONES: Las necesidades y recursos para la formación de médicos especialistas en ortopedia/traumatología son en alto grado heterogéneos, por lo cual se debería adaptar a las necesidades epidemiológicas de la región de influencia, en un ámbito de transición epidemiológica. Sesenta y dos punto dos por ciento expresó no tener o tener deficiente infraestructura académica y científica en su sede, más de 50% sin rotación al extranjero y 90% sin producción científica regular.

[Shoulder arthroplasty complications: case report]. / Complicaciones de la artroplastía de hombro: reporte de un caso.

BACKGROUND: Infection and instability are the complications of prosthetic shoulder surgery of more difficult management. Instability builds up to half of the cases, while the fungal infection accounts for less than 1% of all and can cause severe damage to bone and soft tissue. METHODS: In this case clinical fungal infection by Candida parapsilosis is presented in a shoulder hemiarthroplasty indicated by a fracture of the proximal humerus. He received surgical treatment in two-stages and administration of fluconazole for eight weeks prior to the second surgical time. In revision surgery was placed a reverse prosthesis as definitive treatment; however, the patient suffered several episodes of dislocation in the postoperative period; a second revision prosthetic surgery was necessary to use more stable components. During this surgery, we extracted samples that were analyzed, obtaining negative results for infection. RESULTS: Now after three years of follow-up, the patient is well, no limitations in their daily work and has a Constant Score of 50.5. DISCUSSION: We report our experience in this exceptional situation. We know, this is one of the first cases where the fungal infection and dislocation prosthetics in the same patient meet. This situation is a challenge for the surgeon, which has to treat complications two practically at the same time; we do not have scientific evidence to establish a criterion unified for the treatment of complications after surgery for revision of arthroplasty of the shoulder, especially in reverse or mega-denture prosthesis.

ANTECEDENTES: La infección e inestabilidad se encuentran entre las complicaciones de más difícil manejo en la cirugía protésica de hombro. La inestabilidad acumula hasta la mitad de los casos, mientras que la infección por hongos representa menos de 1% del total de infecciones y pueden causar daño severo a nivel óseo y de partes blandas. MÉTODOS: En este caso clínico se presenta una infección fúngica por Candida parapsilosis en una hemiartroplastía de hombro indicada por una fractura de húmero proximal. Se dio tratamiento quirúrgico en dos tiempos y administración de fluconazol durante ocho semanas previo al segundo tiempo quirúrgico. En la revisión se colocó una prótesis reversa como tratamiento definitivo; sin embargo, el paciente sufrió varios episodios de luxación en el postoperatorio. Fue necesaria una segunda cirugía de revisión protésica para sustituir por componentes de mayor estabilidad. Durante la misma, se extrajeron muestras que fueron analizadas, obteniéndose resultados negativos para infección. RESULTADOS: Actualmente tras tres años de seguimiento, el paciente se encuentra bien, sin limitaciones en su labor diaria y tiene un Constant Score de 50.5. DISCUSIÓN: Reportamos nuestra experiencia en esta situación excepcional. A nuestro conocer, éste es uno de los primeros casos en los que la infección fúngica y la luxación protésica coinciden en un mismo paciente. Esta situación es un reto para el cirujano, el cual tiene que tratar las dos complicaciones prácticamente a la vez. No se dispone de una evidencia científica para establecer un criterio unificado para el tratamiento de las complicaciones tras cirugía de revisión de artroplastía de hombro, especialmente en la prótesis reversa o megaprótesis.

The relationship of Type 1 diabetes self-management barriers to child and parent quality of life: a US cross-sectional study.

AIM: Families of children and adolescents with Type 1 diabetes experience self-management challenges that negatively impact diabetes control. This study assesses whether self-management challenges are also associated with quality of life (QOL) for children and adolescents with Type 1 diabetes and their parents. METHODS: Children aged 8-12 years (n = 135), adolescents aged 13-16 years (n = 132) and their parents completed QOL assessments (diabetes-specific QOL from the PedsQL Diabetes Module or the Family Impact Module, both scaled 0-100) and a validated survey of up to six self-management barriers [PRISM; scaled 1 (low) to 5 (high)]. Regression coefficients were calculated to assess the association of self-management barriers with child and adolescent diabetes-specific QOL or parent QOL, including interaction effects to assess the stability of the associations. RESULTS: Mean duration of diabetes was 4.7 years for children and 6.1 years for adolescents. The majority of children and adolescents did not meet target values for glycaemic control. All barriers but one (Healthcare Team Interactions) were associated with lower diabetes-specific QOL for children and adolescents, as well as lower QOL for parents (all P < 0.05). Barrier scores that were 1 unit higher were associated with diabetes-specific QOL that was 3.7-5.1 points lower for children and 5.8-8.8 points lower for adolescents, as well as QOL that was 6.0-12.6 points lower for parents. Diabetes-specific QOL was most strongly associated with 'Denial of Disease and Its Consequences' for children and with 'Regimen Pain and Bother' for adolescents. Parent QOL was most strongly associated with 'Understanding and Organizing Care'. Associations were stable across numerous demographic and disease factors. CONCLUSIONS: Single-unit differences in self-management barrier scores are associated with clinically meaningful differences in QOL for children and parents. Interventions specifically tailored to address individual self-management barriers may improve both diabetes control and QOL.

Scaphoid-trapezium hereditary coalition. A case report. / Coalición carpiana escafotrapezoidea hereditaria. A propósito de un caso.

Carpal coalitions are relatively frequent between bones in the same carpal row. Coalitions between bones of different rows, however, are very uncommon. We present a case of bilateral intercarpal coalition between the trapezium and scaphoid as an incidental finding, confirming its hereditary origin since a parent has the same bilateral coalition.

Proposed clinical scale for the diagnosis of acute coronary syndrome in patients with an inconclusive electrocardiogram and myocardial injury biomarkers. / Propuesta de una escala clínica para el diagnóstico de síndrome coronario agudo en pacientes con electrocardiograma y biomarcadores de lesión miocárdica no concluyentes.

RATIONALE: Acute coronary syndrome (ACS) requires improved diagnostic accuracy through useful, safe and easy-to-apply tools. OBJECTIVES: To obtain an assessment scale for the diagnosis of ACS in patients with chest pain and nondiagnostic electrocardiogram and troponin concentrations. METHODS: A prospective cohort study included 286 patients treated in the emergency department for chest pain, with normal electrocardiogram and troponin levels. Using multiple logistic regression, we obtained the independent predictors for the diagnosis of ACS. The assessment scale's discriminative power was assessed with the area under the ROC curve. RESULTS: The diagnosis of ACS was confirmed in 103 patients (36%). The final predictive model included 3 endpoints: a history of coronary artery disease, hyperlipidaemia and a score≥6 points on the Geleijnse scale. The area under the ROC curve for the final model was 0.90 (95% confidence interval [95% CI] 0.85-0.93). A threshold of 5 points achieved a sensitivity of 76.7% (95% CI 68-84), a specificity of 91.8% (95% CI 87-95), a positive likelihood ratio of 9.36 (95% CI 5.70-15.40), a negative likelihood ratio of 0.25 (95% CI 18.00-36.00) and an overall diagnostic accuracy of 86.4% (95% CI 82-90). The predictive model was superior to the Geleijnse scale alone. CONCLUSIONS: The final scale showed good discriminative capacity for diagnosing ACS and could therefore be of interest for identifying ACS in emergency departments. Nevertheless, the scale needs to be validated in larger multicentre studies.

Scaphoid Fractures treated with a volar percutaneous approach. Analysis and results in 92 cases. / Fracturas de escafoides tratadas con técnica percutánea volar. Análisis y resultados de 92 casos.

OBJECTIVE: Herbert type B1 and B2 scaphoid fractures can be treated by orthopaedic treatment or surgery. The aim of this study is to analyse results and complications of scaphoid waist fractures treated using the percutaneous volar approach. MATERIAL AND METHOD: We present a retrospective study of 92 patients, treated in our institution from 2006 to 2016 using a volar percutaneous fixation. Mean Follow-up was 16 months (range 12-48). Injuries were classified using Hebert's classification, including B1 and B2 fracture types; the other fracture types following this classification system were excluded. Politrauma patients, dorsal approach, fractures associated with distal radius injuries, patients treated using another surgical technique and patients with non follow-up were also excluded. Functional results were evaluated using the DASH questionnaire. Consolidation was established as the presence of bony bridges crossing the fracture site on x-rays, associated with absence of pain. RESULTS: The average time to fracture healing was 6.6 weeks (range 5-11). After 12 months of follow-up, the average wrist range of motion was 70° of extension (range 58-75) and 70° of flexion (range 62-80). Regarding functional evaluation, the average DASH questionnaire score was 42. The most frequent complication was non-union in 4 cases (4.44%). Average surgical time was 25min. CONCLUSIONS: Volar percutaneous fixation is a simple and quick technique for a specialist surgeon, characterised by low morbidity and complication rates compared to ORIF and orthopaedic treatment, which accelerates the patient's functional recovery.

Diagnostic validity of hand gestures in chest pain of coronary origin. / Validez diagnóstica del lenguaje de las manos en el dolor torácico de origen coronario.

OBJECTIVES: To determine the frequency of 3 hand gestures by patients with chest pain and determine the diagnostic validity of the gestures in acute coronary syndrome. PATIENTS AND METHODS: A prospective study was conducted on 383 adult patients treated for chest pain in an emergency department. We observed certain hand gestures, previously referred to in the medical literature as characteristic of coronary pain (gesture 1: a clenched fist held over the sternal area or Levine's sign; gesture 2: open hand located over the same area; gesture 3: both hands placed in the centre of the chest), as well as other gestures. We analysed their association with the coronary origin of the pain. RESULTS: We confirmed the coronary origin of the pain in 164 (43%) patients (ACS group). The other 219 patients (57%) did not have a coronary origin for the pain (nonACS group). Eighty-nine percent of the patients identified their pain with one of the 3 classical gestures. The most frequent gesture was number 2, both overall (59%) and by group (60% ACS group; 57.5% nonACS group). There was no significant association between the type of gesture and the final diagnosis (P=.172). The greater specificity corresponded to Levine's sign (90%), followed by other gestures (86%) and gesture 3 (81%). CONCLUSIONS: Although 89% of the patients expressed their chest pain with one of the 3 manual gestures classically associated with coronary pain, none achieved sufficient diagnostic accuracy to be used as indicative of this type of pain.

Spotlight on the relevance of mtDNA in cancer.

The potential role of the mitochondrial genome has recently attracted interest because of its high mutation frequency in tumors. Different aspects of mtDNA make it relevant for cancer's biology, such as it encodes a limited but essential number of genes for OXPHOS biogenesis, it is particularly susceptible to mutations, and its copy number can vary. Moreover, most ROS in mitochondria are produced by the electron transport chain. These characteristics place the mtDNA in the center of multiple signaling pathways, known as mitochondrial retrograde signaling, which modifies numerous key processes in cancer. Cybrid studies support that mtDNA mutations are relevant and exert their effect through a modification of OXPHOS function and ROS production. However, there is still much controversy regarding the clinical relevance of mtDNA mutations. New studies should focus more on OXPHOS dysfunction associated with a specific mutational signature rather than the presence of mutations in the mtDNA.

Inhibición de la expresión del sistema agr de Staphylococcus aureus resistente a meticilina mediante el uso de polifenoles totales de hojas de aguacate mexicano (Persea americana var. drymifolia) / Inhibition of the expression of the agr system of methicillin-resistant Staphylococcus aureus by using total polyphenols of Mexican avocado leaves (Persea americana var. Drymifolia)

Resumen Introducción: La resistencia a los antibióticos por parte de las bacterias está provocando gran impacto negativo en la salud humana y en la producción animal. Actualmente, Staphylococcus aureus es considerada dentro de los seis principales grupos bacterianos con mayores reportes de aparición de resistencia a nivel mundial. Por otro lado, durante décadas las plantas de uso medicinal han sido fuente importante de compuestos bactericidas; sin embargo, también se ha empezado a documentar otras moléculas con otros mecanismos antimicrobianos, como es la inhibición de la percepción de quórum (anti-percepción de quórum (APQ)). En la medicina tradicional mexicana las hojas de aguacate mexicano (Persea americana var drymifolia) han sido empleadas para tratar diversos padecimientos que involucran infecciones bacterianas, por lo que es factible contenga compuestos que posean efectos antioxidantes, bactericidas y APQ, que ayuden a combatir las infecciones de cepas resistentes. De tal manera, que el objetivo de esta investigación fue determinar el efecto de los polifenoles totales de las hojas de Persea americana var. drymifolia y su actividad APQ sobre cepas de S. aureus resistentes a meticilina (MRSA). Métodos: Se obtuvieron los polifenoles presentes en las hojas de 18 cultivares de aguacate mexicano mediante extracción asistida por ultrasonido y fueron purificados en una columna de amberlita. Estos polifenoles fueron analizados funcionalmente y evaluados contra cepas de S. aureus MRSA para determinar su efecto APQ sobre el sistema denominado Agr. Resultados: Los polifenoles extraídos de las hojas de aguacate de raza mexicana exhiben una fuerte actividad bactericida. De los 18 cultivares probados, la variedad María Elena fue la que presentó el mayor efecto, exhibiendo una CMI de 116 µg∙mL-1 y un CMB de 133 µg∙mL-1 contra la cepa de MRSA µ3. Sin embargo, también logran inhibir los niveles de expresión del operón agr (P2 y P3) con respecto al gen constitutivo de rDNA 16S. De igual manera, los polifenoles mostraron una buena actividad antioxidante, además de que se logró identificar la presencia de flavonoides y saponinas. Discusión y Conclusión: Los polifenoles extraídos de las hojas de aguacate mexicano, exhiben principalmente actividad bactericida, pero también inhiben la expresión de genes asociados a la percepción de quórum de cepas de S. aureus MRSA. De igual manera, presentan una buena actividad antioxidante, lo que en conjunto puede ayudar a contrarrestar las infecciones con cepas resistentes de manera más eficiente. Por lo tanto, las hojas de aguacate mexicano son una fuente importante de metabolitos antioxidantes, bactericidas y APQ.

Antibody-Mediated Acute Vascular Rejection of Kidney Allografts: Fifteen-Year Follow-up.

BACKGROUND: Although acute vascular rejection (AVR) is associated with a high risk of graft loss, it remains unclear whether AVR with accompanied cellular or humoral rejection (AHR) has dissimilar outcomes. The aim of this study was to examine the association between subtypes of AVR and graft loss. METHODS: We assessed patients who provided biopsy samples for acute allograft rejection from 1998 to 2014. To investigate distinct rejection patterns, we retrospectively assessed rejection episodes with review of graft histology as well as donor-specific anti-HLA antibodies when available. RESULTS: A total of 1,004 patients were biopsied and included in the main analyses, of which 259 (32.87%) had acute biopsy-proven rejection. We identified three patterns of graft rejection defined according to the presence of peritubular capillaritis (ptc): a) T-cell-mediated acute vascular rejection if ptc free; b) humoral-mediated acute vascular rejection if ptc >0; and c) T-cell-mediated rejection if vasculitis = 0 and ptc = 0 (148 [57%], 70 [27%], and 41 [16%], respectively). At 5 years, graft survival was lower among patients with ptc-vascular rejection than those with T-cell vascular rejection (72.3% vs 83.2%; P = .010). T-cell-mediated rejection without vasculitis had similar survival compared with rejection absence (89.3% vs 8 9.2%; P = .698). Multivariate analysis adjusted by age and sex showed that risk of graft loss was higher in biopsies with high scores of glomerulitis (g2-g3); vasculitis (v2-v3), capillaritis (ptc2-ptc3), or interstitial inflammation (i2-i3). However, tubulitis and C4d were not statically significant. CONCLUSIONS: We conclude that antibody-mediated AVR involves a poorer prognosis than T-cell-mediated AVR. The presence of tubulitis does not seem to determine a poor long-term renal graft prognosis.

Seroprevalence and factors associated with equine herpesvirus type 1 and 4 in Spanish Purebred horses in Spain.

Equine herpesvirus type 1 (EHV-1) and type 4 (EHV-4) have a worldwide distribution and cause respiratory disease, abortion, neonatal death and myeloencephalopathy in susceptible horses. Given the scarcity of serological EHV-1/EHV-4 data in Spain, the objective of this cross-sectional study was to estimate the seroprevalence of EHV-1/EHV-4 and to identify potential horse-level and stud farm-level factors associated with EHV-1/EHV-4 in the breeding Spanish Purebred (SP) horse population in central Spain. Serum samples from 334 SP unvaccinated horses, collected between September 2011 and November 2013 at 30 stud farms, were tested using a commercially available EHV-1/EHV-4 antibody ELISA and seroneutralisation as the World Organisation for Animal Health reference confirmation test. Data on factors putatively associated with seropositivity to EHV-1/EHV-4 were collected via a questionnaire and examined using logistic regression analysis. EHV-1/EHV-4 seroprevalence in the SP breeding population in central Spain, standardised for the sex distribution of the reference horse population, was 53.9 per cent (95 per cent confidence interval 44.0 per cent to 63.8 per cent). Increasing age, southern location of the stud farm, temperate climate during the summer, and a smaller surface area used for breeding activities in the farm were associated with increased odds for EHV-1/EHV-4 seropositivity, whereas EHV-1/EHV-4 vaccination of other resident horses and separation of breeding mares from youngsters were protective factors.

Whooping cough in a renal transplant recipient.

Whooping cough is a respiratory infection with a severity that varies with age, immune status, and probably with other factors such as the degree of exposure and the virulence of the organism. The most frequent microorganism responsible for whooping cough is Bordetella pertussis. We present the case of a 62-year-old renal transplant recipient presenting with typical and severe manifestations of whooping cough caused by B. pertussis.