Concordancia entre las ecuaciones de estimación del filtrado glomerular y el aclaramiento de creatinina en orina de 4horas en pacientes críticos con trauma grave / Concordance between glomerular filtration rate estimation equations and 4-hour urinary creatinine clearance in critically ill patients with severe trauma

Antecedentes y objetivo: Cada vez hay más estudios que evidencian que las ecuaciones utilizadas para conocer la tasa de filtrado glomerular estimada (TFGe) no son adecuadas para los pacientes críticos en los que se producen continuas variaciones del filtrado glomerular (FG). El método más práctico para aproximarse al estudio del FG es el cálculo del aclaramiento de creatinina (ClCr) en periodos de recogida de orina variables. El objetivo del estudio fue observar el comportamiento de las ecuaciones empleadas para estimar el filtrado glomerular cuando se aplican a la subpoblación de pacientes críticos ingresados por trauma grave y comparar el ClCr en orina recogida en un periodo de 4horas (ClCr-4h). Material y métodos: Estudio observacional que incluye pacientes ingresados por trauma grave. Se calculó el ClCr-4h y se determinó la TFGe mediante las ecuaciones de Cockcroft-Gault, Jelliffe modificada, MDRD, t-MDRD y CKD-EPI. Los resultados se expresan referidos a superficie corporal (ml/min/1,73m2). Los análisis se realizaron con el software estadístico R versión 4.0.4. Resultados: Se incluyeron 85 pacientes. La edad mediana de los pacientes fue de 51años; 68 pacientes fueron varones (78,82%). El ClCr-4h ajustado a superficie corporal (ClCr-4h ml/min/1,73m2) medio fue de 84,5ml/min/1,73m2. Hallamos correlación estadísticamente significativa de ClCr-4h/1,73m2 con la TFGe por t-MDRD. Para ClCr-4h/1,73m2 mayores de 130ml/min/m2 la ecuación de Cockcroft-Gault identifica a los pacientes correctamente de una forma estadísticamente significativa. Conclusiones: El cálculo de ClCr en el entorno de UCI proporciona datos fiables del FG, no siendo adecuado el uso de ecuaciones estimativas.(AU)

Background and objective: There is a growing body of evidence that the equations used to estimate the glomerular filtration rate (GFR) are not suitable in critically ill patients, a population whose GFR fluctuates continuously. Glomerular filtration is usually estimated by measuring urine creatinine clearance (CrCl) at various time points. The aim of our study was to evaluate the performance of the most widely used GFR calculators in the subpopulation of critically ill patients admitted for severe trauma, and to compare the results against determinations of CrCl in urine collected over a 4-hour period (4h-CrCl). Material and methods: Observational study in patients hospitalized for severe trauma. We measured the 4h-CrCl and estimated GFR using the Cockcroft-Gault, modified Jelliffe, MDRD, t-MDRD, and CKD-EPI equations, adjusting the results for body surface area (BSA) (ml/min/1.73m2). Data were analysed using R version 4.0.4. Results: A total of 85 patients were included. Median age was 51years, and 68 were men (78.82%). The mean BSA-adjusted 4h-CrCl (4h-ClCr/1.73m2) was 84.5ml/min/1.73m2. We found that GFR estimated using the t-MDRD equation correlated significantly with 4h-CrCl/1.73m2. The Cockcroft-Gault equation correlated significantly with 4h-CrCl/1.73m2 when GFR was greater than 130ml/min/m2. Conclusions: In ICU patients, glomerular filtration can be reliably estimated by determining urine CrCl, but GFR calculators are not accurate in this population.(AU)

Concordance between glomerular filtration rate estimation equations and 4-hour urinary creatinine clearance in critically ill patients with severe trauma.

BACKGROUND AND OBJECTIVE: There is a growing body of evidence that the equations used to estimate the glomerular filtration rate (GFR) are not suitable in critically ill patients, a population whose GFR fluctuates continuously. Glomerular filtration is usually estimated by measuring urine creatinine clearance (CrCl) at various time points. The aim of our study was to evaluate the performance of the most widely used GFR calculators in the subpopulation of critically ill patients admitted for severe trauma, and to compare the results against determinations of CrCl in urine collected over a 4-h period (4h-CrCl). MATERIAL AND METHODS: Observational study in patients hospitalized for severe trauma. We measured the 4h-CrCl and estimated GFR using the Cockcroft-Gault, modified Jelliffe, MDRD, t-MDRD, and CKD-EPI equations, adjusting the results for body surface area (BSA) (ml/min/1.73m2). Data were analysed using R version 4.0.4. RESULTS: A total of 85 patients were included. Median age was 51 years, and 68 were men (78.82%). The mean BSA-adjusted 4h-CrCl (4h-ClCr/1.73m2) was 84.5 ml/min/1.73m2. We found that GFR estimated using the t-MDRD equation correlated significantly with 4h-CrCl/1.73m2. The Cockcroft-Gault equation correlated significantly with 4h-CrCl/1.73m2 when GFR was greater than 130ml/min/m2. CONCLUSIONS: In ICU patients, glomerular filtration can be reliably estimated by determining urine CrCl, but GFR calculators are not accurate in this population.

Evaluación de la salud sexual femenina en la consulta de Ginecología / Evaluation of female sexual health in routine gynaecological practice

Antecedentes: La disfunción sexual en la mujer es un problema multicausal y multidimensional, poco estudiado en la consulta de Ginecología. El objetivo de este trabajo fue estimar la calidad de vida sexual mediante el test de Índice de Función Sexual Femenina en las mujeres que acudieron a la consulta de Ginecología e identificar qué variables se asociaban a esta. Material y métodos: Estudio observacional descriptivo que incluye a las pacientes que acudieron a la consulta de Ginecología entre marzo y agosto 2019. Las pacientes rellenaron anónimamente el test de Índice de Función Sexual Femenina y se recogieron variables sociodemográficas y clínicas. Para establecer las características que pudieron estar asociadas con la calidad de la salud sexual se elaboró un modelo de regresión lineal múltiple. Resultados: Del total de pacientes encuestadas un 39,4% presentaban disfunción sexual con un valor medio del test de 27,2. Si excluimos pacientes que no tenían relaciones en el momento de la encuesta, este porcentaje descendió al 19,2%. La variable que más descendió el valor del Índice de Función Sexual Femenina fue la menopausia. Asimismo la edad y el tener 3 o más hijos también disminuyó el valor del test. Por el contrario, los estudios universitarios mejoraron significativamente el resultado de dicho test. Conclusiones: La disfunción sexual femenina es un problema multifactorial. Dado que afecta de forma significativa la salud global de las mujeres, se hace patente la necesidad de abordar la problemática en las consultas de Ginecología de manera real y eficaz.(AU)

Background and objective: Female sexual dysfunction is a multicausal and multidimensional pathology, often underestimated in gynaecology care. The aim of this study was to estimate the quality of sexual life using the Female Sexual Function Index test in women who attended the gynaecology practice and to identify which variables were associated with sexual dysfunction. Material and methods: Descriptive observational study that includes patients who attended routine gynaecology care between March and August 2019. The patients filled out the Female Sexual Function Index anonymously and sociodemographic and clinical variables were collected. To establish the characteristics that could be associated with the quality of sexual health, a multiple linear regression model was developed. Results: Of the total of patients surveyed, 39.4% presented sexual dysfunction with a mean value of 27.2. After excluding patients without sexual intercourse at the time of the survey, this percentage dropped to 19.2%. Menopause was the variable that most lowered the Female Sexual Function Index value. Likewise, age and having 3 or more children also decreased the test score. Nevertheless, having a university education significantly improved womeńs sexual health. Conclusions: Female sexual dysfunction is a multifactorial problem that greatly affects women's well-being. It is important to assess this problem in routine gynaecology care in order to improve female sexual and global health.(AU)

Specificities of clinical research in radiotherapy.

The aim of this review is to present the specificities of clinical research in radiation oncology. Objectives are similar to all research in oncology: to improve the efficacy and to decrease toxic effects. Phase III trials remain the main methodology to demonstrate an improvement in efficiency, but phase I-II and registers are also important tools to validate an improvement in the therapeutic index with new technologies. In this article we discuss the special features of end-points, selection of population, and design for radiation oncology clinical trials. Quality control of delivered treatments is an important component of these protocols. Financial issues are also discussed, in the particular context of France.

Profiling of a high mannose-type N-glycosylated lipase using hydrophilic interaction chromatography-mass spectrometry.

Many industrial enzymes exhibit macro- and micro-heterogeneity due to co-occurring post-translational modifications. The resulting proteoforms may have different activity and stability and, therefore, the characterization of their distributions is of interest in the development and monitoring of enzyme products. Protein glycosylation may play a critical role as it can influence the expression, physical and biochemical properties of an enzyme. We report the use of hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) to profile intact glycoform distributions of high mannose-type N-glycosylated proteins, using an industrially produced fungal lipase for the food industry as an example. We compared these results with conventional reversed phase LC-MS (RPLC-MS) and sodium dodecyl sulfate-polyacrylamide gel-electrophoresis (SDS-PAGE). HILIC appeared superior in resolving lipase heterogeneity, facilitating mass assignment of N-glycoforms and sequence variants. In order to understand the glycoform selectivity provided by HILIC, fractions from the four main HILIC elution bands for lipase were taken and subjected to SDS-PAGE and bottom-up proteomic analysis. These analyses enabled the identification of the most abundant glycosylation sites present in each fraction and corroborated the capacity of HILIC to separate protein glycoforms based on the number of glycosylation sites occupied. Compared to RPLC-MS, HILIC-MS reducted the sample complexity delivered to the mass spectrometer, facilitating the assignment of the masses of glycoforms and sequence variants as well as increasing the number of glycoforms detected (69 more proteoforms, 177% increase). The HILIC-MS method required relatively short analysis time (<30 min), in which over 100 glycoforms were distinguished. We suggest that HILIC(-MS) can be a valuable tool in characterizing bioengineering processes aimed at steering protein glycoform expression as well as to check the consistency of product batches.

Correction: Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

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[Diaphragmatic pacemaker dysfunction and utility of diaphragmatic ultrasonography]. / Disfunción de marcapasos diafragmático y utilidad de la ecografía diafragmática.

Patients with spinal cord injuries above the C5 vertebrae have a high risk of respiratory complications, and complete spinal cord injures can require support with mechanical ventilation. In selected patients, implantation of a diaphragmatic pacemaker offers the possibility of breathing without mechanical support and reduces respiratory complications, increasing the patient's independence. Ultrasonography is a simple and non-invasive technique that may be useful in the differential diagnosis of thoracic diseases. We present the case of a patient with a traumatic cervical spinal cord injury, who underwent diaphragmatic pacemaker implantation. The use of ultrasound allowed rapid and reliable diagnosis of device malfunction. M-mode diaphragmatic ultrasonography is a simple and non-invasive technique that can be incorporated into routine clinical practice to diagnose diaphragm movement disorders.

Birth-weight differences at term are explained by placental dysfunction and not by maternal ethnicity.

OBJECTIVE: To investigate the influence of ethnicity, fetal gender and placental dysfunction on birth weight (BW) in term fetuses of South Asian and Caucasian origin. METHODS: This was a retrospective study of 627 term pregnancies assessed at two public tertiary hospitals in Spain and Sri Lanka. All fetuses underwent biometry and Doppler examinations within 2 weeks of delivery. The influences of fetal gender and ethnicity, gestational age (GA) at delivery, cerebroplacental ratio (CPR) and maternal age, height, weight and parity on BW were evaluated by multivariable regression analysis. RESULTS: Fetuses born in Sri Lanka were smaller than those born in Spain (mean BW = 3026 ± 449 g vs 3295 ± 444 g; P < 0.001). Multivariable regression analysis demonstrated that GA at delivery, maternal weight, CPR, maternal height and fetal gender (estimates = 0.168, P < 0.001; 0.006, P < 0.001; 0.092, P = 0.003; 0.009, P = 0.002; 0.081, P = 0.01, respectively) were associated significantly with BW. Conversely, no significant association was noted for maternal ethnicity, age or parity (estimates = -0.010, P = 0.831; 0.005, P = 0.127; 0.035, P = 0.086, respectively). The findings were unchanged when the analysis was repeated using INTERGROWTH-21st fetal weight centiles instead of BW (log odds, -0.175, P = 0.170 and 0.321, P < 0.001, respectively for ethnicity and CPR). CONCLUSION: Fetal BW variation at term is less dependent on ethnic origin and better explained by placental dysfunction. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Epithelial-to-mesenchymal transition contributes to invasion in squamous cell carcinomas originated from actinic keratosis through the differentiated pathway, whereas proliferation plays a more significant role in the classical pathway.

BACKGROUND: Every actinic keratosis (AK) starts with atypia at the basal layers of the epidermis (AK I). Progression into invasive squamous cell carcinoma (iSCC) may occur following two main pathways, classical and differentiated. In the former, iSCC only occurs after involvement of the upper epidermal layers by atypical cells (AK III), while in the latter iSCC develops directly from AK I. In the anogenital mucosa, these two pathways are associated with differential expression of p53 and p16. OBJECTIVE: To explore differences between both pathways in the pathogenesis of AK, focusing on Ki67, p53, p16 and molecules that reveal epithelial-mesenchymal transition (EMT). METHODS: Tissue microarrays representative of superficial and deep portions of 80 consecutive iSCCs (53 DP/27CP) were studied immunohistochemically using antibodies against Ki67, p53, p16, vimentin, E-cadherin, ß-catenin and D2-40. The evaluation was performed by three researchers and the results compared to consensus. RESULTS: Invasive squamous cell carcinomas originated through the differentiated pathway exhibited significantly lower proliferative activity (Ki67) (30% vs 46%, P = 0.003) and significantly lower expression of vimentin (P < 0.001), E-cadherin (P < 0.001) and membranous ß-catenin (P < 0.001) than iSCCs developed through the classical pathway. The expression of E-cadherin and membranous ß-catenin was significantly correlated (Pearson's r = 0.386, Spearman's Rho < 0.001). There were no significant differences regarding the expressions of p53, p16 and D2-40. CONCLUSION: Epithelial-mesenchymal transition participates in transformation from AK I into iSCC (differentiated pathway), whereas a higher proliferative capacity facilitates intraepidermal extension in the classical pathway. Podoplanin, which is also involved in tumour invasion, does not seem to play a differential role in either pathway. Finally, the absence of differences in p53 and p16 expressions is at variance with other epithelia where the classical pathway is associated with human papillomavirus infection and can be explained by the fact that both AK pathways share identical mechanisms of actinic oncogenesis.

Detection of latent infections caused by Colletotrichum sp. in olive fruit.

AIMS: To set up a practical method to detect latent infections of Colletotrichum sp., the causal agent of olive anthracnose, on olives before the onset of disease symptoms. METHODS AND RESULTS: Freezing, sodium hydroxide (NaOH), ethanol and ethylene treatments were evaluated to detect latent infections on inoculated and naturally infected olive fruit by Colletotrichum sp. as non-hazardous alternatives to paraquat. Treatments were conducted using fruit of cultivars Arbequina and Hojiblanca. The disease incidence and T50 were calculated. Dipping in NaOH 0·05% solution and the paraquat method were the most effective treatments on both inoculated and naturally infected fruit, although the value of T50 was lower for the NaOH method than for the paraquat method in one of the experiments. Subsequently, the dipping time in NaOH 0·05% was evaluated. Longer dipping times in NaOH 0·05% were better than shorter ones in cultivar Arbequina, with 72 h being the most effective in cultivar Hojiblanca. CONCLUSIONS: NaOH solution is a practical method to detect latent infections of Colletotrichum sp. on immature olive fruit. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is relevant because we set up a viable, non-hazardous alternative to paraquat to detect latent infections of Colletotrichum sp. using NaOH. The use of NaOH is a simple and eco-friendly tool that allows the determination of the level of latent infections by Colletotrichum in olives. Therefore, our method will be useful in decision-making processes for disease management before the appearance of the first visible symptoms.

Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.

Impact of a tailored oral vitamin D supplementation regimen on serum 25-hydroxyvitamin D levels in early breast cancer patients: a randomized phase III study.

BACKGROUND: A minority of early breast cancer (EBC) patients treated with adjuvant or neoadjuvant chemotherapy have sufficient baseline vitamin D (vitD) level. This randomized phase III study assessed the safety and efficacy of a tailored, high-dose, oral vitD supplementation in restoring a normal 25-hydroxy vitD (25OHD) level in this population. PATIENTS AND METHODS: Participants received a 6-month conventional (C) vitD and calcium supplementation or a 6-month high-dose oral vitD regimen tailored on the deficiency (T) and a conventional calcium supplementation. The primary end point was the 6-month percentage of 25OHD serum level normalization. RESULTS: A total of 215 patients including 197 patients with vitD deficiency were recruited, and 195 patients were randomized (T, 100; C, 95). Compliance to the daily oral supplementation was 68.4% and 67% in the C and T arms, respectively. Discontinuous high-dose vitD compliance appeared higher in the T arm (77%). At 6 months, more patients presented with a normalized vitD level in the T arm (30% versus 12.6%; P = 0.003). Supplementation was well tolerated, and no significant difference in the treatment-related toxicity between the two arms was reported. Fifty-two patients without vitD normalization from the C arm switched to the T arm after 6 months. At 12 months, 44% of these patients achieved vitD normalization. CONCLUSION: A tailored high-dose oral vitD supplementation safely allows a higher percentage of the serum 25OHD level normalization compared with a conventional regimen in chemotherapy-treated EBC patients. As compliance to a daily oral supplementation remains poor in this setting, an adaptation of the treatment schedule is warranted. CLINICAL TRIAL NUMBER: NCT01480869.

Predictions for the [Formula: see text] decay.

We calculate the shape of the [Formula: see text] and [Formula: see text] invariant mass distributions in the [Formula: see text] and [Formula: see text] decays that are dominated by the [Formula: see text] resonance. The weak interaction part is the same for both processes and the hadronization into the different meson-baryon channels in the final state is given by symmetry arguments. The most important feature is the implementation of the meson-baryon final-state interaction using two chiral unitary models from different theoretical groups. Both approaches give a good description of antikaon-nucleon scattering data, the complex energy shift in kaonic hydrogen and the line shapes of [Formula: see text] in photoproduction, based on the two-pole scenario for the [Formula: see text]. We find that this reaction reflects more the higher mass pole and we make predictions of the line shapes and relative strength of the meson-baryon distributions in the final state.

[Cerebral artery thrombosis in pregnancy]. / Trombosis arterial cerebral en gestante.

A 28 year old woman, ASA I, who, in the final stages of her pregnancy presented with signs of neural deficit that consisted of distortion of the oral commissure, dysphagia, dysarthria, and weakness on the left side of the body. She was diagnosed with thrombosis in a segment of the right middle cerebral artery which led to an ischemic area in the right frontal lobe. Termination of pregnancy and conservative treatment was decided, with good resolution of the symptoms.

Relative Susceptibility of New Olive Cultivars to Spilocaea oleagina, Colletotrichum acutatum, and Pseudocercospora cladosporioides.

The evaluation of the relative susceptibility of new cultivars to the main diseases of a crop is a key point to consider prior to their release to the nursery industry. This study provides a rigorous characterization of the resistance of 15 new olive cultivars and their genitors ('Arbequina,' 'Frantoio,' and 'Picual') to the three main aerial diseases, peacock spot, anthracnose, and cercosporiosis caused by Spilocaea oleagina, Colletotrichum acutatum, and Pseudocercospora cladosporioides, respectively. To do so, developing leaves and detached green-yellowish fruit were inoculated in laboratory tests with S. oleagina and C. acutatum, respectively, using conidial suspensions of both pathogens. Additionally, a previously validated rating scale was used to assess the incidence of leaves with symptoms of S. oleagina or P. cladosporioides and the fruit rot incidence of C. acutatum in the trees for four years under field conditions. As a result, only two of the cultivars were susceptible to peacock spot, most likely because these new cultivars were previously screened for resistance to the disease on previous phases of the breeding program. Conversely, the 15 cultivars were susceptible or moderately susceptible to cercosporiosis. Five of the 15 new cultivars were classified as resistant to anthracnose, with four of them descendants of 'Frantoio' × 'Picual' crosses. In addition, the cultivars resistance to C. acutatum showed a negative linear correlation with the total phenols content of olive oil. This information regarding disease reaction of the new olive cultivars is essential for nursery industry and growers.

[Pyrimidal syndrome and anatomical variations as a cause of insidious sciatic pain]. / Síndrome piramidal y variaciones anatómicas como causa de dolor ciático insidioso.

The case is presented of a 42 year old woman who had been suffering a loss of strength in her left leg for six years. After an extensive diagnostic study, the pain was classified as of functional origin by a diagnosis of exclusion. Since then, the patient has tried all kind of drug treatments and conservative techniques without improvement. After an exhaustive study with inconclusive results, the case was discussed with the Orthopaedics Department, who performed an exploratory surgery, in which compression of the sciatic nerve due to an anatomical variation of the piriformis muscle was observed. Part of the muscle was resected during surgery and the sciatic nerve was freed, after which the patient experienced a great improvement.