Assessing tumor response to neoadjuvant chemoradiation in rectal cancer with rectoscopy and 18F-FDG PET/CT: results from a prospective series.

INTRODUCTION: rectoscopy and 18F-FDG PET/CT as a diagnostic algorithm for the assessment of tumor response in rectal cancer after neoadjuvant chemoradiation therapy (CRT) is very useful. MATERIAL AND METHODS: this was a prospective longitudinal study in patients with locally advanced rectal cancer treated with neoadjuvant CRT. Patients were assessed after CRT completion with a digital rectal examination, proctoscopy and 18F-FDG PET/CT. Patients were subdivided as clinical (cCR) or radiologic (rCR) responders and non-responders according to tumor response. Clinical and radiological re-assessment was compared with the surgical specimen. Pathological tumor regression (pCR) grade was determined according to Mandard's classification. Of the 68 patients included, 15 (22 %) presented pCR in the surgical specimen and tumor persistence (non-PCR) was detected in the remaining 53 (78 %). Clinical assessment (DRE+ rectoscopy) identified 15 patients as cCR and 53 as non-cCR, two were false positives and two were false negatives. The overall accuracy was 94 %. 18F-FDG PET/CT identified 18 patients as rCR and 50 as non-rCR, one was a false positive and four were false negatives. The overall accuracy was 92 %. A combination of clinical findings and 18F-FDG PET/CT resulted in an accuracy of 96 %. The combination of clinical findings + 18F-FDG PET/CT was able to correctly identify all cases of pCR, with the exception of one case that presented a tumor regression of 80 %. In this series, 18F-PET-CT and clinical assessment had excellent accuracies in differentiating PCR from non-PCR after CRT completion. PET-CT combined with clinical assessment had a better accuracy than both modalities independently. 18F-FDG PET/CT is a valid tool that complements the clinical assessment of tumor response.

Estimating Simultaneous Equation Models through an Entropy-Based Incremental Variational Bayes Learning Algorithm.

The presence of unaccounted heterogeneity in simultaneous equation models (SEMs) is frequently problematic in many real-life applications. Under the usual assumption of homogeneity, the model can be seriously misspecified, and it can potentially induce an important bias in the parameter estimates. This paper focuses on SEMs in which data are heterogeneous and tend to form clustering structures in the endogenous-variable dataset. Because the identification of different clusters is not straightforward, a two-step strategy that first forms groups among the endogenous observations and then uses the standard simultaneous equation scheme is provided. Methodologically, the proposed approach is based on a variational Bayes learning algorithm and does not need to be executed for varying numbers of groups in order to identify the one that adequately fits the data. We describe the statistical theory, evaluate the performance of the suggested algorithm by using simulated data, and apply the two-step method to a macroeconomic problem.

Long-Term Outcome After Conventional Two-Stage Hepatectomy Versus Tourniquet-ALPPS in Colorectal Liver Metastases: A Propensity Score Matching Analysis.

BACKGROUND: To compare the overall survival (OS) and disease-free survival (DFS) of Tourniquet-ALPPS (T-ALPPS) and conventional two-stage hepatectomy (TSH) in patients with colorectal liver metastases (CRLM). METHODS: A retrospective study from a prospectively collected database was performed between October 2000 and July 2016. TSH was performed before September 2011, after which time T-ALPPS became the technique of choice. A propensity score matching (PSM) was performed based on a 1:1 ratio with consideration of the following variables: number and size of metastases, bilobar disease presence, and chemotherapy received. RESULTS: Thirty-four patients received T-ALPPS; 41 patients received TSH. After PSM, 21 patients remained in each group, with 100% resectability in the T-ALPPS group and 90.5% resectability in the TSH group. The median OS for TSH was 41 months; for T-ALPPS, the median OS was 36 months (P = 0.925). The median DFS was 16 months in the TSH group; the median DFS was 9 months in the T-ALPPS group (P = 0.930). The 1-, 3-, and 5-year OS for TSH was 81%, 66.7%, and 23.8% vs. 76.2%, 57.1%, and 22.9% for T-ALPPS, respectively. The 1-, 3-, and 5-year DFS for TSH was 66.7%, 9.5%, and 5% vs. 44.6%, 11.1%, and 11.1% for T-ALPPS, respectively. The volume increase with T-ALPPS was superior to that with TSH (68% vs. 39%; P = 0.018). There were no differences in morbidity and mortality after stages 1 and 2. CONCLUSIONS: T-ALPPS produces a similar outcome to TSH, indicating that it could be a safe and effective alternative for curative hepatectomy for all patients.

Trans fatty acid intake is inversely related to total sperm count in young healthy men.

STUDY QUESTION: Is intake of fatty acids related to semen quality among young men? SUMMARY ANSWER: The intake of trans fatty acids is inversely related to total sperm count in healthy young men. WHAT IS KNOWN ALREADY: Spain has seen an increase in the proportion of calories consumed as fat over the same period that a downward trend in semen quality has been observed. In addition, rodent models suggest that trans fat intake may severely affect testicular function. STUDY DESIGN, SIZE, DURATION: Cross-sectional study of 209 men recruited between October 2010 and November 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: A group of 209 healthy young university students 18-23 years of age provided a semen sample and completed a previously validated food frequency questionnaire. The association between intake of fatty acids with semen quality parameters (sperm concentration, motility, morphology and total count) was assessed using multivariate linear regression. MAIN RESULTS AND THE ROLE OF THE CHANCE: Trans fatty acid intake was inversely related to total sperm count after adjusting for potential confounders (P, trend = 0.03). The multivariate adjusted mean (95% confidence interval) total sperm count in increasing quartiles of trans fat intake was 144 (110-190), 113 (87-148), 100 (18-130) and 89 (69-117). There also was an inverse association between cholesterol intake and ejaculate volume (P, trend = 0.04). No other statistically significant relations were observed. LIMITATIONS, REASONS FOR CAUTION: The cross-sectional design of the study limits causal inference, we cannot exclude the possibility of unmeasured confounding and there was insufficient statistical power to identify modest associations. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study, together with previous experimental work in rodents and biomarker studies among infertility patients, suggest that intake of trans fatty acids may be related to lower semen quality. Although the data provide further evidence that diet is a modifiable factor that could impact male fertility, it is not known whether the observed differences in sperm count translate into differences in fertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by The Seneca Foundation, Regional Agency of Science and Technology, grant no 00694/PI/04, Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (FIS), grant no PI10/00985, and grant P30 DK46200 from the National Institutes of Health. The authors have no competing interests to declare.

Anogenital distance of women in relation to their mother's gynaecological characteristics before or during pregnancy.

Animal models suggest that anogenital distance (AGD) at birth reflects androgen concentrations during in-utero development and predicts adult AGD. Several human observational studies show an association between menstrual cycle irregularities and a hyperandrogenic environment and that may result in a potential alteration of the female reproductive tract during in-utero development. This study examined associations between AGD of young women and their mother's gynaecological characteristics before or during pregnancy. This is cross-sectional study of 100 college-age volunteers in southern Spain. Physical and gynaecological examinations were conducted on the young women and they and their mothers completed epidemiological questionnaires on lifestyles and gynaecological history. Linear regression analysis was used to examine the association between AGD measurements (anus-fourchette (AGDAF) and anus-clitoris (AGDAC)) of women and their mother's gynaecological characteristics. Longer AGDAF was associated with the presence of mother's menstrual cycle irregularities before pregnancy (P=0.03). Longer female AGD has been related to excess androgen exposure in utero in toxicological studies. The current findings may be consistent with studies in which an association between menstrual cycle irregularities and an hyperandrogenic environment has been reported, which therefore may result in a potential modification of the female offspring's reproductive tract during in-utero development, including AGD. Rodent models suggest that perineal length at birth reflects male hormone concentrations (androgens) during in-utero development and predicts adult perineal length. Several human studies show a relationship between menstrual cycle irregularities and an excessive androgen environment. We hypothesize that androgen excess may result in a potential alteration of the female reproductive tract during in-utero development. Our aim was to examine associations between perineal length of young women and their mother's gynaecological characteristics before or during pregnancy. This is a study of 100 college-age volunteers in Southern Spain. Physical and gynaecological examinations were conducted on the young women and they and their mothers completed epidemiological questionnaires on lifestyles and gynaecological history. We used multivariate analyses to assess the association between perineal length of women and their mother's gynaecological characteristics. Longer perineal length was associated with the presence of mother's menstrual cycle irregularities before pregnancy. Longer female perineal length has been related to excess androgen exposure in utero in rodent studies. Our findings may be consistent with previous studies in which an association between menstrual cycle irregularities and an excess of androgen has been reported, which therefore may result in a potential modification of the female offspring's reproductive tract during in-utero development, including perineal length.

The NOMAD mini-apps: A suite of kernels from ab initio electronic structure codes enabling co-design in high-performance computing.

This article introduces a suite of mini-applications (mini-apps) designed to optimise computational kernels in ab initio electronic structure codes. The suite is developed from flagship applications participating in the NOMAD Center of Excellence, such as the ELPA eigensolver library and the GW implementations of the exciting, Abinit, and FHI-aims codes. The mini-apps were identified by targeting functions that significantly contribute to the total execution time in the parent applications. This strategic selection allows for concentrated optimisation efforts. The suite is designed for easy deployment on various High-Performance Computing (HPC) systems, supported by an integrated CMake build system for straightforward compilation and execution. The aim is to harness the capabilities of emerging (post)exascale systems, which necessitate concurrent hardware and software development - a concept known as co-design. The mini-app suite serves as a tool for profiling and benchmarking, providing insights that can guide both software optimisation and hardware design. Ultimately, these developments will enable more accurate and efficient simulations of novel materials, leveraging the full potential of exascale computing in material science research.

Dietary intake of antioxidant nutrients is associated with semen quality in young university students.

STUDY QUESTION: What are the associations between the dietary intake of antioxidant nutrients and semen parameters in young men? SUMMARY ANSWER: Our study suggests that some sperm parameters are sensitive to dietary intake of antioxidant nutrients. WHAT IS KNOWN ALREADY: A few reports have suggested that some dietary factors might be related to semen quality. However, the relationship between the intake of antioxidant nutrients and semen quality in young men remains unexplored. STUDY DESIGN, SIZE, DURATION: In this cross-sectional study, 215 young men were included between October 2010 and November 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthy university students with complete dietary and semen quality data were analyzed. Dietary intake was recorded using a validated food frequency questionnaire. The associations between the energy-adjusted nutrient intake of antioxidants in quartiles and the semen volume, sperm concentration, sperm motility, sperm morphology, total sperm count and total motile sperm count were assessed using multivariate linear regression. MAIN RESULTS AND THE ROLE OF CHANCE: Out of 240 students who contacted us, 223 (92.9%) were eligible to participate in this study, and 215 attended the clinical appointment. In the multivariate adjusted linear regression models, there was a positive association between dietary intakes of cryptoxanthin (P(trend) = 0.03), vitamin C (P(trend) = 0.04), lycopene (P(trend) = 0.03) and ß-carotene (P(trend) = 0.04) and total motile sperm count. The semen volume increased with higher intakes of vitamin C (P(trend) = 0.04). LIMITATIONS, REASONS FOR CAUTION: Only one sample of semen was taken for each subject. However, there are indications that one semen sample may be sufficient to characterize the semen quality of the individuals in epidemiological studies. Bias due to measurement errors may also occur since there is no perfect method to assess diet. However, any bias due to measurement error would be non-differential and would reduce, not increase, the strength of the associations. Although selection bias in cross-sectional studies might not always be ruled out, our subjects were university student volunteers who were rewarded for their participation and the study was not advertised as a fertility study. WIDER IMPLICATIONS OF THE FINDINGS: Previous articles in this area have focused mainly on men attending fertility clinics, thus our study brings generalizability to young men of the general population with unknown or untested fertility. Some of our results are in agreement with the previously reported papers.

Anogenital distance is related to ovarian follicular number in young Spanish women: a cross-sectional study.

BACKGROUND: In animals, anogenital distance (AGD) at birth reflects androgen levels during pregnancy and predicts adult AGD. Little is known about AGD in relation to female reproductive characteristics in humans, a question this study was designed to explore. METHODS: We used multiple linear and logistic regression analyses to model the relationships between adult female reproductive system characteristics (e.g. ovarian morphology, menstrual cycle) and two measures of AGD [anus-fourchette (AGD(AF)) and anus-clitoris (AGD(AC))] in 100 college-age volunteers in Spain. Ovarian morphology was classified as having < 6 or ≥ 6 follicles per ovary. RESULTS: Both AGD measures were positively associated with ovarian follicle number, with AGD(AF) being more strongly associated. Women in the upper tertile of the AGD(AF) and AGD(AC) distributions were more likely to have ≥ 6 ovarian follicles [OR: 6.0 (95% CI 2.0, 17.6) and 3.0 (95% CI 1.1, 8.6), respectively] compared to women in the lowest tertile. CONCLUSIONS: Increased follicular recruitment has been related to excess androgen exposure in utero in toxicological studies. Our results suggest that the androgenic environment during early fetal life may influence reproductive system development, including AGD, in human females.

The management of missed miscarriage in an outpatient setting: 800 versus 600 µg of vaginal misoprostol.

BACKGROUND: Many misoprostol regimens have been used to treat early pregnancy loss as an alternative to surgical evacuation, with differing adverse event and success rates. AIMS: This study sought to compare the effectiveness and adverse effects of 800 and 600 µg of misoprostol administered vaginally for the treatment of early pregnancy failure in an outpatient setting. METHODS: A retrospective, observational study of 946 women with a missed miscarriage <12 weeks' gestation was performed: 487 women received 800 µg (group 1) and 459 women received 600 µg (group 2) of vaginal misoprostol every 24 h for two days. The first follow-up was seven days after treatment. Women were asked about symptoms, and a transvaginal ultrasound was performed. If an incomplete miscarriage or gestational sac was still found, then an additional dose of intravaginal misoprostol was prescribed, and a second follow-up visit was arranged for seven days later. Surgical evacuation was scheduled for women who did not wish to continue medical treatment after the first or second follow-up visit. RESULTS: The total rate of complete miscarriage was 90.6% after 800 µg and 87.8% after 600 µg of intravaginal misoprostol. The percentage of women who underwent surgical evacuation after medical treatment was 9.4% for group 1 and 12.2% for group 2. CONCLUSIONS: Complete uterine evacuation after a missed miscarriage was effectively induced by both 600 and 800 µg of misoprostol. The overall success of medical treatment with intravaginal misoprostol demonstrates that the treatment is safe in an outpatient setting.

A hyper-matheuristic approach for solving mixed integer linear optimization models in the context of data envelopment analysis.

Mixed Integer Linear Programs (MILPs) are usually NP-hard mathematical programming problems, which present difficulties to obtain optimal solutions in a reasonable time for large scale models. Nowadays, metaheuristics are one of the potential tools for solving this type of problems in any context. In this paper, we focus our attention on MILPs in the specific framework of Data Envelopment Analysis (DEA), where the determination of a score of technical efficiency of a set of Decision Making Units (DMUs) is one of the main objectives. In particular, we propose a new hyper-matheuristic grounded on a MILP-based decomposition in which the optimization problem is divided into two hierarchical subproblems. The new approach decomposes the model into discrete and continuous variables, treating each subproblem through different optimization methods. In particular, metaheuristics are used for dealing with the discrete variables, whereas exact methods are used for the set of continuous variables. The metaheuristics use an indirect representation that encodes an incomplete solution for the problem, whereas the exact method is applied to decode the solution and generate a complete solution. The experimental results, based on simulated data in the context of Data Envelopment Analysis, show that the solutions obtained through the new approach outperform those found by solving the problem globally using a metaheuristic method. Finally, regarding the new hyper-matheuristic scheme, the best algorithm selection is found for a set of cooperative metaheuristics ans exact optimization algorithms.

Relationships between heavy metal concentrations in three different body fluids and male reproductive parameters: a pilot study.

BACKGROUND: Animal studies have shown the reproductive toxicity of a number of heavy metals. Very few human observational studies have analyzed the relationship between male reproductive function and heavy metal concentrations in diverse biological fluids. METHODS: The current study assessed the associations between seminal and hormonal parameters and the concentration of the 3 most frequent heavy metal toxicants (lead, cadmium and mercury) in three different body fluids. Sixty one men attending infertility clinics that participated in a case-control study to explore the role of environmental toxins and lifestyles on male infertility were analyzed. Concentration of lead, cadmium and mercury were measured in blood and seminal plasma and whole blood using anodic stripping voltammetry and atomic absorption spectrophotometry. Serum samples were analyzed for follicle-stimulating hormone, luteinizing hormone and testosterone. Semen analyses were performed according to World Health Organization criteria. Mann-Whitney test and Spearman's rank correlations were used for unadjusted analyses. Multiple linear regression models were performed controlling for age, body mass index and number of cigarettes per day. RESULTS: There were no significant differences between cases and controls in the concentrations of heavy metals in any of the three body fluids. In multivariate analyses using all subjects no significant associations were found between serum hormone levels and metal concentrations. However there was a significant positive association between the percentage of immotile sperms and seminal plasma levels of lead and cadmium. CONCLUSIONS: Our results suggest that the presence of lead and cadmium in the reproductive tract of men may be related to a moderate alteration of their seminal parameters.

Improving prediction of COVID-19 evolution by fusing epidemiological and mobility data.

We are witnessing the dramatic consequences of the COVID-19 pandemic which, unfortunately, go beyond the impact on the health system. Until herd immunity is achieved with vaccines, the only available mechanisms for controlling the pandemic are quarantines, perimeter closures and social distancing with the aim of reducing mobility. Governments only apply these measures for a reduced period, since they involve the closure of economic activities such as tourism, cultural activities, or nightlife. The main criterion for establishing these measures and planning socioeconomic subsidies is the evolution of infections. However, the collapse of the health system and the unpredictability of human behavior, among others, make it difficult to predict this evolution in the short to medium term. This article evaluates different models for the early prediction of the evolution of the COVID-19 pandemic to create a decision support system for policy-makers. We consider a wide branch of models including artificial neural networks such as LSTM and GRU and statistically based models such as autoregressive (AR) or ARIMA. Moreover, several consensus strategies to ensemble all models into one system are proposed to obtain better results in this uncertain environment. Finally, a multivariate model that includes mobility data provided by Google is proposed to better forecast trend changes in the 14-day CI. A real case study in Spain is evaluated, providing very accurate results for the prediction of 14-day CI in scenarios with and without trend changes, reaching 0.93 [Formula: see text], 4.16 RMSE and 1.08 MAE.

Teachers' interpersonal styles and fear of failure from the perspective of physical education students.

A growing body of research-based knowledge has been generated for the purpose of better understanding the reciprocal and dynamic relationship between teachers' instructional characteristics and students' psychosocial and learning outcomes. This study specifically examined the relationship between teachers' interpersonal styles and fear of failure outcomes in physical education students. Five hundred sixty-two middle school and high school students in Physical Education classes (PE) participated in the study. Students completed questionnaires that assessed instructors' autonomy-supportive and controlling teaching styles and students' own fear of failure. A person-centered analysis was used to test the hypotheses. The results revealed that higher teacher autonomy support was associated with lower student fear of failure. To the contrary, a controlling teaching style was associated with fear of failure in these students. Two profiles emerged in which moderate fear of failure was associated with a stronger perception of a controlling teacher style and lower levels of fear of failure were associated with greater perceived instructor support for autonomy.

[Dietary intake of trace elements and semen quality and reproductive hormone levels in young men: relationship with fertility]. / Oligoelementos en la dieta y calidad seminal y niveles de hormonas reproductivas en varones jóvenes: relación con la fertilidad.

OBJECTIVE: The aim of this study was to study the associations between dietary intake of trace elements and semen quality and reproductive hormones levels in young men. MATERIAL AND METHOD: This is a cross-sectional study in healthy male university students (n=209) recruited in Murcia Region (Spain) between 2010 and 2011. Dietary intake of trace elements (iron, iodine and cinc) was assessed using a validated food frequency questionnaire. Semen analysis (sperm concentration, motility and morphology) was carried out according to World Health Organization guidelines. Serum concentrations of follicle-stimulating and luteinizing hormones and testosterone were also determined. Kruskal-Wallis and Chi-squared tests were used in bivariate analysis and multiple lineal regression was used to adjust for significant covariates. RESULTS: A statistically significant inverse association between dietary intake of iron and sperm concentration (P, trend=0.01) and the percentage of progressive motile sperm (P, trend=0.004) were observed. No other significant associations for the remaining sperm parameters or reproductive hormones were detected. CONCLUSIONS: Our results show that high levels of iron may be associated with reduced sperm concentration and motility in young men. However, further studies are needed, particularly in other male populations consulting for infertility problems.

[Associations between dietary inflammatory index and male reproductive parameters]. / Asociaciones entre el índice inflamatorio de la dieta y parámetros reproductivos masculinos.

OBJECTIVE: The aim of this work was to assess the associations between the dietary inflammatory index (DII) and male reproductive parameters. MATERIAL AND METHOD: Cross-sectional study of 209 healthy male university students (18-23 years old) recruited from October 2010 to November 2011 in Murcia Region (Southern Spain). Semen analyses (sperm concentration, motility and morphology) were carried out according to World Health Organization guidelines. Serum concentrations of follicle-stimulating and luteinizing hormones, estradiol, inhibin b and testosterone were also determined. Diet intake was assessed using a validated food frequency questionnaire. The DII assessed the inflammatory potential of one's diet. Negative or positive values of DII reflected anti-inflammatory or pro-inflammatory dietary status, respectively. Linear regression was used to analyze the relation between the DII score and semen quality parameters and reproductive hormone levels adjusting for potential important covariates. RESULTS: We found statistically significant positive associations between the DII and progressive sperm motility (PR) (P, trend=0.03] and total sperm motility (PR+NP) (P, trend=0.04]. No significant associations were observed for other semen parameters or male reproductive hormones. CONCLUSIONS: Our results suggest that a pro-inflammatory dietary status may be associated with increased sperm motility in young men, but will not impact sperm count, morphology or reproductive hormones. However, further research is needed to confirm these findings and extend these results to other male populations.

Anogenital distance and variability in semen parameters.

The purpose of this study was to analyze whether the anogenital distance (AGD) was associated with variability in semen parameters. Semen parameters analyzed following the WHO guidelines and sperm DNA fragmentation were evaluated in 160 semen samples obtained over a period of a year from 16 healthy male volunteers. Two types of AGD measurements from the anus to the rear base of the scrotum (AGDAS) and to the cephalic insertion of the penis (AGDAP) were taken in each individual. The association between AGDs and semen parameters were studied using three statistical tools: a) general coefficient of variation (CV) and intra-individual coefficient of variation (CVi), b) general linear models for repeated measures, and c) mixed model fixed effects panel data. Men with shortened AGDAP have significantly greater intra-individual variability in sperm concentration, total sperm count, and normal sperm morphology. Conversely, greater total sperm motility was observed in men with long AGDAS. Shortened AGDAS was associated with less intra-individual variability of total sperm motility (progressive and non-progressive). AGD measurements were associated with the variability in semen parameters. AGD may be useful to determine intra-individual variability in semen parameters. ABBREVIATIONS: AGD: anogenital distance; AGDAP: anogenital distance from the anus to the cephalic insertion of the penis; AGDAS: anogenital distance from the anus to the rear base of the scrotum; AIC: Akaike information criteria; BMI: body mass index; CV: general coefficient of variation; CVi: intra-individual coefficient of variation; GLM: generalized linear model; PR+NP: total sperm motility.

[Relationship between anogenital distance and prognosis of prostate cancer.] / Relación entre distancia anogenital y pronóstico del cáncer de próstata.

OBJECTIVE: Anogenital distance (AGD), the distance from the centre of the anus to the genitals, is a sexually dimorphic phenotype in mammals. Several experimental studies have demonstrated that AGD is a biomarker of prenatal androgen exposure during the masculinisation period of development. The objective of this study was to assess the relationship between AGD (as an indirect marker of prenatal hormonal environment) and severity of the surgical specimen and prostate cancer (PCa) prognosis. METHODS: We conducted a cross-sectional study with a total of 119 PCa patients with confirmed biopsy of the tumour. Every participant underwent a physical examination where two variants of the AGD were assessed, a) from the anus to the cephalad insertion of the penis (AGDAP) and b) to the posterior base of the scrotum (AGDAS). To assess the association between both AGD and severity and PCa prognosis multiple logistic regression analysis was used. RESULTS: Longer AGDAS was significantly associated with biochemical recurrence and affected margins of the surgical specimen (OR: 2.5; IC 95%:1.2-5.5, and 2.8; IC 95%: 1.1-7.5, respectively). CONCLUSIONS: Our findings suggest that a higher prenatal androgen exposure, resulting in a longer AGD, is associated with worse prognosis of PCa.

Respuesta a diferentes escenarios y complicaciones hematológicas en COVID-19 / Response to different scenarios and hematological complications in COVID-19.

Las enfermedades infecciosas emergentes y reemergentes son desafíos constantes para la salud pública en todo el mundo. Los casos recientes de neumonía de causa desconocida en Wuhan, China, han llevado al descubrimiento de un nuevo tipo de Coronavirus (2019-nCoV), que son virus de Ácido Ribonucleico (RNA) envueltos, de forma común encontrados en humanos, otros mamíferos y aves, capaces de causar enfermedades respiratorias, entéricas, hepáticas y neurológicas 1. La amenaza a la salud de la infección por Coronavirus 2 asociado al SRAS (SARS-CoV-2) y la enfermedad que produce el mismo llamada Enfermedad por Coronavirus (COVID-19) ya está estable- cida con sus tasas de infección y mortalidad de manera considerable más altas si se lo compara con otros virus respiratorios adquiridos en la comunidad 2. En tal sentido es necesario dar una respuesta por parte de la Unidad Técnica de Hematología en relación a esta pandemia con el ánimo de aportar al manejo integral de estos pacientes, homogeneizar criterios clínicos, lidiar de mejor manera con la incertidumbre en el diagnóstico y tratamiento de COVID-19. El SARS CoV-2 y su enfermedad COVID-19, en la mayoría de pacientes tiene una presentación con síntomas leves. Sin embargo, en el 5% de los casos diagnosticados requerirán de una Unidad de Cuidados Intensivos (UCI)3, ya que presentan Síndrome de Dificultad Respiratoria Aguda (SDRA), shock séptico, Insuficiencia Multiorgánica y coagulopatía hemorrágica, así como trombótica, incluyendo Coagulación Intravascular Diseminada (CID), alcanzado en las salas de UCI una tasa mortalidad por COVID-19 entre el 22% al 62% en algunas series 4. Adicional, se ha observado que el grupo de pacientes con mala evolución presentan un estado hiperinflamatorio, asemejándose al cuadro clínico descrito de una linfohistiocitosis hemofagocítica secundaria, que en este caso sería desencadenada por SARS CoV-2 5. Un grupo de Hematólogos de diferentes hospitales de la ciudad de Quito: Especialidades Carlos Andrade Marín-Instituto Ecuatoriano de Seguridad Social (HECAM-IESS), Metropolitano; y, hospitales de la ciudad de Guayaquil: Teodoro Maldonado Carbo-IESS, Hospital Luis Vernaza y Clínica Gilbert, basados en la evidencia científica disponible y experticia profesional, elaboraron éste protocolo con las recomendaciones según los diferentes escenarios y complicaciones hematológicas.

Emerging and reemerging infectious diseases are constant challenges to public health worldwide. Recent cases of pneumonia of unknown cause in Wuhan, China have led to the discovery of a new type of Coronavirus (2019-nCoV), which are enveloped ribonucleic acid (RNA) viruses, commonly found in humans, other mammals, and birds, capable of cause respiratory, enteric, liver and neurological diseases 1. The health threat of SARS-associated coronavirus 2 (SARS-CoV-2) and the disease that produces it called COVID-19 has already been established with its considerably higher infection and mortality rates compared to other respiratory viruses acquired in the community 2. In this sense, it is necessary to give a response from the Hematology Technical Unit in relation to this pandemic in order to contribute to the comprehensive management of these patients, homogenize clinical criteria, better deal with uncertainty in the diagnosis and treatment of COVID-19. SARS CoV-2 and its disease COVID-19, in the majority of patients have a presentation with mild symptoms. However, in 5% of diagnosed cases they will require an Intensive Care Unit (ICU) 3, since they present Acute Respiratory Distress Syndrome (ARDS), septic shock, Multiple Organ Failure and hemorrhagic coagulopathy, as well as thrombotic, including Coagulation Disseminated Intravascular (DIC), achieved in the ICU wards a mortality rate for COVID-19 between 22% and 62% in some series 4. Additionally, it has been observed that the group of patients with poor evolution present a hyperinflammatory state, resembling the clinical picture of secondary hemopha- gocytic lymphohistiocytosis, which in this case would be triggered by SARS CoV-2 5. The group of Hematologists from the hospitals of the city of Quito: Specialties Carlos Andrade Marín HECAM-IESS, Metropolitano; and, hospitals in the city of Guayaquil: Teodoro Maldonado Carbo-IESS, Luis Vernaza Hospital and Gilbert Clinic, based on the available scientific evidence and professional expertise, prepared this protocol with the recommendations according to the different hematological scenarios and complications.

Obtención e infusión de plasma convaleciente de paciente recuperado de infección COVID-19 para uso compasivo / Obtaining and infusing convalescent plasma from a patient recovered from COVID-19 infection for compassionate use

El 30 de enero de 2020, la Organización Mundial de la Salud (OMS) declara que el brote de Enfermedad por Coronavirus (COVID-19) constituye una Emergencia Sanitaria de Salud de Preocupación Internacional/Public Health Emergencies of International Concern (PHEIC). El 11 de marzo de 2020, la OMS declara la pandemia1,2. El COVID-19 es una enfermedad respiratoria aguda causada por un coronavirus zoonótico de reciente aparición1. Los coronavirus son una familia de virus que se descubrió en la década de los 60 pero cuyo origen es todavía desconocido. Pueden causar enfermedades tanto en animales como en humanos. En los humanos se sabe que varios coronavirus (229E, OC43, NL63 y HUK 1) son responsables del resfriado común y en raras ocasiones se pueden producir infecciones graves de las vías respiratorias inferiores. Dos de los coronavirus causan infecciones en los seres humanos muchos más graves e incluso a veces mortales; estos son: el Coronavirus del Síndrome Respiratorio de Oriente Medio (MERS-CoV), y el Coronavirus tipo 2 asociado al SARS (SARS-CoV), que produce el síndrome respiratorio agudo grave3,4. La pandemia debida al virus SARS-CoV-2 requiere de medidas sanitarias urgentes encaminadas a reducir el riesgo de transmisión de la infección3,4. Al momento, no existe tratamiento eficaz para abordar la enfermedad por SARS-CoV-2 (COVID-19). La OMS emitió un informe que los primeros resultados con el uso de Plasma de Convaleciente (CP) puede ser una modalidad de tratamiento potencialmente útil para el COVID-193-5.En este sentido, se señaló la oportunidad de que los Sistemas Transfusionales de cada país realicen una evaluación de riesgos para calibrar su capacidad de extraer, preparar y almacenar este tipo de donaciones. Esto incluye recursos humanos y suministros críticos adecuados, así como un control exhaustivo de procedimientos e infraestructuras. En este marco, se sugiere el inicio de contactos con los servicios hospitalarios para que colaboren en la selección de pacientes, que habiendo superado la enfermedad del COVID-19, pudieran ser candidatos para donación de plasma sin mermar en sus derechos1. La decisión de desarrollar esta opción requiere una revisión rápida, pero exhaustiva, del agente etiológico o agentes relacionados y la respuesta inmune a ellos para evaluar los posibles beneficios y riesgos de la inmunización pasiva. Los principios generales establecidos en los documentos de posición de la Red de Reguladores de Sangre (BRN) de la OMS sobre el uso de plasma convaleciente, como elemento de respuesta a brotes anteriores de virus emergentes (2017) y como respuesta al Coronavirus del Síndrome Respiratorio de Oriente Medio (2014) siguen siendo aplicables también a esta pandemia de SARS-CoV-26,7. La falta de evidencia clínica concluyente del uso del plasma convaleciente en infección por SARS-CoV-2 no debería ser razón para abandonar el uso del plasma convaleciente. Los ensayos clínicos aleatorios están en curso y los resultados no estarán disponibles durante meses en tanto no hay justificación basada en la evidencia disponible y la ética profesional para negar categóricamente el uso del plasma convaleciente en los hospitales que no participan en un ensayo clínico aleatorio. El siguiente protocolo ha tomado algunas de las recomendaciones del Comité Científico para la Seguridad Transfusional del Ministerio de Sanidad de España Versión 1.0 ­ 26 marzo de 20201. Y ha sido modificado para tratar de adaptarlo a la realidad de nuestra institución.

On January 30, 2020, the World Health Organization (WHO) declared that the COVID-19 outbreak constitutes a public health emergency of international concern (PHEIC). On March 11, 2020, the WHO declared the pandemic1,2. COVID-19 is an acute respiratory disease caused by a newly emerging zoonotic coronavirus1. Coronaviruses are a family of viruses that was discovered in the 1960s but whose origin is still unknown. They can cause disease in both animals and humans. In humans, several coronaviruses (229E, OC43, NL63, and HUK 1) are known to be responsible for the common cold, and serious infections of the lower respiratory tract can rarely occur. Two of the coronaviruses cause much more serious and even sometimes fatal infections in humans; These are: MERS-CoV, as the cause of respiratory syndrome in the Middle East, and SARS-CoV, which produces severe acute respiratory syndrome3,4. The pandemic due to the SARS-CoV-2 virus requires urgent sanitary measures aimed at reducing the risk of transmission of the infection3,4. Currently, there is no effective treatment to address SARS-CoV-2 disease (COVID-19). The WHO issued a report that early results with the use of convalescent plasma (PC) may be a potentially useful treatment modality for COVID-193-5. In this sense, the opportunity for the Transfusion Systems of each country to carry out a risk assessment to gauge their ability to extract, prepare and store this type of donation. This includes adequate critical human resources and supplies, as well as a comprehensive control of procedures and infrastructure. In this framework, it is suggested that contacts with hospital services be initiated so that they collaborate in the selection of patients who, having overcome the COVID-19 disease, may be candidates for plasma donation without diminishing their rights1. The decision to develop this option requires a rapid, but comprehensive, review of the etiologic agent or related agents and the immune response to them to assess the possible benefits and risks of passive immunization. The general principles established in the position papers of the WHO Blood Regulators Network (BRN) on the use of convalescent plasma, as an element of response to previous outbreaks of emerging viruses (2017) and as a response to the syndrome coronavirus respiratory problems of the Middle East (2014) are still applicable to this SARS-CoV-2 pandemic6,7. The lack of conclusive clinical evidence of the use of convalescent plasma in SARS-CoV-2 infection should not be a reason to abandon the use of convalescent plasma. Randomized clinical trials are ongoing and results will not be available for months as there is no justification based on available evidence and professional ethics to categorically deny the use of convalescent plasma in hospitals that do not participate in a randomized clinical trial. The following protocol has taken some of the recommendations of the Scientific Committee for Transfusion Safety of the Spanish Ministry of Health Version 1.0 - March 26, 20201. And it has been modified to try to adapt it to the reality of our institution.