Double versus single stimulation in young low prognosis patients followed by a fresh embryo transfer: a randomized controlled trial (DUOSTIM-fresh).

STUDY QUESTION: Does double stimulation, followed by a fresh embryo transfer (DUOSTIM fresh) give a higher number of good-quality blastocysts as compared with a single stimulation in young low prognosis patients? SUMMARY ANSWER: Compared to single stimulation, DUOSTIM fresh leads to a significantly higher number of good quality blastocysts, without hindering fresh embryo transfer outcomes. WHAT IS KNOWN ALREADY: DUOSTIM (ovarian stimulation both in the follicular and luteal phase of the same cycle) is an innovative strategy to retrieve a higher number of oocytes in a shorter time frame, thus it is particularly appealing for poor ovarian responders. Three current limitations of dual stimulation are: (i) it is unclear whether outcomes of the second (luteal) wave result from the second stimulation, or a carry-over effect from previous follicular stimulation; (ii) the desynchronization between endometrium and ovaries and, (iii) lack of robust evidence. No previous studies explored DUOSTIM starting from the luteal phase, and with a fresh embryo transfer (DUOSTIM fresh). STUDY DESIGN, SIZE, DURATION: This study is a randomized, controlled, single-center, superiority clinical trial comparing two different ovarian stimulation protocols: a double stimulation cycle versus a single stimulation cycle followed by fresh embryo transfer. The primary outcome was the number of good quality blastocysts obtained, while secondary outcomes included results from fresh embryo transfer (clinical pregnancy, miscarriage). A total of 120 women were enrolled in this study between October 2020 and October 2022, with a 1:1 allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Only young (<40 years old) low prognosis (anti-Müllerian hormone <1.2 ng/ml) patients were recruited in the Reproductive Medicine Department of Dexeus University Hospital. In the investigational group, DUOSTIM fresh, the first stimulation was initiated in the luteal phase (Day 18-21 cycle) followed by a second stimulation 5 days post first oocyte retrieval, initiated in the follicular phase and a fresh embryo transfer of the best blastocyst generated (first or second cycle). The control group performed a follicular phase single stimulation cycle with a fresh embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 107 patients were analyzed, 53 in the investigational (DUOSTIM fresh) and 54 in the control arm (single stimulation). DUOSTIM fresh resulted in a significantly higher number of good quality blastocysts as compared to single stimulation (difference of mean 0.81, 95% CI 0.12-1.49). The mean percentage of cycles with embryo transfer was comparable (62.3% and 51.9%, respectively for double versus single stimulation). No significant differences were found for clinical outcomes following fresh embryo transfer with an ongoing pregnancy rate of 24.5% for DUOSTIM fresh versus 22.2%, for conventional IVF. Of interest comparisons between different stimulation cycles (A: luteal-phase DUOSTIM fresh, B: follicular-phase DUOSTIM fresh, and C: single stimulation) did not demonstrate any significant difference in terms of ovarian response with the mean (SD) number of mature oocytes being (A: 3.3 (2.9), B: 3.4 (3.4), and C: 3.5 (2.9), respectively). LIMITATIONS, REASONS FOR CAUTION: Study sample size was calculated to detect differences on the mean number of good quality blastocysts. Therefore, results for secondary outcomes (embryo transfer rates and clinical pregnancy rates) should be interpreted with caution as exploratory findings that deserve future investigations. WIDER IMPLICATIONS OF THE FINDINGS: Although DUOSTIM fresh results in a higher number of blastocysts as compared with a single stimulation in young low prognosis patients, the decision of performing dual stim should be evaluated with caution, considering that whether this may improve embryo transfers rate and pregnancy outcomes is still unclear. Results on cumulative-live-birth-rate are warranted. STUDY FUNDING/COMPETING INTEREST(S): The study was an investigator-initiated study supported by an unrestricted grant by Organon. N.P.P. has received grants from Merck Serono, Organon, Ferring Pharmaceutical, Theramex, and Besins Healthcare. N.P.P. has received consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. N.P.P. has received honoraria for lectures from Merck Serono, Organon, Theramex, Roche Diagnostics, IBSA, Besins Healthcare, and Ferring. A.R. has received Research grants, honoraria for lectures from Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins International, IBSA, Guerbet. The other authors declare that there is no conflict of interest to disclose with respect to the content of this article. TRIAL REGISTRATIO NUMBER: NCT04446845. TRIAL REGISTRATION DATE: 25 June 2020. DATE OF FIRST PATIENT'S ENROLMENT: 30 October 2020.

[Relationship between frailty and functional status in lung transplant candidates]. / Relación entre la fragilidad y la capacidad funcional en los pacientes candidatos a trasplante de pulmón.

INTRODUCTION: Lung transplant (LT) is one of the therapeutic options for patients with terminal respiratory diseases. It is highly important to incorporate the functional status and frailty assessment into the selection process of candidates for LT. OBJECTIVES: Identify the prevalence of frailty in the LT waiting list. Study the relationship between frailty, functional status, Lung Allocation Score (LAS) and muscular dysfunction. METHODOLOGY: Descriptive transversal study of patients on the waiting list for LT. POPULATION: 74 patients with chronic respiratory diseases assessed by the lung transplant committee and accepted to be transplanted in a university hospital in Barcelona. The outcome variables were frailty status was evaluate for SPPB test, functional capacity was evaluate for the six-minute walking test (6MWT) and muscular dysfunction. The results were analyzed with the statistical package STATA 12. RESULTS: Sample of 48 men and 26 women, with a median age of 56.55 years (SD 10.87. The prevalence of frailty assessed with the SPPB was 33.8% (8.1% are in frailty and 25.7% are in a state of pre-frailty). There is a relationship between the SPPB, 6MWT and maximal inspiratory pressure, but not with others force values. There is a relationship between the risk of frailty (scores below 9 in SPPB) and the meters walked in 6 but not with the LAS. CONCLUSIONS: The risk of frailty in patients with terminal chronic respiratory diseases is high. Frailty is related with functional capacity, but not with LAS.

Late diagnosis of sitosterolemia in an adult case with unexplained hemolytic anemia.

Sitosterolemia is a rare autosomal recessive disease that lead to an increase in the intestinal absorption and decreased biliary excretion plant sterols. It is caused by mutations in ABCG5 and ABCG8 genes, encoring sterolin-1 and sterolin-2 protein. The main clinical manifestations are xanthomas, premature atherosclerosis, arthralgia and, of note, hematological alterations. As in many other systemic diseases, hematological manifestations may be the only notable finding, for this reason we want to highlight the importance of multidisciplinary work and raise awareness of this rare disease that can lead to serious consequences if not treated prematurely. Here we present a case of this disease as well as its entire diagnostic process developed from a simple analytical alteration.

Predicting concentrations of volatile and semi-volatile compounds in indoor areas through analysis of condensed water samples. A proof of concept.

Atmospheres from indoor areas contain a range of volatile and semi-volatile compounds to which inhabitants are exposed through breathing. Despite different qualitative approaches have been proposed for the identification of compounds associated to the vapor phase of confined areas, active sampling remains as the preferred technique when quantitative data is required. Herein, we investigate the correlations existing between concentrations in air and water condensates obtained from indoor areas. To this end, samples of both matrices were simultaneously collected and analyzed by gas chromatography mass spectrometry. After validation of sample concentration approaches for a selection of compounds, the effect of different operational conditions, and environmental variables, in their concentrations in condensed water was assessed. Levels in this matrix were hardly affected by sampling time, air flow through the dehumidifier device, and the environmental temperature and humidity. Thus, air water distribution coefficients (Kaw) could be estimated for fourteen out of sixteen pre-selected compounds. These values permitted a semiquantitative evaluation of their concentrations existing in air from different areas. In case of semi-volatile compounds (i.e. phenol, benzothiazole, phthalates), with log Kaw below -4.8, analysis of 50 mL water samples permitted to achieve lower limits of quantification than active air sampling for 3 h at a flowrate of 1 m3 h-1.

[Medial discoid meniscus in a pediatric patient. Case report and review of the literature]. / Menisco discoide medial en paciente pediátrico. Presentación de un caso y revisión de la literatura.

Discoid meniscus is a congenital morphological variant of the meniscus, which tends to occur more frequently in its lateral form than in the medial form. This anomaly is characterized by central hypertrophy of the meniscus and a larger diameter than the normal meniscus, resulting in an abnormal shape and greater coverage of the tibial plateau. The clinical presentation of this condition varies depending on the stability of the meniscus. In pediatric patients, in particular, it is common to experience progressive and atraumatic symptoms, such as pain and limited mobility. Diagnosis is based on imaging studies, with magnetic resonance imaging being the preferred tool, where the "bowtie sign" is a classic finding. Surgery is recommended for symptomatic patients, with a focus on preserving the peripheral portion of the meniscus. Saucerization is the most commonly used technique, followed by stability assessment to determine if additional procedures are required. In this case, a 9-year-old patient with a medial discoid meniscus presented symptoms following trauma. Despite this atypical presentation, a successful outcome was achieved through arthroscopic surgery, underscoring the importance of accurate diagnosis and proper management of this condition in pediatric patients. Understanding the anatomical and pathophysiological characteristics of the discoid meniscus is essential for an effective therapeutic approach.

El menisco discoide es una variante morfológica congénita del menisco, que suele presentarse con mayor frecuencia en su forma lateral que en la medial. Esta anomalía se caracteriza por la hipertrofia central del menisco y un diámetro mayor que el menisco normal, lo que resulta en una forma anormal y una mayor cobertura del platillo tibial. La presentación clínica de esta condición varía según la estabilidad del menisco. En pacientes pediátricos, en particular, es común experimentar síntomas progresivos y atraumáticos, como dolor y limitación de la movilidad. El diagnóstico se basa en estudios de imagen, siendo la resonancia magnética la herramienta preferida, donde el "signo del corbatín" es un hallazgo clásico. Se recomienda la cirugía para pacientes sintomáticos, con un enfoque en preservar la porción periférica del menisco. La saucerización es la técnica más utilizada, seguida de la evaluación de la estabilidad para determinar si se requiere un procedimiento adicional. En el presente caso, se describe a un paciente de nueve años con un menisco discoide medial que manifestó síntomas después de un traumatismo. A pesar de esta presentación atípica, se logró un resultado exitoso mediante una cirugía artroscópica, lo que resalta la importancia de un diagnóstico preciso y un manejo adecuado de esta condición en pacientes pediátricos. La comprensión de las características anatómicas y patofisiológicas del menisco discoide es esencial para un enfoque terapéutico efectivo.

[Translated article] Mechanical properties variations of immature bone in the earliest stages of development.

INTRODUCTION: Bone as a material varies its composition and mechanical properties throughout life. Although these variations are better understood in adulthood, there is little experimental information on the variation of these properties in early stages of development. The objective of this study is to analyze the mechanical behavior and chemical properties of cortical bone tissue from two animal species in these earliest stages. MATERIAL AND METHODOLOGY: Twenty specimens of cortical bone were manufactured from bovine and ovine species that were in different stages of development (feeding exclusively on breast milk, in the transition period to feed or pasture, and young animals but on a solid food diet). The specimens were subjected to tensile tests, recorded with a high-speed camera to obtain deformation maps. Measurements of the tensile force until the specimen broke were also carried out. A fractographic study was carried out with a scanning electron microscope to analyze the fracture surface and an analysis of the amount of calcium in each of the specimens using X-ray dispersion spectroscopy. RESULTS: A statistically significant and positive correlation was found between the elastic modulus of the specimens and their calcium content. A trend towards more rigid behavior with age was observed. CONCLUSIONS: Young bone tissue tends to stiffen with age as the calcium content increases with an increase in elastic modulus.

Identification of hazardous organic compounds in e-waste plastic using non-target and suspect screening approaches.

End-of-life electric and electronic devices stand as one of the fastest growing wastes in the world and, therefore, a rapidly escalating global concern. A relevant fraction of these wastes corresponds to polymeric materials containing a plethora of chemical additives. Some of those additives fall within the category of hazardous organic compounds (HOCs). Despite the significant advances in the capabilities of analytical methods, the comprehensive characterization of WEEE plastic remains as a challenge. This research strives to identify the primary additives within WEEE polymers by implementing a non-target and suspect screening approach. Gas chromatography coupled to time-of-flight mass spectrometry (GC-QTOF-MS), using electron ionization (EI), was applied for the detection and identification of more than 300 substances in this matrix. A preliminary comparison was carried out with nominal resolution EI-MS spectra contained in the NIST17 library. BPA, flame retardants, UV-filters, PAHs, and preservatives were among the compounds detected. Fifty-one out of 300 compounds were confirmed by comparison with authentic standards. The study establishes a comprehensive database containing m/z ratios and accurate mass spectra of characteristic compounds, encompassing HOCs. Semi-quantification of the predominant additives was conducted across 48 WEEE samples collected from handling and dismantling facilities in Galicia. ABS plastic demonstrated the highest median concentrations, ranging from 0.154 to 4456 µg g-1, being brominated flame retardants and UV filters, the families presenting the highest concentrations. Internet router devices revealed the highest concentrations, containing a myriad of HOCs, such as tetrabromobisphenol A (TBBPA), tribromophenol (TBrP), triphenylphosphate (TPhP), tinuvin P and bisphenol A (BPA), most of which are restricted in Europe.

Validation of ADNEX and IOTA two-step strategy and estimation of risk of complications during follow-up of adnexal masses in low-risk population.

OBJECTIVES: The aim is to evaluate the ability of the Assessment of Different NEoplasias in the adneXa model (ADNEX) and the International Ovarian Tumour Analysis (IOTA) two-step strategy to predict malignancy in adnexal masses detected in an outpatient low-risk setting, and to estimate the risk of complications in masses with benign ultrasound morphology managed with clinical and ultrasound follow-up. METHODS: This single center (Hospital Universitari Dexeus Barcelona) study was performed using interim data of the ongoing prospective observational IOTA phase 5 study. The primary aim of the IOTA 5 study is to describe the cumulative incidence of complications during follow-up of adnexal masses classified as benign on ultrasound. Consecutive patients with adnexal masses detected between June 2012 and September 2016 in a private center offering screening for gynecological cancers were included and followed-up until February 2020. Tumors were classified as benign or malignant based on histology (if patients underwent surgery) or outcome of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when follow-up information was uncertain. The ability of the ADNEX model without CA125 and of the IOTA two-step strategy to distinguish benign from malignant masses was evaluated retrospectively using the prospectively collected data. We describe performance as discrimination (area under the receiver operating characteristic curve, AUC), calibration, classification (sensitivity and specificity) and clinical utility (Net Benefit). In the group of patients with a benign looking mass selected for conservative management we evaluated the occurrence of spontaneous resolution or any mass complication during the first 5 years of follow-up by assessing the cumulative incidence for malignancy, torsion, cyst rupture, or minor mass complications (inflammation, infection, or adhesions) and the time to occurrence of an event. RESULTS: A total of 2654 patients were recruited to the study. After application of exclusion criteria, 2039 patients with a newly detected mass were included for the model validation. 1684 (82.6%) masses were benign, 49 (2.4%) masses were malignant and for 306 (15.0%) masses the outcome was uncertain and imputed. The AUC was 0.95 (95% CI 0.89-0.98) for ADNEX and 0.94 (95% CI 0.88-0.97) for the two-step strategy. Calibration performance could not be meaningfully interpreted due to few malignancies resulting in very wide confidence intervals. The two-step strategy had better clinical utility than ADNEX at malignancy risk thresholds < 3%. 1472 (72%) patients had a mass judged to be benign based on pattern recognition by an experienced ultrasound examiner and were managed with clinical and ultrasound follow-up. In this group, the 5-year cumulative incidence was 66% for spontaneous resolution of the mass (95% CI 63-69), 0% for torsion (95%CI 0-0.002), 0.1% for cyst rupture (<0.1-0.6), 0.2% for a borderline tumor (<0.1-0.6), and 0.2% (0.1-0.6) for invasive malignancy. CONCLUSIONS: The ADNEX model and IOTA two-step strategy performed well to distinguish benign from malignant adnexal masses detected in a low-risk population. Conservative management is safe for masses with benign ultrasound appearance in such a population. This article is protected by copyright. All rights reserved.

Variants rs2758346, rs5746094, and rs2758331 of SOD2 gene: association study with breast cancer in a Mexican population and their analysis in silico.

OBJECTIVE: The aim of the study was to analyze the association between the superoxide dismutase 2 (SOD2) gene variants rs2758346, rs5746094, and rs2758331 and breast cancer (BC) in the Mexican population as well as to perform in silico assessments of the variants' potential impact. PATIENTS AND METHODS: We performed in silico analysis and analyzed 489 healthy women and 467 BC patients using TaqMan assays and Real-Time PCR. RESULTS: The TT genotype, the T allele of the rs2758346 variant, and the CC genotype of both rs5746094 and rs2758331 were identified as BC risk factors (p < 0.05). The TT and CTTT genotype of the rs2758346 variant stratified by the presence of ki-67 (> 20%), TCCC, and estrogen receptor (ER)-positive of the rs5746094 variant, and the CC and CT genotypes of rs2758331 stratified by menopause status and non-chemotherapy response were risk factors. The TTC and TTA haplotypes are risk factors for BC. In silico analysis revealed that the rs2758346, rs5746094, and rs2758331 variants could influence SOD2 gene regulation by transcription factors and circulating RNAs (circRNAs). CONCLUSIONS: The rs2758346, rs5746094, and rs2758331 variants of the SOD2 gene were associated with BC risk and could influence SOD2 regulation by transcription factors and circRNAs.

Controversies in point-of-care 3D printing for oncological and reconstructive surgery with free software in oral and maxillofacial surgery: European regulations, costs, and timeframe.

The aim of this paper is to discuss the controversies surrounding the most recent European regulations, as well as the cost, for a 3D printing workflow using free-source software in the context of a tertiary level university hospital in the Spanish public health system. Computer-aided design and manufacturing (CAD/CAM) for head and neck oncological surgery with the printing of biomodels, cutting guides, and patient-specific implants has made it possible to simplify and make this type of highly complex surgery more predictable. This technology is not without drawbacks, such as increased costs and the lead times when planning with the biomedical industry. A review of the current European legislation and the literature on this subject was performed, and comparisons made with the authors' in-house 3D printing setup using free software and different 3D printers. The cost analysis revealed that for the cheapest setup with free software, it would be possible to amortize the investment from case 2, and in all cases the initial investment would be amortized before case 9. The timeframe ranged from 2 weeks with the biomedical industry to 72 h with point-of-care 3D printing. It is now possible to develop point-of-care 3D printing in any hospital with almost any budget.

Assessment of the occurrence and interaction between pesticides and plastic litter from vineyard plots.

In this research, aged plastic fragments collected from vineyards were characterized in terms of composition, residues of pesticides, and their potential to exchange these compounds with the aquatic media. To this end, we employed the qualitative and quantitative information provided by complementary analytical techniques, including chromatography, organic and inorganic mass spectrometry, infrared spectroscopy and electronic microscopy. Debris of weathered plastics were identified as polypropylene and polyethylene, containing different types of additives, from organic UV stabilizers to inorganic fillers, such as calcium salts. Regardless of polymer type, plastic litter collected from vineyards contained residues of pesticides, and particularly of fungicides, with total concentrations in the range of values from 114 ng g-1 to 76.4 µg g-1. Data obtained under different extraction conditions suggested that a fraction of these compounds was absorbed in aged polymers, penetrating inside the material. The parallel analysis of plastic litter and vineyard soils reflected higher pesticide residues in the former matrix. Furthermore, several fungicides, considered as labile in vineyard soils (i.e. zoxamide and folpet), were those showing the highest levels in plastic litter. Simulated sorption-desorption studies, with plastic debris in contact with surface water, demonstrated the higher affinity of aged materials by moderately polar pesticides than their new counterparts. For the first time, the manuscript highlights the presence of plastic litter in vineyards soils, reflecting the accumulation of several fungicides in this matrix, in some cases, with a different stability pattern to that observed in the soil from same vineyards.

Mechanical properties variations of immature bone in the earliest stages of development. / Variación de las propiedades mecánicas del hueso inmaduro en las etapas más tempranas del desarrollo.

INTRODUCTION: Bone as a material varies its composition and mechanical properties throughout life. Although these variations are better understood in adulthood, there is little experimental information on the variation of these properties in early stages of development. The objective of this study is to analyze the mechanical behavior and chemical properties of cortical bone tissue from two animal species in these earliest stages. MATERIAL AND METHODOLOGY: Twenty specimens of cortical bone were manufactured from bovine and ovine species that were in different stages of development (feeding exclusively on breast milk, in the transition period to feed or pasture, and young animals but on a solid food diet). The specimens were subjected to tensile tests, recorded with a high-speed camera to obtain deformation maps. Measurements of the tensile force until the specimen broke were also carried out. A fractographic study was carried out with a scanning electron microscope to analyze the fracture surface and an analysis of the amount of calcium in each of the specimens using X-ray dispersion spectroscopy. RESULTS: A statistically significant and positive correlation was found between the elastic modulus of the specimens and their calcium content. A trend towards more rigid behavior with age was observed. CONCLUSIONS: Young bone tissue tends to stiffen with age as the calcium content increases with an increase in elastic modulus.

Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe.

In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.