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Placental growth factor at 24-28 weeks for aspirin discontinuation in pregnancies at high risk for preterm preeclampsia: Post hoc analysis of StopPRE trial
No full text20.500.12530/87845Introduction: This study aims to evaluate the safety of discontinuing aspirin treatment at 24-28 weeks in women at high risk after first-trimester combined screening for preeclampsia (PE) and normal placental growth factor (PlGF) levels at 24-28 weeks of gestation. Material and methods: This is a post hoc analysis of the StopPRE trial, conducted at nine Spanish maternity hospitals from September 2019 to September 2021. In the StopPRE trial, all high-risk single pregnancies identified during first-trimester screening for PE were treated with 150 mg of daily aspirin. Out of 1604 eligible women with a soluble fms-like tyrosine kinase-1 to PlGF ratio (sFlt-1/PlGF) = 100 pg/mL at 24-28 weeks were included. As in the StopPRE trial, the non-inferiority margin was set at a 1.9% difference in preterm PE incidence between the groups. Results: Among the 13 983 screened pregnant women, 1984 (14.2%) were deemed high-risk for preterm PE, of which 397 (20.0%) were ineligible, 636 declined participation, and 32 were excluded. Ultimately, 919 women with PlGF >100 pg/mL were randomized and included in this analysis. Preterm PE occurred in 0.9% of the intervention group (4 out of 465) and 1.5% of the control group (7 out of 454), indicating non-inferiority of aspirin discontinuation. There were no significant differences between the groups in adverse pregnancy outcomes before 37 weeks, at 100 pg/mL were randomized and included in this analysis. Preterm PE occurred in 0.9% of the intervention group (4 out of 465) and 1.5% of the control group (7 out of 454), indicating non-inferiority of aspirin discontinuation. There were no significant differences between the groups in adverse pregnancy outcomes before 37 weeks, at = 37 weeks. Minor antepartum hemorrhage incidence was significantly lower in the intervention group (absolute difference, -5.96; 95% CI, -10.10 to -1.82). Conclusions: Discontinuation of aspirin treatment at 24-28 weeks in women with PlGF levels >= 100 pg/mL was non-inferior to continuing until 36 weeks for preventing preterm PE. However, these findings should be interpreted with caution, as they originate from a subanalysis of the StopPRE trial
T-reg transcriptomic signatures identify response to check-point inhibitors.
No full textRegulatory T cells (Tregs) is a subtype of CD4+ T cells that produce an inhibitory action against effector cells. In the present work we interrogated genomic datasets to explore the transcriptomic profile of breast tumors with high expression of Tregs. Only 0.5% of the total transcriptome correlated with the presence of Tregs and only four transcripts, BIRC6, MAP3K2, USP4 and SMG1, were commonly shared among the different breast cancer subtypes. The combination of these genes predicted favorable outcome, and better prognosis in patients treated with checkpoint inhibitors. Twelve up-regulated genes coded for proteins expressed at the cell membrane that included functions related to neutrophil activation and regulation of macrophages. A positive association between MSR1 and CD80 with macrophages in basal-like tumors and between OLR1, ABCA1, ITGAV, CLEC5A and CD80 and macrophages in HER2 positive tumors was observed. Expression of some of the identified genes correlated with favorable outcome and response to checkpoint inhibitors: MSR1, CD80, OLR1, ABCA1, TMEM245, and ATP13A3 predicted outcome to anti PD(L)1 therapies, and MSR1, CD80, OLR1, ANO6, ABCA1, TMEM245, and ATP13A3 to anti CTLA4 therapies, including a subgroup of melanoma treated patients. In this article we provide evidence of genes strongly associated with the presence of Tregs that modulates the response to check point inhibitors
Synthetic suture tape for medial patellofemoral ligament reconstruction is an effective treatment for complex paediatric patellofemoral instability.
No full text20.500.12530/87897To assess the outcomes of medial patellofemoral ligament (MPFL) reconstruction using synthetic suture tape in paediatric patients with patellofemoral instability (PFI). This ambispective comparative study, conducted from 2014 to 2022, included paediatric patients who underwent MPFL reconstruction with synthetic suture tape and had a minimum follow-up of 1 year. Pre- and postoperative clinical and functional outcomes, patient satisfaction and complications were assessed. The study comprised 22 patients (29 knees), with a median age at surgery of 14.4 years (interquartile range [IQR] 10.9-16.7) and a median follow-up of 46.5 months (24.7-66). Notably, 13 knees (44.8%) had open growth plates at the time of surgery. The cohort included patients with Down syndrome (3 patients), Ehlers-Danlos (2), arthrogryposis (1), generalized joint hypermobility (8) and previous unsuccessful PFI surgeries (8). Concomitant procedures were performed on 16 knees. Postoperatively, improvements were observed in all but one patient, who reported residual pain. There were two other complications: one suture-tape rupture and one surgical wound infection. Functional scores significantly improved: Kujala, +14 points (7-29) (p MPFL reconstruction using synthetic suture tape is a viable and effective treatment for paediatric patients with PFI, particularly for those with connective tissue disorders, generalized joint hypermobility or past surgical failures, significantly enhancing clinical and functional outcomes with an acceptable complication rate. Level IV
Genetic association of the kynurenine pathway to suicidal behavior.
No full text20.500.12530/87854Suicidal behavior has been associated with dysfunctions in the kynurenine pathway, including alterations in the levels of neuroprotective and neurotoxic metabolites. Changes in the catalytic activity of enzymes within the pathway may contribute significantly. Variations in the genes encoding enzymes within the pathway can significantly affect their catalytic activity, playing a crucial role in the process. To explore this possibility, we hypothesized that these genetic variations would occur more frequently in patients with a history of suicidal behavior compared to non-suicidal individuals. Thus, we investigated the relationship between a history of suicide attempts and five single nucleotide polymorphisms (SNPs) within genes involved in the kynurenine pathway: IDO1 (rs7820268), IDO2 (rs10109853), KMO (rs1053230), KAT1 (rs10988134), and ACSMD (rs2121337). Our sample comprised 849 subjects: 325 individuals who had attempted suicide in their lifetime (SAs), 99 individuals with a history of major depression disorder but no previous suicide attempts (non-SAs), and 425 non-psychiatric controls (CTRL). We performed SNP association analyses using codominant, dominant, and recessive models. Adjustment for sex and multiple comparisons was applied. After adjustment, the analysis revealed that SAs showed a significantly higher frequency of T alleles and TT genotypes of the rs1053230 SNP compared to CTRL across nearly all models. Furthermore, in the recessive model, non-SAs displayed a higher prevalence of the TT genotype of the rs10109853 SNP compared to CTRL. The rs1053230 and rs10109853 SNPs could play a role in the previously observed metabolic dysregulation among SAs and non-SAs, respectively. To validate our findings, it is crucial to conduct functional analyses to investigate the impact of rs10109853 and rs1053230 SNPs on the expression and/or catalytic activity of the corresponding enzymes
Efectos de un yogur funcional enriquecido con fibra dietética soluble o proteína vegetal sobre el perfil del apetito. Ensayo clínico controlado, aleatorizado y de corta duración.
No full text20.500.12530/87913Introduction: designing functional foods to control appetite could be a useful strategy for managing overweight and obesity. Fiber and proteins could be interesting ingredients to consider. Objectives: to evaluate the appetite profile of two experimental yogurts (fiber-enriched [FEY] and protein-enriched [PEY]) versus a control yogurt (CY) in a group of overweight/obesity people. Material and methods: an acute, randomized, double-blind, crossover clinical trial was carried out in a group of twelve healthy overweight/obesity type I people; randomized to consume 3 yogurts in a different order for 3 acute study days. The appetite profile (1. hunger, 2. satiety, 3. fullness, 4. prospective food consumption, 5. desire to eat something fatty, salty, sweet or savoury) was assessed using a Visual Analog Scale (ranging from 0 ''not at all'' to 10 ''extremely") at 12 moments in each acute study. Additionally, total food consumption in an ad libitum lunch was assessed. Results: FEY produce a significantly lower desire to consume any food at 30 (1.50 ± 0.42) and 60 minutes (2.78 ± 0.42) after consumption compared to PEY (3.46 ± 0.53; 4.33 ± 0.54) and CY (3.27 ± 0.69; 4.0 ± 0.78) respectively (
Pre-existing cell populations with cytotoxic activity against SARS-CoV-2 in people with HIV and normal CD4/CD8 ratio previously unexposed to the virus.
No full textHIV-1 infection may produce a detrimental effect on the immune response. Early start of antiretroviral therapy (ART) is recommended to preserve the integrity of the immune system. In fact, people with HIV (PWH) and normal CD4/CD8 ratio appear not to be more susceptible to severe forms of COVID-19 than the general population and they usually present a good seroconversion rate in response to vaccination against SARS-CoV-2. However, few studies have fully characterized the development of cytotoxic immune populations in response to COVID-19 vaccination in these individuals. In this study, we recruited PWH with median time of HIV-1 infection of 6 years, median CD4/CD8 ratio of 1.0, good adherence to ART, persistently undetectable viral load, and negative serology against SARS-CoV-2, who then received the complete vaccination schedule against COVID-19. Blood samples were taken before vaccination against COVID-19 and one month after receiving the complete vaccination schedule. PWH produced high levels of IgG against SARS-CoV-2 in response to vaccination that were comparable to healthy donors, with a significantly higher neutralization capacity. Interestingly, the cytotoxic activity of PBMCs from PWH against SARS-CoV-2-infected cells was higher than healthy donors before receiving the vaccination schedule, pointing out the pre-existence of activated cell populations with likely unspecific antiviral activity. The characterization of these cytotoxic cell populations revealed high levels of Tgd cells with degranulation capacity against SARS-CoV-2-infected cells. In response to vaccination, the degranulation capacity of CD8+ T cells also increased in PWH but not in healthy donors. The full vaccination schedule against COVID-19 did not modify the ability to respond against HIV-1-infected cells in PWH and these individuals did not show more susceptibility to breakthrough infection with SARS-CoV-2 than healthy donors after 12 months of follow-up. These results revealed the development of protective cell populations with broad-spectrum antiviral activity in PWH with normal CD4/CD8 ratio and confirmed the importance of early ART and treatment adherence to avoid immune dysfunctions
Recent advances in combined Positron Emission Tomography and Magnetic Resonance Imaging
No full textHybrid imaging modalities combine two or more medical imaging techniques offering exciting new possibilities to image the structure, function and biochemistry of the human body in far greater detail than has previously been possible to improve patient diagnosis. In this context, simultaneous Positron Emission Tomography and Magnetic Resonance (PET/MR) imaging offers great complementary information, but it also poses challenges from the point of view of hardware and software compatibility. The PET signal may interfere with the MR magnetic field and vice -versa, posing several challenges and constrains in the PET instrumentation for PET/MR systems. Additionally, anatomical maps are needed to properly apply attenuation and scatter corrections to the resulting reconstructed PET images, as well motion estimates to minimize the effects of movement throughout the acquisition. In this review, we summarize the instrumentation implemented in modern PET scanners to overcome these limitations, describing the historical development of hybrid PET/MR scanners. We pay special attention to the methods used in PET to achieve attenuation, scatter and motion correction when it is combined with MR, and how both imaging modalities may be combined in PET image reconstruction algorithms
Preventing alpelisib-related hyperglycaemia in HR+/HER2-/PIK3CA-mutated advanced breast cancer using metformin (METALLICA): a multicentre, open-label, single-arm, phase 2 trial.
No full text20.500.12530/87908Hyperglycaemia is an early and frequent adverse event during alpelisib treatment. METALLICA aimed to evaluate prophylactic metformin to prevent or reduce hyperglycaemia occurrence in patients with HR+/HER2-/PIK3CA-mutated advanced breast cancer (ABC). Between August 13th, 2020 and March 23rd, 2022, this 2-cohort, phase 2, multicentre, single-arm trial (NCT04300790) enrolled patients with HR+/HER2-/PIK3CA-mutated ABC: cohort A, normal glycaemia (fasting plasma glucose 233 patients were screened, and 68 (20.2%) patients were enrolled in cohorts A (n = 48) and B (n = 20). Median follow-up was 7.8 months (IQR 1.4-19.6). Over the first 8 weeks, one (2.1%) of 48 patients in cohort A (95% CI: 0.5-11.1; P In HR+/HER2-/PIK3CA-mutated ABC, prophylactic metformin before alpelisib plus endocrine treatment has low incidence and severity of alpelicib-induced hyperglycaemia. Novartis Pharmaceuticals
Influence of Biometric and Corneal Tomographic Parameters on Normative Corneal Aberrations Measured by Root Mean Square
No full text20.500.12530/87909Background/Objectives: To determine the impact of corneal and biometry parameters on the normative root mean square (RMS) values of corneal aberrations measured at a 6 mm diameter. Methods: The RMS values for corneal aberrations (anterior, posterior, and total) were measured along with corneal parameters using Scheimpflug tomography on 770 normal subjects. The biometric parameters were measured with an optical biometer. A multiple linear regression model was used to assess the effect of these parameters on the RMS values for corneal aberrations. Results: The mean RMS values for low-order (LOAs) and high-order 6 mm aberrations (HOAs) were 1.883 +/- 0.797 mu m and 0.484 +/- 0.173 mu m, respectively, and for the anterior and posterior cornea, the values were 0.775 +/- 0.166 mu m and 0.189 +/- 0.036 mu m, respectively. For the anterior cornea, the main predictors of the RMS LOAs (R-2 = 69.8%) were anterior corneal astigmatism (ACA) and anterior corneal elevation (Ele F) on the apex (both
Schistosomiasis in migrant children and adolescents in a paediatric tropical referral unit in Spain: diagnosis and long-term management challenges.
No full text20.500.12530/87857Globalisation and population movement have led to an increasing number of migrant children residing in areas non-endemic for schistosomiasis. However, diagnosing and managing schistosomiasis in children remain controversial. This study aims to investigate the prevalence of schistosomiasis in migrant children and to describe the diagnostic approach and management strategies, including long-term follow-up, to explore the potential role of serological tests in evaluating treatment response. We conducted a retrospective descriptive study spanning from January 2014-July 2021 at a referral unit for Paediatric Tropical Diseases in Madrid (Spain). The study included patients under 18 years diagnosed with schistosomiasis. Of 679 children screened for schistosomiasis, 73 (10.8%) tested positive. The median age was 16.3 years [IQR 9-17.6], 74% male. The majority originated from Sub-Saharan Africa (47%) and Asia (47%). Only 40% presented with symptoms, with gastrointestinal (18%) and cutaneous (17%) manifestations being the most common. Eosinophilia was observed in 43% (median [IQR]: 1103/mm3 [671-1536]), and ova were visualised in the urine of 2/50 (4.0%). Praziquantel treatment was administered to 92%, and 5 patients required retreatment. Follow-up data were available for 58 (80%) over a median period of 9 months [IQR 6-19.8], revealing a progressive decline in eosinophil count, IgE titres, and ELISA optical density. Conclusion: In this series, the prevalence of schistosomiasis among migrant children was significant (10%), highlighting the importance of including serological tests in migrant health screening. The disease is largely asymptomatic, eosinophilia is often absent, and visualisation of ova in urine is exceedingly rare. Eosinophil count, IgE titres, and ELISA optical density could prove valuable as an initial approach for monitoring inflammation during follow-up assessments. What is Known: • The burden of disease related to schistosomiasis is significant, particulary in children, and it is advisable to screen this vulnerable population. What is New: • Eosinophilia may not be present in parasitic infections, so serological tests are crucial for screening migrant children. • Serological monitoring facilitates long-term management of migrant children with schistosomiasis