Site-specific sulfations regulate the physicochemical properties of papillomavirus-heparan sulfate interactions for entry.

Certain human papillomaviruses (HPVs) are etiological agents for several anogenital and oropharyngeal cancers. During initial infection, HPV16, the most prevalent cancer-causing type, specifically interacts with heparan sulfates (HSs), not only enabling initial cell attachment but also triggering a crucial conformational change in viral capsids termed structural activation. It is unknown, whether these HPV16-HS interactions depend on HS sulfation patterns. Thus, we probed potential roles of HS sulfations using cell-based functional and physicochemical assays, including single-molecule force spectroscopy. Our results demonstrate that N-sulfation of HS is crucial for virus binding and structural activation by providing high-affinity sites, and that additional 6O-sulfation is required to mechanically stabilize the interaction, whereas 2O-sulfation and 3O-sulfation are mostly dispensable. Together, our findings identify the contribution of HS sulfation patterns to HPV16 binding and structural activation and reveal how distinct sulfation groups of HS synergize to facilitate HPV16 entry, which, in turn, likely influences the tropism of HPVs.

Validation in Spanish and English of the Transgender Inclusive Behavior Scale.

The Transgender Inclusive Behavior Scale (TIBS) seeks to measure transgender-inclusive behavior, specifically actions and language use that support transgender people. The TIBS was developed in the United States. This study aimed to develop a Spanish version of the TIBS and confirm the structure of the English version to explore the psychometric properties and evaluate the construct validity in new contexts. We examined predictors of transgender-inclusive behavior by conducting a comparative analysis between participants from Spain and the United Kingdom. The study involved 1,110 university students, with 545 participants hailing from Spain (375 women, 162 men, and 8 non-binary individuals) and 565 participants from the United Kingdom (368 women, 178 men, and 19 non-binary individuals). Exploratory and confirmatory factor analysis were conducted to investigate and validate the factorial structure of the TIBS. The factor analysis results for the 15 items on the scale confirmed a three-dimensional structure in both languages. The scale score reliability was excellent with a Cronbach's alpha (α) = .95 in the British sample and with an α = .89 in the Spanish sample. Being a woman, being lesbian, gay, bisexual, trans, queer, intersex, and/or asexual, and being non-religious were the strongest predictors of inclusive behaviors towards transgender people in both countries. The correlations found indicated that people with lower sexual risk behaviors, and lower sexist, homophobic, and transphobic attitudes also presented higher inclusive behaviors towards trans people. These findings support the development of community strategies to increase the social inclusion of transgender people. The TIBS is a useful measure to track their success.

Bovine lactoferrin and chimera lactoferrin prevent and destroy Salmonella Typhimurium biofilms in Caco-2 cells.

Salmonellosis is a common foodborne disease caused by Salmonella bacteria. The emergence of multidrug-resistant (MDR) Salmonella serotypes, such as Typhimurium, and Salmonella's ability to form biofilms contribute to their resistance and persistence in host and non-host environments. New strategies are needed to treat or prevent Salmonella infections. This work aimed to determine the effect of the bovine lactoferrin (bLF) and lactoferrin chimera (LFchimera) in preventing or disrupting biofilms formed on abiotic surfaces or Caco-2 cells by Salmonella Typhimurium ATCC 14028 or an MDR strain. The inhibitory activity of planktonic bacteria, prevention of biofilm formation, and destruction of biofilms of S. Typhimurium (ATCC 14028 or MDR strain) on the abiotic surface and Caco-2 cells of bLF and LFchimera were quantified by CFU/ml and visualized by microscopy using Giemsa-stained samples. bLF (75-1000µM) and LFchimera (1-20µM) inhibited more than 95% of S. Typhimurium planktonic growth cultures (ATCC 14028 and MDR). In addition, bLF (600, 800, and 1000 µM) and LFchimera (10 and 20µM) prevented more than 98% of S. Typhimurium adherence and biofilm formation on Caco-2 cells. Finally, bLF (600 and 1000 µM) and LFchimera (10 and 20µM) destroyed more than 80% of S. Typhimurium biofilms established on abiotic and Caco-2 cells. In conclusion, bLF and LF chimeras have the potential to inhibit and destroy S. Typhimurium biofilms.

Analysis of the pH levels in energy and pre-workout beverages and frequency of consumption: a cross-sectional study.

BACKGROUND: Erosive tooth wear is an increasingly common pathology in the youth population. It refers to the chronic, localized, painless loss of dental hard tissues caused by non-bacterial acids, often originating from external sources like acidic beverages. Energy drink consumption is on the rise, frequently preceding physical exercise to enhance perceived energy levels. However, there are other types of beverages that also provide energy, such as pre-workout drinks, classified as sports drinks. The main objective of this research study has been conducted with the purpose of analyzing the pH of energy drinks and pre-workout beverages, and studying the frequency of consumption of such beverages in amateur athletes who practice sports. METHODS: A total of 67 beverages were examined, comprising 43 energy drinks and 24 sports supplementation beverages, also known as pre-workout or pre-training beverages. The participants were given a survey to complete. They were asked to respond whether they consumed any type of pre-workout or energy drink, and they were also asked about the timing of consumption. RESULTS: The findings indicated an average pH of 3.3 among the studied beverages, indicating a pH below the critical threshold. Out of the 113 participants, 51% reported taking some form of supplementation. CONCLUSIONS: Consequently, it was concluded that most of the analyzed beverages recorded pH values low enough to classify them as erosive, posing a threat to enamel surface. When analyzing the frequency of consumption of energy drinks and pre-workout beverages in amateur athletes, we observed that most participants aged 29 years or younger took supplements 3 to 5 times a week, while the older age groups more frequently took supplements 1 to 2 times a week.

A new drying method of thermolabile flexible endoscope channels by laminar and turbulent airflow - a prospective, randomized-controlled, single-center, proof-of-concept trial.

BACKGROUND AND AIMS: International guidelines suggest different possibilities for drying of endoscopes during reprocessing. Clinical results of these available drying methods are not satisfactory. The aim of this study was to compare the drying cycle of a standard endoscope washer-disinfector (EWD) (standard drying method [SD]) with a shortened mandatory drying by the EWD followed by a special drying device using laminar and turbulent air flow (novel drying method [ND]). PATIENTS AND METHODS: Sixty endoscopes (duodenoscopes, colonoscocopes and gastroscopes) from three different manufacturers underwent high-level disinfection and drying depending on the randomization group. Operational time of drying was measured for both groups. Residual fluid in the channels was measured using a laboratory scale. After a 14 day storage period, a sample of the endoscope channels was obtained to determine bacterial contamination. RESULTS: ND had significantly fewer residual water in endoscope channels (SD: 90% vs ND: 0%; p < 0.001) after high-level disinfection and drying, and less bacterial contamination after storage for 14 days (SD: 47% vs ND: 20%; p = 0.028). Time consumed for drying in ND was also significantly shorter (SD: 16min 4sec vs ND: 5min 59sec; p < 0.001). CONCLUSIONS: Drying with a special automatic drying device was superior compared with an EWD's drying program as evidenced by no measurable residual water, reduced microbiological contamination and a more than two-fold decrease in operational time. Thus, drying by laminar and turbulent airflow may represent an attractive alternative to the currently used standard approach in the reprocessing process of flexible endoscopes.

Characterization of unique B-cell populations in the circulation of people living with HIV prior to non-Hodgkin lymphoma diagnosis.

People living with HIV (PLWH) are at higher risk of developing lymphoma. In this study, we performed cytometry by time-of-flight (CyTOF) on peripheral blood mononuclear cells of cART-naïve HIV+ individuals and cART-naïve HIV+ individuals prior to AIDS-associated non-Hodgkin lymphoma (pre-NHL) diagnosis. Participants were enrolled in the Los Angeles site of the MACS/WIHS Combined Cohort Study (MWCCS). Uniform Manifold Approximation and Projection (UMAP) and unsupervised clustering analysis were performed to identify differences in the expression of B-cell activation markers and/or oncogenic markers associated with lymphomagenesis. CD10+CD27- B cells, CD20+CD27- B cells, and B-cell populations with aberrant features (CD20+CD27+CXCR4+CD71+ B cells and CD20+CXCR4+cMYC+ B cells) were significantly elevated in HIV+ cART-naïve compared to HIV-negative samples. CD20+CD27+CD24+CXCR4+CXCR5+ B cells, CD20+CD27+CD10+CD24+CXCR4+cMYC+ B cells, and a cluster of CD20+CXCR4hiCD27-CD24+CXCR5+CD40+CD4+AICDA+ B cells were significantly elevated in HIV+ pre-NHL (cART-naïve) compared to HIV+ cART-naïve samples. A potentially clonal cluster of CD20+CXCR4+CXCR5+cMYC+AICDA+ B cells and a cluster of germinal center B-cell-like cells (CD19-CD20+CXCR4+Bcl-6+PD-L1+cMYC+) were also found in the circulation of HIV+ pre-NHL (cART-naïve) samples. Moreover, significantly elevated clusters of CD19+CD24hiCD38hi cMYC+ AICDA+ B regulatory cells were identified in HIV+ pre-NHL (cART-naïve) compared to HIV+ cART-naïve samples. The present study identifies unique B-cell subsets in PLWH with potential pre-malignant features that may contribute to the development of pre-tumor B cells in PLWH and that may play a role in lymphomagenesis.

Celiac disease diagnosis: transglutaminase, duodenal biopsy and genetic tests correlations.

Introduction: Celiac disease (CD) is an autoimmune enteropathy triggered by gluten ingestion in genetically susceptible individuals. The haplotypes HLA-DQ2 and DQ8, transglutaminase (TGA) antibodies, and biopsy findings are the main tests performed in the evaluation and CD diagnosis. The objective was to establish possible correlations between transglutaminase levels, genetic markers tests, and qualitative intestinal biopsy findings (modified Marsh classification) at the diagnosis. Methods: A retrospective cohort study. The selection criteria were confirmed CD cases with genetic tests performed. Statistical analysis was done mainly through One-way ANOVA, Kendall's correlation coefficient (T), and linear regression. Results: The study included 112 patients, with a mean age of 6 ± 4 years. All cases were tested to HLA-DQ2, and it was positive in 93%. HLA-DQ8 was tested in 73% of cases and it was positive in 61%. The percentage of negative genetic markers (DQ2/DQ8) was 4.5% for patients tested to both haplotypes. A comparison of DQ2/DQ8 (positive and negative) with clinical findings and tests performed did not identify any differences for most of the parameters analyzed. Cases of type I diabetes presented significant negative expression for DQ2(-); p = 0.05 and positive expression for DQ8(+); p = 0.023. The TGA antibody levels ranged from 18 to 36,745 U/ml. An inverse correlation was found between age and TGA-L level (p = 0.043). In 23% of the cases, the TGA levels were greater than 1,000 U/ml and presented a moderate positive correlation with the atrophy biopsy profile (T = 0.245). Patients with an atrophic biopsy profile (Marsh III) had a moderate positive correlation with growth failure (T = 0.218) but a negative correlation with constipation (T = -0.277). Conclusion: In terms of diagnosis tests for CD, transglutaminase levels and age presented an inverse correlation, with the level decreasing as age increased. A moderately positive correlation was found between mean transglutaminase with intestinal atrophy and growth retardation. The genetic test DQ2 was positive for 93% and negative genetic markers (DQ2/DQ8) represented 4.5% of cases studied.

A CYCLIC PEPTIDE TARGETS GLIOBLASTOMA BY BINDING TO ABERRANTLY EXPOSED SNAP25.

Disease-specific changes in tumors and other diseased tissues are an important target of research because they provide clues on the pathophysiology of the disease as well as uncovering potentially useful markers for diagnosis and treatment. Here, we report a new cyclic peptide, CESPLLSEC (CES), that specifically accumulated (homed) in intracranial U87MG and the WT-GBM model of glioblastoma from intravenous (IV) injection, associating with the vasculature. Affinity chromatography of U87MG tumor extracts on insolubilized CES peptide identified Synaptosomal Associated Protein 25 (SNAP25) as a candidate target molecule (receptor) for CES. Several results supported the identification of SNAP25 as the CES receptor. IV-injected FAM-CES colocalized with SNAP25 in the tumors, and direct binding studies showed specific CES peptide binding to recombinant human SNAP25. A CES peptide-drug conjugate designed for photodynamic therapy showed selective cytotoxicity to SNAP25+ glioblastoma cell lines. Specific accumulation of systemically injected anti-SNAP25 antibody in U87MG glioblastoma, and labeling of intact U87MG cells with anti-SNAP in flow cytometry showed that SNAP25 is available from the circulation but not in normal tissues and that it is present at the cell surface. Using an array of ECM proteins and surface plasmon resonance revealed that SNAP25 binds moderately to collagen V and strongly to collagen VI. Modeling studies suggested that CES and collagen VI compete for the same binding site on SNAP25. Our results introduce CES as a valuable targeting peptide for drug delivery, and its receptor SNAP25 as a possible molecular marker of interest for glioblastoma.

A multicenter study of the risk of major bleeding in patients with and without cirrhosis undergoing percutaneous liver procedures.

Percutaneous liver procedures are frequently performed in patients with abnormal coagulation tests. Current guidelines suggest prophylactic transfusion is not mandatory in all patients with liver disease or cirrhosis, depending on the risk of bleeding. This study aims to describe the incidence and risk of major bleeding after percutaneous liver procedure in patients with and without cirrhosis. This retrospective study includes patients who underwent percutaneous liver biopsy and radiofrequency and microwave ablation of liver lesions at 3 centers in Spain. A transfusion protocol was considered for platelet counts <50,000 and/or international normalized ratio >1.5. The primary outcome was major bleeding. A total of 1797 patients were included in the study, with 316 having cirrhosis (18%) and 1481 without cirrhosis (82%). Among the patients with cirrhosis, 80 were classified as Child A, and percutaneous liver biopsy was the most frequent procedure (86%). Fourteen patients (0.8%) experienced major bleeding, with 0.4% occurring in radiofrequency and microwave ablation and 0.8% in percutaneous liver biopsy. Bleeding occurred in 0.6% of patients with cirrhosis compared to 0.8% in those without ( p = ns). No clinical or procedural variables were associated with bleeding. Twenty-five patients (1.4%) had an international normalized ratio >1.5, and 22 patients (1.2%) had a platelet count <50,000. Only 24% (6/25) of patients with an international normalized ratio >1.5 were transfused with fresh frozen plasma, and 72% (16/22) of those with platelet counts <50,000 received platelet transfusion. Patients with cirrhosis were more frequently transfused (5.9% vs. 1.5%). None of the patients who met the criteria for transfusion experienced major bleeding, regardless of whether they received a transfusion, and none of the patients who had a major bleeding episode met the transfusion criteria. In this cohort, major bleeding after percutaneous liver procedure occurred in <1% of patients, making it a low-risk procedure for patients with and without cirrhosis. Although not uniformly adopted, the current transfusion protocol still led to unnecessary blood product administration.

Disease and treatment burden of patients with haemophilia entering the explorer6 non-interventional study.

OBJECTIVES: We aimed to characterise baseline disease and treatment burden in a large population with haemophilia A/B, both with (HAwI/HBwI) and without (HA/HB) inhibitors. METHODS: The prospective, non-interventional explorer6 study included patients ≥12 years old with severe HA, severe/moderate HB or HAwI/HBwI of any severity, treated according to local standard of care (excluding previous/current exposure to concizumab or emicizumab). Baseline characteristics and historical clinical data were collected and patient-reported outcomes, including treatment burden, were assessed. RESULTS: The explorer6 study enrolled 231 patients with haemophilia (84 HAwI/HBwI) from 33 countries. At baseline, patients with HA/HB treated with prophylaxis had the lowest median annualised bleeding rates (ABRs; 2.0), irrespective of haemophilia type; of these patients, 27.5% (HA) and 31.4% (HB) had target joints. Patients with HAwI/HBwI treated episodically reported the highest treatment burden. Of these patients, 28.5% (HAwI) and 25.1% (HBwI) performed sports activities in the month before screening. CONCLUSION: Despite receiving routine clinical care, historical and baseline information from patients enrolled in explorer6 showed that patients with HA/HB treated episodically and patients with HAwI/HBwI had higher ABRs, higher treatment burden and participated in sports less than those with HA/HB treated with prophylaxis. Emerging treatments could be beneficial in addressing these unmet medical needs.

School Nursing Practice in Education Settings in Spain.

School nurses and pediatric nurses play vital roles in providing healthcare for children and adolescents in educational and healthcare settings. School nurses operate within educational institutions, serving as caregivers and facilitating communication between the school, families, and the healthcare system. These professionals closely collaborate with pediatric nurses. The primary objective of this study was to examine the state of school nursing in Spain. The research comprised 27 nurses, including 18 school nurses and 9 pediatric nurses, chosen through theoretical sampling. These nurses participated in in-depth interviews as part of the data collection process. Grounded theory, following Charmaz's process, was employed for data analysis. The findings underscore the nurses' call for their mandated presence and regulation in all Spanish educational institutions to address contemporary health challenges and ensure inclusive education.

The Hypoxic Burden, Clinical Implication of a New Biomarker in the Cardiovascular Management of Sleep Apnea Patients: A Systematic Review.

Background: Obstructive sleep apnea (OSA) is a highly prevalent sleep-disordered breathing. It is associated with adverse co-morbidities, being the most scientific evidence of cardiovascular (CV) disease. Currently, OSA is measured through the apnea-hypopnea index (AHI), the total number of respiratory events per hour of sleep. However, different studies have questioned its utility in OSA management, highlighting the need to search for new parameters that better reflect the heterogeneity of the disease. Hypoxic burden (HB) has emerged as a novel biomarker that informs about the frequency, duration and depth of the desaturation related to the respiratory events. We conducted a systematic review in order to find publications about the heterogeneity of OSA measured by HB and its associations with future disease. Methods: Systematic review was conducted using PubMed and Web of Science. The terms "sleep apne" and "hypoxic burden" were used to look for publications from the date of inception to August 15, 2023. Inclusion criteria: articles in English published in peer-reviewed journals. Exclusion criteria: (1) not available publications; (2) duplicated articles; (3) letters, editorials, and congress communications; (4) articles not including information about HB as a specific biomarker of OSA. Results: 33 studies were included. The results were classified in 2 main sections: (1) HB implication in the CV sphere: HB showed to be a better predictor of CV risk in OSA patients than traditional measures such as AHI with possible clinical management implication in OSA. (2) HB response to OSA treatment: pharmacological and nonpharmacological treatments have demonstrated to be effective in improving hypoxia measured through the HB. Conclusions: HB could be a better and more effective parameter than traditional measurements in terms of diagnosis, risk prediction and therapeutic decisions in patients with OSA. This measure could be incorporated in sleep units and could play a role in OSA management, driving the clinic to a more personalized medicine.

Exploring the Equilibrium State Diagram of Maltodextrins across Diverse Dextrose Equivalents.

This study investigates the equilibrium state diagram of maltodextrins with varying dextrose equivalents (DE 10 and 30) for quercetin microencapsulation. Using XRD, SEM, and optical microscopy, three transition regions were identified: amorphous (aw 0.07-0.437), semicrystalline (aw 0.437-0.739), and crystalline (aw > 0.739). In the amorphous region, microparticles exhibit a spherical morphology and a fluffy, pale-yellow appearance, with Tg values ranging from 44 to -7 °C. The semicrystalline region shows low-intensity diffraction peaks, merged spherical particles, and agglomerated, intense yellow appearance, with Tg values below 2 °C. The crystalline region is characterized by fully collapsed microstructures and a continuous, solid material with intense yellow color. Optimal storage conditions are within the amorphous region at 25 °C, aw 0.437, and a water content of 1.98 g H2O per g of dry powder. Strict moisture control is required at higher storage temperatures (up to 50 °C) to prevent microstructural changes. This research enhances understanding of maltodextrin behavior across diverse dextrose equivalents, aiding the development of stable microencapsulated products.

Diagnostic accuracy of serum calprotectin measured by CLIA and EIA in juvenile idiopathic arthritis: a proof-of-concept study.

Objective: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are used to assess disease activity in juvenile idiopathic arthritis (JIA). However, because these biomarkers do not always differentiate between active and inactive disease, there is a need for alternative markers such as serum calprotectin (sCal). The main aim of this proof-of-concept study was to assess the diagnostic accuracy of sCal in patients with JIA. Secondary aims were to identify the optimal sCal cut-off levels to define active disease and evaluate the association between these biomarkers and disease activity status. Methods: Serum samples were obtained from 25 pediatric patients with JIA. Serum calprotectin levels were determined by two different assays, the QUANTA FLASH chemiluminescence immunoassay (CLIA) from Inova Diagnostics and the solid-phase enzyme immunoassay (EIA) from Bühlmann Laboratories. Diagnostic accuracy was assessed for sCal CLIA, sCal EIA, CRP, and ESR. The results obtained by the CLIA and EIA methodologies were compared. We also evaluated the association between the individual each biomarkers (sCal CLIA, sCal EIA, CRP, and ESR) and disease activity (according to JADAS-27 criteria and the ACR criteria modified by Anink and colleagues). Results: For both sCal assays (CLIA and EIA), the optimal cut-off level (ROC analysis) was the same (2.3 µg/ml). Serum calprotectin levels measured by CLIA and EIA were strongly correlated with each other (Kendall's tau-b, 0.71; p < 0.001). Compared to ESR and CRP, sCal CLIA and EIA were both more accurate (i.e., greater sensitivity) in identifying patients with active disease. By contrast, ESR and CRP were more effective in identifying patients in remission (i.e., better specificity). Conclusion: This proof-of-concept study shows that determination of serum calprotectin levels with CLIA or EIA can accurately identify the presence of active disease in patients with JIA.

Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues.

Cellular senescence is a hallmark of advanced age and a major instigator of numerous inflammatory pathologies. While endothelial cell (EC) senescence is aligned with defective vascular functionality, its impact on fundamental inflammatory responses in vivo at single-cell level remain unclear. To directly investigate the role of EC senescence on dynamics of neutrophil-venular wall interactions, we applied high resolution confocal intravital microscopy to inflamed tissues of an EC-specific progeroid mouse model, characterized by profound indicators of EC senescence. Progerin-expressing ECs supported prolonged neutrophil adhesion and crawling in a cell autonomous manner that additionally mediated neutrophil-dependent microvascular leakage. Transcriptomic and immunofluorescence analysis of inflamed tissues identified elevated levels of EC CXCL1 on progerin-expressing ECs and functional blockade of CXCL1 suppressed the dysregulated neutrophil responses elicited by senescent ECs. Similarly, cultured progerin-expressing human ECs exhibited a senescent phenotype, were pro-inflammatory and prompted increased neutrophil attachment and activation. Collectively, our findings support the concept that senescent ECs drive excessive inflammation and provide new insights into the mode, dynamics, and mechanisms of this response at single-cell level.

Target engagement of an anti-MT1-MMP antibody for triple-negative breast cancer PET imaging and beta therapy.

PURPOSE: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks effective diagnostic and therapeutic options. Membrane type 1 matrix metalloproteinase (MT1-MMP) is an attractive biomarker for improving patient selection. This study aimed to develop a theranostic tool using a highly tumour-selective anti-MT1-MMP antibody (LEM2/15) radiolabelled with 89Zr for PET and 177Lu for therapy in a TNBC murine model. METHODS: The LEM2/15 antibody and IgG isotype control were radiolabelled with 89Zr. PET imaging was performed in a TNBC orthotopic mouse model at 1, 2, 4, and 7 days after administration. Tissue biodistribution and pharmacokinetic parameters were analysed and Patlak linearisation was used to calculate the influx rate of irreversible uptake. The TNBC mice were treated with [177Lu]Lu-DOTA-LEM2/15 (single- or 3-dose regimen) or saline. Efficacy of [177Lu]Lu-DOTA-LEM2/15 was evaluated as tumour growth and DNA damage (γH2AX) in MDA 231-BrM2-831 tumours. RESULTS: At 7 days post-injection, PET uptake in tumour xenografts revealed a 1.6-fold and 2.4-fold higher tumour-to-blood ratio for [89Zr]Zr-Df-LEM2/15 in the non-blocked group compared to the blocked and IgG isotype control groups, respectively. Specific uptake of LEM2/15 in TBNC tumours mediated by MT1-MMP-binding was demonstrated by the Patlak linearisation method, providing insights into the potential efficacy of LEM2/15-based treatments. A similar uptake was found for [89Zr]Zr-Df-LEM2/15 and [177Lu]Lu-DOTA-LEM2/15 in tumours 7 days post-injection (6.80 ± 1.31 vs. 5.61 ± 0.66 %ID/g). Tumour doubling time was longer in the [177Lu]Lu-DOTA-LEM2/15 3-dose regimen treated group compared to the control (50 vs. 17 days, respectively). The percentage of cells with γH2AX-foci was higher in tumours treated with [177Lu]Lu-DOTA-LEM2/15 3-dose regimen compared to tumours non-treated or treated with [177Lu]Lu-DOTA-LEM2/15 single-dose (12 % vs. 4-5 %). CONCLUSIONS: The results showed that the 89Zr/177Lu-labelled anti-MT1-MMP mAb (LEM2/15) pair facilitated immune-PET imaging and reduced tumour growth in a preclinical TNBC xenograft model.

Percutaneous Endoscopic Gastrostomy with T-Fasteners versus "Pull Technique": Analysis of Complications.

INTRODUCTION: The T-fasteners gastrostomy (T-PEG) has become increasingly popular over recent years as an alternative to the "pull-technique" gastrostomy (P-PEG). This study aimed to compare P-PEG and T-PEG complications. MATERIALS AND METHODS: A retrospective observational study of pediatric patients who underwent percutaneous endoscopic gastrostomy (PEG) placement. P-PEG was performed using the standard Ponsky technique and was replaced after 6 months by a balloon gastrostomy under sedation. T-PEG was performed using three percutaneous T-fasteners (that allow a primary insertion of a balloon gastrostomy). The balloon was replaced by a new one after 6 months without sedation. Complications were recorded. RESULTS: In total, 146 patients underwent PEG placement, 70 P-PEG and 76 T-PEG. The mean follow-up was 3.9 years (standard deviation = 9.6). Age, weight, and associated comorbidities were comparable (p > 0.05). The overall complications were 17 (24.2%) in the P-PEG group and 16 (21.0%) in the T-PEG group (p > 0.05). P-PEG was associated with more sedation for button replacement (97 vs. 2.6% [p < 0.05]). P-PEG was associated with more early tube dislodgement during the first replacement (7.2 vs. 1.4% [p = 0.092]). Two of the five dislodged gastrostomies in the P-PEG group underwent laparotomy due to peritonitis, whereas the only dislodged gastrostomy in the T-PEG group was solved endoscopically. Altogether, P-PEG was associated with more complications that required urgent endoscopy, laparotomy, or laparoscopy (18.6 vs. 6.6% [p < 0.05]). CONCLUSIONS: P-PEG was associated with more sedation, complications during first button replacement, and complications requiring urgent endoscopy, laparotomy, or laparoscopy compared with T-PEG.

Accuracy of the 6-Minute Walk Test for Assessing Functional Capacity in Patients With Heart Failure With Preserved Ejection Fraction and Other Chronic Cardiac Pathologies: Results of the ExIC-FEp Trial and a Meta-Analysis.

BACKGROUND: Heart diseases, particularly heart failure, significantly impact patient quality of life and mortality rates. Functional capacity assessment is vital for predicting prognosis and risk in these patients. While the cardiopulmonary exercise test is considered the gold standard, the 6-minute walk test has emerged as a more accessible alternative. However, the screening accuracy and optimal cut-off points of the 6-minute walk test for detecting severely reduced functional capacity in cardiac pathologies, including heart failure with preserved ejection fraction, are unclear. The study aimed to analyse the diagnostic accuracy of the 6-minute walk test for detecting reduced functional capacity, defined as VO2max < 14 ml/kg/min, compared with the cardiopulmonary exercise test in participants with heart failure with preserved ejection fraction using data from the "Ejercicio en Insuficiencia Cardiaca con Fracción de Eyección Preservada" (ExIC-FEp) trial; and to compare these results with previous studies investigating the screening accuracy for assessing functional capacity of the 6-minute walk test in participants with other chronic cardiac pathologies through a meta-analysis. RESULTS: The ExIC-FEp trial involved 22 participants with heart failure with preserved ejection fraction, who were not treated with beta-blockers, using the cardiopulmonary exercise test, specifically VO2max, as the reference test. The 6-minute walk test had a sensitivity of 70%, a specificity of 80%, and an area under the curve of 76% in the ExIC-FEp trial. Five studies were included in the meta-analysis showing a sensitivity of 79%, a specificity of 78%, and an area under the curve of 85%. CONCLUSION: In conclusion, the 6-minute walk test holds promise as a screening tool for assessing functional capacity in heart failure with preserved ejection fraction and chronic heart diseases, with a VO2max < 14 ml/kg/min as a reference point. It demonstrates moderate to good screening accuracy. However, the screening accuracy and optimal cut-off points of the 6-minute walk test for detecting severely reduced functional capacity, regardless of aetiology, are unclear. TRIAL REGISTRATION: NCT05726474. Registered 16 February 2023, https://clinicaltrials.gov/study/NCT05726474 .