A deep interaction between the endometrium and the invading trophoblast occurs during implantation in humans, with the acquisition of uterine receptivity to the invading embryo promoted by an ...elevation of pro-inflammatory cytokines in the endometrium, and the invasiveness of decidualizing endometrial stromal cells, augmented by trophoblast-derived signals. Considering that usage of angiotensin II type 1 (AT1) receptor blockers, among other renin-angiotensin system (RAS) antagonists, is associated with adverse pregnancy outcomes, here we aim to analyse the involvement of AT1 receptor in the reciprocal dialogue occurring between endometrial stroma and trophoblast cells. In human endometrial stromal cells (T-HESC) pre-incubated with a decidualization cocktail, angiotensin (Ang) II increased protein expression of prolactin and FOXO1, markers of endometrial decidualization, while promoting nuclear translocation of FOXO1. In addition, Ang II treatment increased CXCL8, and matrix metalloprotease (MMP)-2 levels in T-HESC. Incubation with the AT1 receptor blocker losartan or with an NFAT signalling inhibitor, decreased Ang II-induced secretion of prolactin, CXCL8, and MMP-2 in T-HESC. In a wound healing assay, conditioned medium (CM) obtained from Ang II-treated T-HESC, but not CM from losartan-pre-incubated T-HESC, increased migration of HTR-8/SVneo trophoblasts, effect that was inhibited in the presence of a CXCL8-neutralizing antibody. An increased secretion of CXCL8 and MMP-2 was observed after treatment of T-HESC with CM obtained from HTR-8/SVneo cells, which was not observed in T-HESC pre-incubated with losartan or with the NFAT inhibitor. This study evidenced a reciprocal RAS-coded messaging between trophoblast and ESC which is affected by the AT1 receptor blocker losartan.
•Ang II increased Prolactin and FOXO1 in decidualized endometrial stromal cells (ESC).•CXCL8 chemokine from Ang II-stimulated ESC, enhanced trophoblast migration.•AT1R/NFAT inhibition in ESC decreased decidualization and trophoblast migration.•Hormone-conditioned trophoblasts induced inflammatory events in ESC via AT1R/NFAT.•ESC/trophoblast crosstalk may be regulated by RAS-coded signals.
Osteoarthritis (OA) is a degenerative joint disease that affects the soft tissues and bones of involved articulations as a result of deregulation between synthesis and extracellular matrix ...degradation in articular cartilage. The present study evaluated the effect of intra-articular injection of human amniotic membrane (AM) as a treatment in an OA animal model in the knee. Chemical OA was developed in the knees of New Zealand rabbits. Once OA was established, the right knees only were treated with an intra-articular injection of human AM, with the left knees considered as a negative control group. The evaluation was performed at 3 and 6 weeks post-treatment. At 3 weeks post-injection, the cartilage exhibited fibrillation, erosion, cracks and cell clusters in the negative control group, but not in the treated group (P=0.028). At 6 weeks post-injection, the left knees exhibited hypertrophy, cracks, cell clusters, decreased matrix staining and structure loss. However, the right knees exhibited cell clusters without evidence of disruption in cartilage integrity (P=0.015). These results suggested that the intra-articular injection of human AM delays histological changes of cartilage in OA.
Background and ImportanceThe presence of epithelial corneal ulcers due to various reasons significanttly impacts in plenty of patient‘s quality of life. Recently, the use of topical insulin has ...emerged as a potential alternative treatment, with promising preclinical results. However, clinical evidence remains limited.The presence of insulin and insulin-like growth factor receptors in corneal keratocytes and epithelial cells may explain these findings.Aim and ObjectivesThese study aims is to assess the effectiveness and safety of insulin 1 IU/mL eye drops for persistent corneal ulcers (PCU).Material and MethodsObservational retrospective study conducted in a tertiary hospital among patients receiving topical insulin 1 IU/mL treatment for PCU between January 2021 and July 2023. Data collected included patient demographics, PCU etiology, treatment duration, prior and concurrent hospital treatments, clinical response (assessed via anterior segment biomicroscopy) and adverse effects.Pharmacy Hospital prepared insulin eye drops at a concentration of 1 IU/mL, and were administrated 3 or 4 times daily.Results54 patients were treated with 1 IU/mL topical insulin for PCU, including 23 (43%) males, with a median age of 70 (58–79) years. The most common PCU etiologies were post-surgical in 11 (20.4%) patients, herpetic in 10 (18.5%), neurotrophic in 9 (16.7%), dry eye in 6 (11.1%) and infectious in 5 (9.3%) patients. 8 (14.8%) patients had diabetes.12 (22.2%) and 16 (29.6%) patients previously received autologous serum or cyclosporine eye drops, respectively; and 9 (16.7%) and 12 (22.2%) concurrently used autologous serum or cyclosporine eye drops, respectively.The median duration of treatment was 2,2 (1.4–5.6) months. 17 (31.5%) patients finished treatment due to PCU improvement, 6 (11.1%) due to PCU resolution, 18 (33.3) due to lack of efficacy, 1 (1.9%) due to intolerance and 7 (13.0%) continued in treatment at follow-up ending. Patients with improvement or resolution had a treatment duration of less than 5 months.Response (PCU improvement or resolution) were better in infectious (60.0%) and post-surgical (54.5%).Conclusion and RelevanceThe 1 IU/mL topical insulin eye drops formulation appears to be an effective, safe and rapid option for patients with PCU. However, treatments without effectiveness in the first 5 months do not seem to be effective. Further studies are needed to confirm these findings.References and/or AcknowledgementsConflict of InterestNo conflict of interest.
Background and ImportanceMigraine is a highly disabling chronic disease. Erenumab is a preventive treatment to reduce frequency, intensity and duration of migraine crises, to improve the quality of ...life, reducing the impact of the disease on the functionality of the patient.Aim and ObjectivesThe aim was to evaluate the quality of life perceived by the patient before starting treatment with erenumab and after 12 months.Material and MethodsProspective observational study which includes patients with chronic or episodic high-frequency migraine treated with erenumab (August 2020 to December 2022), who had completed 12 months of treatment.Demographic data (sex; age), clinical data (type of migraine; monthly migraine days and intensity at the beginning of treatment and 12 months after) were collected and EuroQol-Questionnaire was performed to assess quality of life at the beginning and 12 months after.With EQ-5D-5L-Questionnaire, patients evaluate his own health status. Crosswalk Index Value Calculator and SPSS-Statistics v28.0.1.1 were used for the health status calculation.ResultsWe analysed 32 patients with a median age of 52 years (IQR: 46.45–59.4) being 27 women. Twenty-eight of them were diagnosed with chronic migraine and four with high frequency episodic migraine. Two patients stopped treatment before 12 months due to lack of response (excluded from the analysis).Average reduction in monthly migraines was 10.75 days (7.07–14.42). Mean migraines intensity before treatment was 8.6 (7.97–9.3); and 5.28 (4.18–6.37) after. Number of patients who report not having problems related to mobility, personal care, daily activities, pain/discomfort and anxiety/depression has increased and/or maintained after 12 months of treatment compared to baseline: 18 vs 21; 23 vs 23; 9 vs 18; 3 vs 12; and 6 vs 11, respectively. Mean according to EQ-5D-questionnaire before erenumab was 0.5694 (-0.008–1) and 0.7198 (-0.096–1) after. Improvement of quality life was considered statistically significant (p<0.01). Mean value of EVA scale before treatment was 50% (10–95%) and 68.5% (15–100%) after. Improvement in quality of life is considered statistically significant (p=0.008).Conclusion and RelevanceIt is important to carry out studies that include greater sample, but in our experience treatment with erenumab has been a great improvement in quality life of patients with migraine, thus reducing the impact of their disease in their day to day.References and/or Acknowledgements1. Eur J Neurol. 2021 May;28(5):1716–1725.Conflict of InterestNo conflict of interest.
Triphenylmethane-based polyimides and copolyimides containing bulky
t
-butyl group (
t
Bu) were obtained by one-step high temperature polycondensation of 2,2′-bis-(3,4-dicarboxyphenyl) ...hexafluoropropane dianhydride with diamines of triphenylmethane (TPM) family. The polymers were obtained in quantitative yields with inherent viscosities of 0.45–0.80 dL/g. They exhibited high thermal stability with 5% weight loss above 500 °C and were cast in films with good mechanical properties capable of testing as gas separation membranes. All polyimides were readily soluble in polar aprotic solvents, and the solubility enhanced with the increase in
t
Bu-group content. The amorphous, free-standing membranes were prepared from these polymers, and their permeabilities and selectivities to several gases were measured and discussed with respect to the structural differences in the polymers. It was shown that the presence of bulky
t
Bu-units made the chain packing less efficient; free volume and d-spacing in the polyimides grew accordingly. As a consequence, the membranes with higher content of
t
Bu-groups demonstrated improved permeabilities, showing 1.5–3.0 times higher permeability coefficients depending on the gas tested. The membranes’ separation performance was improved for CO
2
/CH
4
gas pair in comparison with that of structurally similar polyimides, while it did not change for O
2
/N
2
pair. Additionally, the mechanism of formation of triphenylmethane diamines in the reaction between aniline and benzaldehydes was investigated in order to optimize the monomer synthesis and to minimize possible side reactions. It was established that the secondary diamines, so-called aminals, were inevitable side products, particularly important in the condensation between aniline and
t
Bu-benzaldehyde.
The samples used were metallic surfaces and solid samples containing HEMs. Keywords: Highly energetic materials detection, infrared spectroscopy, Raman spectroscopy, HQI, PLS-DA discriminant ...analysis. 1. Los resultados muestran que podemos determinar si una muestra tiene material altamente energético utilizando los algoritmos HQI (Hit Quality Index) y Análisis discriminante por mínimos cuadrados parciales (PLS-DA). A continuación, la luz se devuelve por reflexión a la superficie de la muestra, produciendo un punto ligeramente mayor en la misma posición.
Background and importanceThe need to improve the quality of the unit-dose dispensing system was detected due to an increase in errors.Aim and objectivesQuantitative and qualitative analysis of errors ...in the dispensing of unit-dose drugs to implement measures to reduce them.Material and methodsProspective study, 2 months duration, in a tertiary hospital. The drug trolleys of two randomised nursing units were chosen from 16 hospitalisation units (589 beds) where unit-dose dispensing was reviewed daily. The review was conducted by a pharmacist and a pharmacy technician, using a protocol for quality control of the unit-dose dispensing system, which is based on the comparison of medication listings per patient with the drug content of the drug trolleys. Finally, the pharmacist makes a quantitative analysis: number and error rate (number of dispensing errors for every 100 changes); and qualitative analysis: type of error. The data obtained are analysed monthly.Results247 dispensing errors were detected, with a mean of 2823 (±124) revised changes per day. The median error rate was 1.23 (IR 0.48–1.99), the first month being 1.61 (IR 1.13–3.07), and 0.45 (IR 0–0.91) in the second month. The median error rate in the manually filled plants was 1.56 (IR 0.67–2.21) versus 0.92 (IR 0.57–1.24) in trolleys dispensed by automated dispensing cabinets. Filling the drug trolleys with an incorrect number of units was the most repeated error (44.13%, n=109), followed by the omission of introducing a medication (17.81%, n=44) and introducing a medication not prescribed (13.77%, n=34).Conclusion and relevanceFrom the error analysis we can conclude that:A reduction in potential dispensing errors was achieved, as the error rate decreased from 1.94 to 0.59 from the first to the second month.Increasing automated dispensing cabinets could help reduce errors, as plants filled without the help of electronic systems have a higher error rate (1.34 vs 1.16).There is a need to educate the pharmacy technicians about the impact of their work on the safety of hospitalised patient care, insisting on the need to check the number and name of the drugs introduced.References and/or acknowledgementsConflict of interestNo conflict of interest
Background and importanceUnresectable locally advanced non-small cell lung cancer (LA-NSCLC) long-term survival is poor. Durvalumab is approved as consolidation treatment in unresectable LA-NSCLC, ...without progression after chemoradiotherapy including platinum, with PD-L1 ≥1%.Aim and objectivesTo analyse the effectiveness and safety of durvalumab in the treatment of unresectable LA-NSCLC compared with the results of the pivotal study (PACIFIC). Secondary objective was influence of PD-L1 expression on effectiveness.Material and methodsRetrospective observational study of patients with unresectable LA-NSCLC treated with durvalumab in a tertiary hospital (August 2018–October 2021).Variables studied (electronic medical history): sex, age, Eastern Cooperative Oncology Group (ECOG), smoking, PD-L1, histology, disease stage. Variable to evaluate effectiveness: progression-free survival (PFS) from the start of treatment. For safety: adverse events (AE) and toxicity grade according to the Common Terminology Criteria for Adverse Events v5.0. Statistical analysis performed with SPSS v.23 software.ResultsThirty-one patients were included, mean age 66.45 (±9.45) years, male (74.2%), smokers (64.5%), ex-smokers (35.5%), World Health Organization (WHO) performance status: ECOG 0 (74.2%), ECOG 1 (25.8%). Disease stage IIIA (25.8%), IIIB (48.4%), IIIC (25.8%), squamous histology (41.9%), adenocarcinoma (41.9%) and unspecified (16.1%).41.9% received induction chemotherapy. Most common chemotherapy was cisplatin-vinorelbine (48.4%). Durvalumab was initiated a median of 55 (35–70) days after chemoradiotherapy. After initiating durvalumab, the median follow-up was 15 (5–22) months. Received a median of 13 (8–26) cycles. 35.5% (n=11) of patients completed 12 months of treatment, 29% (n=9) remain on treatment. Treatment discontinuation was 22.6% (n=7) due to disease progression and 12.9% (n = 4) due to severe toxicity. 51.6% (n = 16) presented toxicity associated with durvalumab: 68% (n=11) grade 1–2 toxicity. Main AEs: thyroid (19.32%) and cutaneous (22.54%) alterations.Median PFS was 14 (95% CI 7.59 to 20.4) months, with a PFS rate at 12 months (PFS12m): 70.6%. PFS12m was: 25% in PD-L1 <1% (n=4); 50% in PD-L1 1%–49% (n=10) and 73.33% in PD-L1 ≥50% (n=15).Conclusion and relevanceOur results showed, compared with the PACIFIC study, a lower median PFS (14 vs 17 months) and a higher PFS12m (70.6% vs 55.7%), results that seem comparable. In terms of safety, the results are similar to those of the PACIFIC study, so there is a good safety profile in our patients. The data analysed showed a lower effectiveness in PD-L1 <1%. However, a larger sample and follow-up are required to obtain conclusive results.References and/or acknowledgementsConflict of interestNo conflict of interest
In many countries, gastric cancer is not diagnosed until an advanced stage. An Internet-based e-learning system to improve the ability of endoscopists to diagnose gastric cancer at an early stage was ...developed and was evaluated for its effectiveness.
The study was designed as a randomized controlled trial. After receiving a pre-test, participants were randomly allocated to either an e-learning or non-e-learning group. Only those in the e-learning group gained access to the e-learning system. Two months after the pre-test, both groups received a post-test. The primary endpoint was the difference between the two groups regarding the rate of improvement of their test results.
515 endoscopists from 35 countries were assessed for eligibility, and 332 were enrolled in the study, with 166 allocated to each group. Of these, 151 participants in the e-learning group and 144 in the non-e-learning group were included in the analysis. The mean improvement rate (standard deviation) in the e-learning and non-e-learning groups was 1·24 (0·26) and 1·00 (0·16), respectively (P<0·001).
This global study clearly demonstrated the efficacy of an e-learning system to expand knowledge and provide invaluable experience regarding the endoscopic detection of early gastric cancer (R000012039).
•This report establishes that an e-learning system on the Internet can improve the diagnostic ability of endoscopists.•Countless endoscopists worldwide can access the system to learn how to make an endoscopic diagnosis of early gastric cancer.•The e-learning system could be modified to provide education regarding endoscopic diagnosis in other organs.
This is the first report to demonstrate how an e-learning system based on the Internet can improve the diagnostic ability of gastrointestinal endoscopists worldwide. There is no limit to the number of endoscopists who can access the system and benefit from this opportunity to learn how to make an endoscopic diagnosis of early gastric cancer. This e-learning system could be modified to provide education regarding endoscopic diagnosis in other organs such as the large intestine and the esophagus, as well as the stomach. It may contribute to human welfare and health by reducing the mortality from gastrointestinal cancer.
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