The impact of lutein-loaded poly(lactic-co-glycolic acid) nanoparticles following topical application: An in vitro and in vivo study.

Antioxidant therapies are of interest in the prevention and management of ocular disorders such as cataracts. Although an active area of interest, topical therapy with antioxidants for the treatment of cataracts is complicated by multiple ocular anatomical barriers, product stability, and solubility. Entrapment and delivery of antioxidants with poly(lactic-co-glycolic acid) nanoparticles is a possible solution to these challenges, however, little is known regarding their effects in vitro or in vivo. Our first aim was to investigate the impact of blank and lutein loaded PLGA nanoparticles on viability and development of reactive oxygen species in lens epithelial cells in vitro. Photo-oxidative stress was induced by ultraviolet light exposure with cell viability and reactive oxygen species monitored. Next, an in vivo, selenite model was utilized to induce cataract formation in rodents. Eyes were treated topically with both free lutein and lutein loaded nanoparticles (LNP) at varying concentrations. Eyes were monitored for the development of anterior segment changes and cataract formation. The ability of nanodelivered lutein to reach the anterior segment of the eye was evaluated by liquid chromatography coupled to mass spectrometry of aqueous humor samples and liquid chromatography coupled to tandem mass spectrometry (targeted LC-MS/MS) of lenses. LNP had a minimal impact on the viability of lens epithelial cells during the short exposure timeframe (24 h) and at concentrations < 0.2 µg LNP/µl. A significant reduction in the development of reactive oxygen species was also noted. Animals treated with LNPs at an equivalent lutein concentration of 1,278 µg /mL showed the greatest reduction in cataract scores. Lutein delivery to the anterior segment was confirmed through evaluation of aqueous humor and lens sample evaluation. Topical treatment was not associated with the development of secondary keratitis or anterior uveitis when applied once daily for one week. LNPs may be an effective in the treatment of cataracts.

Method for assessing coating uniformity of angioplasty balloons coated with poly(lactic-co-glycolic acid) nanoparticles loaded with quercetin.

In this study, we aim to quantify coating uniformity and correlate fluorescence intensity to drug loading for drug-coated angioplasty balloons (DCB) coated with 5, 10, 15, or 20 layers of poly(lactic-co-glycolic acid) nanoparticles (NPs) entrapped with quercetin. Uniformity was quantified from histograms and horizontal line profiles of microscopic fluorescent images acquired with sample specific parameters, and cracks in the coating were measured and counted. The fluorescence of images acquired with global parameters was correlated with quercetin loading measured via gravimetric/HPLC analysis. More layers on DCBs may be associated with less uniform coatings, as indicated by differences in histogram standard deviations. The line profile percent deviation from average for each sample was <20%. Cracks were present on all balloons, but their length was not significantly different between samples. The 5-layer DCBs had the fewest cracks, whereas the 15-layer DCBs had the most cracks. A strong positive correlation (R = 0.896) was identified between fluorescence intensity and drug loading. A relationship between the number of layers and coating uniformity seems to exist, but further investigations are required for confirmation. Fluorescence intensity appears to strongly predict drug loading, demonstrating that fluorescent imaging may be a viable alternative to drug release studies.

Ultrasound Changes in the Enthesis and Peri-enthesis Area of the Patellar and Achilles Tendons in Response to Physical Exercise: Comparison Between Healthy Subjects and Patients with Spondyloarthritis in Clinical Remission.

RATIONALE AND OBJECTIVES: The goal of achieving clinical remission in patients with spondyloarthritis does not necessarily include the resolution of entheseal inflammation from a histological perspective. However, enthesis not clinically inflamed, under mechanical stress, may behave differently from healthy subjects considering the physiopathology of SpA. Our goal was to determine whether ultrasound changes in entheses differ between SpA patients in clinical remission and healthy subjects. METHODS: SpA patients in clinical remission and matched healthy controls were recruited. At baseline, the following variables were measured on the dominant side by ultrasound: thickness of the distal patellar enthesis (hDP), the deep infrapatellar bursa (hDIB), the Achilles enthesis (hA), the preachilleal bursa (hPAB), effusion in the preachileal bursa (hePAB), and the presence of power Doppler signal in both enthesis. All measurements except hDP and hA were collected again after exercise (post-stress ultrasound). RESULTS: 30 patients and 30 controls were enrolled. In all subjects, hDIB, hPAB, and the preachileal bursa occupancy index increased significantly after the exercise. The increase was significantly greater in patients for all variables. At baseline, in patients, hyperemia was detected in one patellar tendon (3.3%) and in two Achilles tendons (6.7%). After exercise, the number of tendons with hyperemia increased to 11/30 (36.7%) and 12/30 (40%), respectively. Among controls, there was no detectable basal hyperemia, but after exercise, it was detected in 1/30 patellar tendons (3.3%) and 2/30 Achilles tendons (6.7%). CONCLUSION: Exercise triggers a greater effusive and hyperemic synovial response in patients in remission than in healthy controls. These findings suggest that the definition of remission should also include an assessment of the synovial response to mechanical stress.

Subclinical synovitis impact on the progression of lupus joint disease: A 10-year longitudinal multicenter study.

OBJECTIVE: To determine the effect of subclinical synovitis on the progression of joint disease in a cohort of patients with systemic lupus erythematosus over a mean follow-up of 10 years. METHODS: A longitudinal follow-up of 96 patients diagnosed with lupus was performed. All patients were considered clinically free of joint disease or with minimal joint impairment at baseline and were studied through ultrasound study of their dominant hand to assess the prevalence of subclinical synovitis. Now, over 10 years after we contacted them and reviewed their evolution to determine the impact of had or had not been diagnosed with subclinical synovitis in their current joint condition. RESULTS: Thirty-one of the 91 reached patients developed clinical progression in their joint manifestations (at least one ordinal degree of worsening). Of these, 23 (74,9%) had demonstrated subclinical synovitis at baseline. In the group of patients who did not progress clinically, 46 (76,6%) did not have this finding at the start of follow-up (p < .01, OR 9,44 95%CI 3,46-25,74). The patients in whom clinical progression was demonstrated had worse combined ultrasound scores than the rest of the patients: 6,41 SD 1,45 vs. 1,15 SD 0,97 (p < .01). CONCLUSIONS: The finding of subclinical synovitis in patients with systemic lupus erythematosus is associated with the development of joint disease progression both clinically and ultrasonographically.

Modulation of Methoxyfenozide Release from Lignin Nanoparticles Made of Lignin Grafted with PCL by ROP and Acylation Grafting Methods.

An efficient and sustainable agriculture calls for the development of novel agrochemical delivery systems able to release agrochemicals in a controlled manner. This study investigated the controlled release of the insecticide methoxyfenozide (MFZ) from lignin (LN) nanoparticles (LNPs). LN-grafted poly(ε-caprolactone) (LN-g-PCL) polymers were synthesized using two grafting methods, ring-opening polymerization (ROP)(LN-g-PCLp) and acylation reaction (LN-g-PCLa), creating polymers capable of self-assembling into nanoparticles of different properties, without surfactants. The LN-g-PCLp polymers exhibited a degree of polymerization (DP) from 22 to 101, demonstrating enhanced thermal stability after LN incorporation. LNPs loaded with MFZ exhibited a spherical core-shell structure with a hydrophilic LN outer layer and hydrophobic PCL core, with sizes affected by grafting methods and DP. LNPs controlled MFZ release, displaying variation in release profiles depending on the grafting methodology used, LN-g-PCLp DP, and temperature variations (23 to 30 °C). LNPs formulated with LN-g-PCLa showed a cumulative release of MFZ of 36.78 ± 1.23% over 196 h. Comparatively, increasing the DP of the LN-g-PCLp polymers, a reduction of the LNPs release rate from 92.39 ± 1.46% to 70.59 ± 2.40% was achieved within the same time frame. These findings contribute to identifying ways to modulate the controlled release of agrochemicals by incorporating them in renewable-based LNPs.

Validation and incorporation of digital entheses into a preliminary GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis.

OBJECTIVES: The main objective was to generate a GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis and to test its reliability. To this end, we assessed the validity, feasibility and applicability of ultrasound assessment of finger entheses to incorporate them into the scoring system. METHODS: The study consisted of a stepwise process. First, in cadaveric specimens, we identified enthesis sites of the fingers by ultrasound and gross anatomy, and then verified presence of entheseal tissue in histological samples. We then selected the entheses to be incorporated into a dactylitis scoring system through a Delphi consensus process among international experts. Next, we established and defined the ultrasound components of dactylitis and their scoring systems using Delphi methodology. Finally, we tested the interobserver and intraobserver reliability of the consensus- based scoring systemin patients with psoriatic dactylitis. RESULTS: 32 entheses were identified in cadaveric fingers. The presence of entheseal tissues was confirmed in all cadaveric samples. Of these, following the consensus process, 12 entheses were selected for inclusion in GLOUDAS. Ultrasound components of GLOUDAS agreed on through the Delphi process were synovitis, tenosynovitis, enthesitis, subcutaneous tissue inflammation and periextensor tendon inflammation. The scoring system for each component was also agreed on. Interobserver reliability was fair to good (κ 0.39-0.71) and intraobserver reliability good to excellent (κ 0.80-0.88) for dactylitis components. Interobserver and intraobserver agreement for the total B-mode and Doppler mode scores (sum of the scores of the individual abnormalities) were excellent (interobserver intraclass correlation coefficient (ICC) 0.98 for B-mode and 0.99 for Doppler mode; intraobserver ICC 0.98 for both modes). CONCLUSIONS: We have produced a consensus-driven ultrasound dactylitis scoring system that has shown acceptable interobserver reliability and excellent intraobserver reliability. Through anatomical knowledge, small entheses of the fingers were identified and histologically validated.

Usefulness of ultrasound in clinical decision-making in rheumatology clinical practice: A single-center longitudinal study.

OBJECTIVE: The purpose of the present study is to identify the extent to which it affects clinical decisions in a single-centre observational retrospective study. METHOD: The results of 801 requests and 1174 consecutive individual ultrasound examinations performed over 10 months were analysed. RESULTS: The most frequent indication was diagnostic assistance (39%) followed by assessment of inflammatory activity (34%). By topography, the hand was the most frequently studied region (51%), followed by the foot (18.1%). Of all requests, 67% had an impact on decision-making. The impact on clinical decision-making was associated with a shorter waiting time for the evaluation of the results, being the greatest in those ultrasound scans performed on demand on the same day of the request. In 73% of bilateral ultrasound studies, findings in one of the joints exemplified the overall result reported. CONCLUSIONS: Rheumatological musculoskeletal ultrasound has proven to be a useful decision-making technique, the greater the impact of which is seen the shorter the waiting time before it is performed.

Delivery of florfenicol in veterinary medicine through a PLGA-based nanodelivery system: improving its performance and overcoming some of its limitations.

As is the case with other veterinary antibiotics, florfenicol (FFC) faces certain limitations, such as low solubility in water, or the fact that it is reported to interfere with the immune response after some immunoprofilactic actions in livestock. Aiming to improve its efficacy and overall performance, FFC was loaded into a polymeric nanobased delivery system by succesfully using the emulsion-evaporation technique. The poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with FFC were characterized in terms of size (101 ± 0.52 nm), zeta potential (26.80 ± 1.30 mV) and poly-dispersity index (0.061 ± 0.019). The achieved loading was 2.24 µg FFC/mg of NPs, with an entrapment efficiency of 7.9%. The antimicrobial effect, the anti-biofilm formation and the cytotoxicity properties of the NPs were evaluated. The results indicated a MIC decreased by ~97.13% for S. aureus, 99.33% for E.coli and 64.1% for P. aeruginosa when compared to free FFC. The minimum inhibitory concentration (MIC) obtained indicated the potential for using a significantly lower dose of florfenicol. The delivery system produced biofilm inhibition while showing no cytotoxic effects when tested on porcine primary fibroblasts and horse mesenchymal stem cells. These findings suggest that florfenicol can be improved and formulations optimized for use in veterinary medicine through its incorporation into a nanobased delivery system designed to release in a controlled manner over time.

Elucidating the insecticidal mechanisms of zein nanoparticles on Anticarsia gemmatalis (Lepidoptera: Erebidae).

Previous research suggested that positively charged zein nanoparticles [(+)ZNP] were toxic to neonates of Anticarsia gemmatalis Hübner and deleterious to noctuid pests. However, specific modes of action for ZNP have not been elucidated. Diet overlay bioassays attempted to rule out the hypothesis that A. gemmatalis mortality was caused by surface charges from component surfactants. Overlay bioassays indicated that negatively charged zein nanoparticles [(-)ZNP] and its anionic surfactant, sodium dodecyl sulfate (SDS), exhibited no toxic effects when compared to the untreated check. Nonionic zein nanoparticles [(N)ZNP] appeared to increase mortality compared to the untreated check, though larval weights were unaffected. Overlay results for (+)ZNP and its cationic surfactant, didodecyldimethylammonium bromide (DDAB), were found to be consistent with former research indicating high mortalities, and thus, dosage response curves were conducted. Concentration response tests found the LC50 for DDAB on A. gemmatalis neonates was 208.82 a.i./ml. To rule out possible antifeedant capabilities, dual choice assays were conducted. Results indicated that neither DDAB nor (+)ZNP were antifeedants, while SDS reduced feeding when compared to other treatment solutions. Oxidative stress was tested as a possible mode of action, with antioxidant levels used as a proxy for reactive oxygen species (ROS) in A. gemmatalis neonates, which were fed diet treated with different concentrations of (+)ZNP and DDAB. Results indicated that both (+)ZNP and DDAB decreased antioxidant levels compared to the untreated check, suggesting that both (+)ZNP and DDAB may inhibit antioxidant levels. This paper adds to the literature on potential modes of action by biopolymeric nanoparticles.

Injectable Antioxidant and Oxygen-Releasing Lignin Composites to Promote Wound Healing.

The application of engineered biomaterials for wound healing has been pursued since the beginning of tissue engineering. Here, we attempt to apply functionalized lignin to confer antioxidation to the extracellular microenvironments of wounds and to deliver oxygen from the dissociation of calcium peroxide for enhanced vascularization and healing responses without eliciting inflammatory responses. Elemental analysis showed 17 times higher quantity of calcium in the oxygen-releasing nanoparticles. Lignin composites including the oxygen-generating nanoparticles released around 700 ppm oxygen per day at least for 7 days. By modulating the concentration of the methacrylated gelatin, we were able to maintain the injectability of lignin composite precursors and the stiffness of lignin composites suitable for wound healing after photo-cross-linking. In situ formation of lignin composites with the oxygen-releasing nanoparticles enhanced the rate of tissue granulation, the formation of blood vessels, and the infiltration of α-smooth muscle actin+ fibroblasts into the wounds over 7 days. At 28 days after surgery, the lignin composite with oxygen-generating nanoparticles remodeled the collagen architecture, resembling the basket-weave pattern of unwounded collagen with minimal scar formation. Thus, our study shows the potential of functionalized lignin for wound-healing applications requiring balanced antioxidation and controlled release of oxygen for enhanced tissue granulation, vascularization, and maturation of collagen.

Method for assessing coating uniformity of angioplasty balloons coated with poly(lactic-co-glycolic acid) nanoparticles loaded with quercetin.

Significance: Drug-coated angioplasty balloons (DCBs) are used to treat peripheral artery disease, and proper dosage depends on coating characteristics like uniformity and number of layers. Aim: Quantify coating uniformity and correlate fluorescence intensity to drug loading for DCBs coated with 5, 10, 15, or 20 layers of poly(lactic-co-glycolic acid) nanoparticles (NPs) entrapped with quercetin. Approach: Images of DCBs were acquired using fluorescence microscopy. Coating uniformity was quantified from histograms and horizontal line profiles, and cracks on the balloons were measured and counted. Fluorescence intensity was correlated with the drug loading of quercetin found from gravimetric analysis coupled with high-performance liquid chromatography (HPLC). Results: Higher numbers of coating layers on DCBs may be associated with less uniform coatings. Cracks in the coating were present on all balloons, and the length of cracks was not significantly different between balloons coated with different numbers of layers or balloons coated with the same number of layers. A strong positive correlation was identified between fluorescence intensity and drug loading. Conclusion: There may be a relationship between the number of NP layers and the uniformity of the coating, but further investigation is needed to confirm this. Fluorescence intensity appears to be a strong predictor of drug loading on DCBs coated with quercetin-entrapped NPs, demonstrating that fluorescent imaging may be a viable alternative to drug release studies.

Distinguishing nanoparticle drug release mechanisms by asymmetric flow field-flow fractionation.

This research demonstrates the development, application, and mechanistic value of a multi-detector asymmetric flow field-flow fractionation (AF4) approach to acquire size-resolved drug loading and release profiles from polymeric nanoparticles (NPs). AF4 was hyphenated with multiple online detectors, including dynamic and multi-angle light scattering for NP size and shape factor analysis, fluorescence for drug detection, and total organic carbon (TOC) to quantify the NPs and dissolved polymer in nanoformulations. The method was demonstrated on poly(lactic-co-glycolic acid) (PLGA) NPs loaded with coumarin 6 (C6) as a lipophilic drug surrogate. The bulk C6 release profile using AF4 was validated against conventional analysis of drug extracted from the NPs and complemented with high performance liquid chromatography - quadrupole time-of-flight (HPLC-QTOF) mass spectrometry analysis of oligomeric PLGA species. Interpretation of the bulk drug release profile was ambiguous, with several release models yielding reasonable fits. In contrast, the size-resolved release profiles from AF4 provided critical information to confidently establish the release mechanism. Specifically, the C6-loaded NPs exhibited size-independent release rate constants and no significant NP size or shape transformations, suggesting surface desorption rather than diffusion through the PLGA matrix or erosion. This conclusion was supported through comparative experimental evaluation of PLGA NPs carrying a fully entrapped drug, enrofloxacin, which showed size-dependent diffusive release, along with density functional theory (DFT) calculations indicating a higher adsorption affinity of C6 onto PLGA. In summary, the development of the size-resolved AF4 method and data analysis framework fulfills salient analytical gaps to determine drug localization and release mechanisms from nanomedicines.

Retention rate of secukinumab in psoriatic arthritis: Real-world data results from a Spanish multicenter cohort.

Secukinumab is a novel anti-IL17 biologic treatment approved for the treatment of psoriatic arthritis (PsA). The purpose of the present study is to identify factors that can condition the retention rate of this drug in a real-world scenario. Methods: A multicentric retrospective study was conducted based on the registries of consecutive patients diagnosed with PsA who started secukinumab from January 2016 to December 2018. For purposes of Cox-regression analysis, the time spanning from the first administration of secukinumab until its interruption or the end of the follow-up was considered the independent variable. Variables of known relevance and those who demonstrated direct association with the drug retention rate were included in the model. Results: One hundred seventy-six registries were analyzed (average age at diagnosis 44.7 ±â€…12.1 years old, 114 females). The median retention rate of secukinumab was 636 days (95% confidence interval [CI] 542.4-729.5). Presence of peripheral arthritis (hazard ratio 0.424 [95% CI 0.213-0.847, P = .015]) and a time of evolution >6 years (hazard ratio 0.468 [95% CI 0.225-0.975, P = .043]) were the 2 variables that showed a significant influence on the drug retention rate. According to our results, patients who exhibit peripheral arthritis and those with a higher evolution time will have more probabilities of a larger secukinumab retention rate.

Nanoparticle coatings for controlled release of quercetin from an angioplasty balloon.

Peripheral artery disease (PAD) is a systemic vascular disease of the legs that results in a blockage of blood flow from the heart to the lower extremities. Now one of the most common causes of mortality in the U.S., the first line of therapy for PAD is to mechanically open the blockages using balloon angioplasty. Coating the balloons with antiproliferative agents can potentially reduce vessel re-narrowing, or restenosis after surgical intervention, but current drug-coated balloons releasing chemotherapy agents like paclitaxel have in some cases shown increased mortality long-term. Our aim was to design a novel drug-coated balloon using a polymeric nanodelivery system for a sustained release of polyphenols that reduce restenosis but with reduced toxicity compared to chemotherapy agents. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles with entrapped quercetin, a dimethoxy quercetin (rhamnazin), as well as quercetin covalently attached to PLGA, were developed. Balloon catheters were coated with polymeric nanoparticles using an ultrasonic method, and nanoparticle characteristics, drug loading, coating uniformity and drug release were determined. The adhesion of nanoparticles to vascular smooth muscle cells and the antiproliferative effect of nano-delivered polyphenols were also assessed. Of the nanoparticle systems tested, those with covalently attached quercetin provided the most sustained release over a 6-day period. Although these particles adhered to cells to a smaller extent compared to other nanoparticle formulations, their attachment was resistant to washing. These particles also exhibited the greatest anti-proliferative effect. In addition, their attachment was not altered when the cells were grown in calcifying conditions, and in PAD tissue calcification is typically a condition that impedes drug delivery. Moreover, the ultrasonic coating method generated a uniform balloon coating. The polymeric nanoparticle system with covalently attached quercetin developed herein is thus proposed as a promising platform to reduce restenosis post-angioplasty.

Effect of Polymeric Nanoparticles with Entrapped Fish Oil or Mupirocin on Skin Wound Healing Using a Porcine Model.

The utilization of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with entrapped fish oil (FO) loaded in collagen-based scaffolds for cutaneous wound healing using a porcine model is unique for the present study. Full-depth cutaneous excisions (5 × 5 cm) on the pig dorsa were treated with pure collagen scaffold (control, C), empty PLGA NPs (NP), FO, mupirocin (MUP), PLGA NPs with entrapped FO (NP/FO) and PLGA NPs with entrapped MUP (NP/MUP). The following markers were evaluated on days 0, 3, 7, 14 and 21 post-excision: collagen, hydroxyproline (HP), angiogenesis and expressions of the COX2, EGF, COL1A1, COL1A3, TGFB1, VEGFA, CCL5 and CCR5 genes. The hypothesis that NP/FO treatment is superior to FO alone and that it is comparable to NP/MUP was tested. NP/FO treatment increased HP in comparison with both FO alone and NP/MUP (day 14) but decreased (p < 0.05) angiogenesis in comparison with FO alone (day 3). NP/FO increased (p < 0.05) the expression of the CCR5 gene (day 3) and tended (p > 0.05) to increase the expressions of the EGF (day 7, day 14), TGFB1 (day 21) and CCL5 (day 7, day 21) genes as compared with NP/MUP. NP/FO can be suggested as a suitable alternative to NP/MUP in cutaneous wound treatment.

Ultrasound changes following controlled mechanical stress in synovial tissue in the hands of healthy individuals.

OBJECTIVE: The physiological response of the synovium to acute mechanical stress has not been extensively studied. This response is interesting in terms of the morphological changes it can cause as any such changes should be taken into account during ultrasound examinations. The purpose of this study was to assess the extent of changes in ultrasound images of the synovial joint in the hands of healthy individuals after controlled mechanical stress. METHOD: We included 110 healthy volunteers on whom we carried out two ultrasound examinations of the non-dominant hand: one at baseline and the other after controlled handgrip exercise at 70% of the maximum voluntary contraction. RESULTS: The synovitis scores at baseline and after exercise were 0.472±0.798 and 0.772±1.162 t(109)=-3.791, respectively; p < 0.001. We observed no tenosynovitis in 88.2% of the participants at baseline, while after exercise the percentage fell to 70.9%; x2 (1, N=110) =10.0851, p = 0.0014. CONCLUSION: We conclude that synovitis and tenosynovitis are inducible by physical exercise and are detectable on ultrasound. This should be taken into account during ultrasound examinations for suspicion or follow-up of inflammatory rheumatism.

Life History of Chrysodeixis includens (Lepidoptera: Noctuidae) on Positively Charged Zein Nanoparticles.

Research indicates that nanoparticles can be an effective agricultural pest management tool, though unintended effects on the insect must be evaluated before their use in agroecosystems. Chrysodeixis includens (Walker) was used as a model to evaluate chronic parental and generational exposure to empty, positively charged zein nanoparticles ((+)ZNP) and methoxyfenozide-loaded zein nanoparticles (+)ZNP(MFZ) at low-lethal concentrations. To determine concentration limits, an acute toxic response test on meridic diet evaluated (+)ZNP(MFZ) and technical grade methoxyfenozide using two diet assay techniques. No differences in acute toxicity were observed between the two treatments within their respective bioassays. With these results, population dynamics following chronic exposure to low-lethal concentrations were evaluated. Parental lifetables evaluated cohorts of C. includens reared on diet treated with LC5 equivalents of (+)ZNP, (+)ZNP(MFZ), or technical grade methoxyfenozide. Compared to technical grade methoxyfenozide, (+)ZNP(MFZ) lowered both the net reproductive rate and intrinsic rate of increase, and was more deleterious to C. includens throughout its lifespan. This was contrasted to (+)ZNP, which showed no differences in population dynamics when compared with the control. To evaluate chronic exposure to (+)ZNP, generational lifetables reared cohorts of C. includens on LC5 equivalent values of (+)ZNP and then took the resulting offspring to be reared on either (+)ZNP or untreated diet. No differences in lifetable statistics were observed between the two treatments, suggesting that (+)ZNP at low ppm do not induce toxic generational effects. This study provides evidence into the effects of nanodelivered methoxyfenozide and the generational impact of (+)ZNP.

Impact of ultrasound on the perception of health quality in adult patients with rheumatoid arthritis / Impacto de la ecografía en la percepción de la calidad en salud de pacientes adultos con artritis reumatoide

ABSTRACT Introduction: Ultrasound has shown its usefulness in multiple aspects in the management of inflammatory joint disease and in particular of rheumatoid arthritis (RA). The evidence using patient outcomes and its aspects related to quality of health care is scarce. The aim of this study is to determine the level of satisfaction in the perception of the quality of health care in a group of patients with RA who underwent ultrasound during the consultation, and whether it is higher than those who did not have the ultrasound. Methods: An observational, cross-sectional descriptive study was performed. Patients older than 18 years with a diagnosis of RA using the ACR/EULAR classification criteria were included. One group underwent skeletal muscle ultrasound to study RA during the out-patient medical consultation, as decided by the attending physician. After the completion of the medical action according to prior verbal acceptance by the patient, the Servqhos questionnaire and an ultrasound questionnaire were completed. A satisfied patient was defined as one who had 70% or more in the responses in the Servqhos questionnaire greater than or equal to 4, and a score of 5 in this questionnaire was defined as maximum satisfaction. There were no significant differences between the number of satisfied patients in the two groups. Univariate analysis was performed according to the distribution in the ultrasound or non-performing groups. Subsequently, a bivariate analysis of the different questions was carried out according to the distribution in the satisfaction and very high satisfaction groups. It was established if there was any degree of association using the Chi squared test for categorical variables, and the parametric tests (Mann Whitney U) or non-parametric tests (Kruskal-Wallis test) for the numerical variables were performed according to the distribution. Results: A total of 126 patients were obtained, of whom 62 corresponded to the group of patients who underwent ultrasound during the consultation and 62 to the control group in whom no ultrasound was performed. The majority were women (91%). Ultrasound was mostly performed to study joint disease (93%), with a third of the time to assess more than one aspect. In those on whom the ultrasound was performed, the number of satisfied patients was 56 (90%) and for the control group it was 48 (77%). The difference in the proportion of satisfied patients (13%) was statistically significant (P = .05). A difference was found between the groups in the number of patients with the highest level of satisfaction in the questions regarding presentation of staff and technology (P < .05). The vast majority of patients considered that ultrasound was useful during the consultation (93%), and that it generates greater confidence in the treatments and the doctor (93%). Conclusions: Performing skeletal muscle ultrasound during consultation in patients with RA improves satisfaction rates of health care, perception of the doctor, and treatments.

RESUMEN Introducción: La ecografía ha mostrado su utilidad en múltiples aspectos del manejo de la enfermedad articular inflamatoria, particularmente en la artritis reumatoide (AR). Su utilidad usando desenlaces derivados de pacientes y relacionados con aspectos de la calidad de la atención en salud es escasa. El objetivo del estudio es determinar si el grado de satisfacción de la calidad de la atención en un grupo de pacientes con AR, en quienes se realizó ecografía durante la consulta, es superior al de un grupo en los que esta no se llevó a cabo. Métodos: Se realizó un estudio observacional, descriptivo transversal. Se incluyeron pacientes mayores de 18 años con diagnóstico de AR por criterios clasificatorios ACR/EULAR que posteriormente a la finalización del acto médico respondieron las preguntas del cuestionario Servqhos. Quienes se sometieron a ecografía musculoesquelética para estudio de AR durante la consulta ambulatoria, según decisión del médico tratante, respondieron adicionalmente el cuestionario de ecografía. Se define paciente satisfecho como aquel que tiene un 70% o más en las respuestas del cuestionario Servqhos con un puntaje mayor o igual a 4, y se define como la máxima satisfacción al puntaje de 5 en una pregunta de dicho cuestionario. Se determinó si había diferencias significativas entre las proporciones de pacientes satisfechos en los dos grupos con y sin ecografía. Se realizó un análisis univariado según la distribución en los grupos, y posteriormente se hizo un análisis bivariado de las diferentes preguntas según la distribución en los grupos de satisfacción y muy alta satisfacción. Se estableció si había algún grado de asociación con las pruebas de chi-cuadrado para las variables categóricas, en tanto que para las variables numéricas se llevaron a cabo pruebas paramétricas (U de Mann Whitnney) y no paramétricas (test de Kruskal-Wallis), según la distribución. Resultados: Se obtuvo un total de 126 pacientes, de los cuales 62 corresponden al grupo de aquellos en quienes se realizó ecografía durante la consulta, mientras que otros 62 hacen parte del grupo control, en quienes no se realizó ecografía. La mayoría eran mujeres (91%). En quienes se hizo la ecografía, el número de pacientes satisfechos fue de 56 (90%), en tanto que para el grupo control fue de 48 (77%). La diferencia en la proporción de pacientes satisfechos entre los grupos fue del 13%, siendo estadísticamente significativa (p = 0,05). Se encontró diferencia entre los grupos en las preguntas referentes a presentación del personal y la tecnología de los equipos (p < 0,05). La gran mayoría de los pacientes consideró que la ecografía fue útil durante la consulta (93%) y que genera mayor seguridad en los tratamientos y en el criterio médico (93%). Conclusiones: La realización de ecografía musculoesquelética durante la consulta en pacientes con AR mejora los índices de satisfacción de atención en salud, así como la percepción del criterio médico y de los tratamientos.

Evidence for the Use of Secukinumab in Patients with Radiographic and Non-radiographic Axial Spondyloarthritis in the Last 5 Years.

Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disorder that causes chronic pain, primarily in the spine and sacroiliac joints. It is characterized by the presence of type 1 major histocompatibility complex HLA-B27 genetic marker, arthritis in peripheral joints, enthesitis and/or dactylitis and extra-articular manifestations. Current guidelines recommend biological therapy when first-line therapy is not sufficiently effective. The finding that the interleukin (IL)-17 axis is vital for the pathogenesis of axSpA propelled the development of secukinumab, a fully human monoclonal antibody directed against IL-17A. The present review provides evidence on the efficacy and safety of secukinumab in the treatment of radiographic and non-radiographic axSpA from nine randomized controlled phase III trials, as well as evidence from real-world observational analyses. The primary endpoint in six clinical trials was the proportion of patients meeting the Assessment of SpondyloArthritis international Society criteria for either 20% or 40% improvement (ASAS20, ASAS40) at week 16. Significantly more patients achieved the primary endpoint with secukinumab compared with placebo in all the studies except MEASURE 4. Both clinical trials and real-world studies showed significant improvements in the secondary endpoints of disease activity, quality of life, and pain and fatigue relative to placebo. The benefits of secukinumab were generally sustained during longer-term (up to 5 years) treatment. Overall, secukinumab was well tolerated with a low frequency of adverse events and treatment persistence was high in the real-world setting. Although indirect comparisons suggest that secukinumab and adalimumab have comparable efficacy and safety, they are being directly compared in the ongoing SURPASS study. During the current coronavirus disease 2019 (COVID-19) pandemic, it is advisable to continue biological therapy in patients who do not have severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, but interrupt treatment during an infection, reinitiating once the patient has recovered from the infection. In conclusion, secukinumab is a largely safe and effective treatment for radiographic and non-radiographic axSpA.

Determinants of therapeutic success of corticoids injections in trigger finger syndrome.

BACKGROUND AND OBJECTIVE: Trigger finger is a frequent complaint in which corticosteroid infiltrations play a relevant therapeutic role in intermediate degrees of severity when conservative treatment has not worked. However, there are no criteria to select which patients will benefit most from this procedure. The present study aimed to identify the factors leading to the therapeutic success of corticosteroid infiltration in these patients. MATERIALS AND METHODS: We designed a prospective longitudinal study based on routine clinical practice with adult patients with a clinical diagnosis of trigger finger grade II or III on the Quinnell scale, who underwent an infiltration of 20 mg of triamcinolone acetate. The outcome variables were to achieve a Quinnell grade I or reduce the severity of the symptoms by at least one category two months after the procedure. To identify the determinants of complete or partial therapeutic success, binary logistic regression predictive modelling was performed using those variables that had a satisfactory univariate correlation. RESULTS: 74 patients were included over three years, 42 of whom (61.8%) were classified as Quinnell grade III. After infiltration, 22 (32.4%) achieved complete resolution and 50 (73.5%) partial resolution. The variables tendon thickening (HR 10.72; 95%CI 2.88-39.93; P < .001) and progression time (HR 1.23; 95%CI 1.02-1.49; P = .027) proved to be predictors of therapeutic success in complete resolution. For the modelling for partial resolution, the same variables proved to be determining predictors (HR 5.57; 95%CI 1.38-22.41; P = .016 and HR 1.18; 95%CI .99-1.41; P = .051, respectively). Pulley thickening did not demonstrate predictive ability in either model. DISCUSSION AND CONCLUSIONS: Our results indicate that the demonstration of finger flexor apparatus thickening is the main determining factor for the success of corticosteroid infiltrations in this pathology. This is in agreement with the histological findings of specimens obtained from both tenosynovial and pulley tissue. In the former, in addition to an infiltrate of inflammatory characteristics, the presence of chondrocytoid cells producing hyaluronic acid is demonstrated. Although the therapeutic success of infiltrations in previous studies reaches 70%, the recurrence rate is similar after 12 months. The selection of patients with tendon thickening ensures therapeutic success in the short term, could reduce recurrence in the long term, and avoid delay in release surgery.