Transfusion independence after lenalidomide discontinuation in patients with del(5q) myelodysplastic neoplasm: a HARMONY Alliance study.

Lenalidomide (LEN) can induce red blood cell-transfusion independence (RBC-TI) in 60-70% of del(5q) myelodysplastic neoplasm (MDS) patients. Current recommendation is to continue LEN in responding patients until failure or progression, with likelihood of toxicity and a high cost for healthcare systems. This HARMONY Alliance study investigated the outcome of MDS del(5q) patients who discontinued LEN while RBC-transfusion independent. We enrolled 118 patients with IPSS-R low-intermediate risk. Seventy patients (59%) discontinued LEN for intolerance, 38 (32%) per their physician decision, nine (8%) per their own decision and one (1%) for unknown reasons. After a median follow-up of 49 months from discontinuation, 50/118 patients lost RBC-TI and 22/30 who underwent cytogenetic re-evaluation lost complete cytogenetic response. The median RBC-TI duration was 56 months. In multivariate analysis, RBC-TI duration after LEN discontinuation correlated with low transfusion burden before LEN therapy, treatment ≥ 12 LEN cycles, younger age and higher Hb level at LEN withdrawal. Forty-eight patients were re-treated with LEN for loss of response and 28 achieved again RBC-TI. These data show that stopping LEN therapy in MDS del(5q) patients who reached RBC-TI allows prolonged maintenance of TI in a large subset of patients.

A bibliometric and citation network analysis of crosslinking.

Purpose: Research on crosslinking has focused mainly on trying to slow the progression of keratoconus. The objective of this bibliometric analysis is to determine the relationships between the different publications and authors. As well as to identify the different areas of research on crosslinking. Methods: Web of Science (WOS) was the database for the search of publications for the period 1972 to December 2023, using the terms: crosslinking, cross-linking, ocular, vision, visual, cornea, ectasia AND Keratoconus. The analysis of the publication was performed using the CitNetExplorer, VOSviewer and CiteSpace software. Results: 7161 publications and 59415 citation networks were found. The year with the most publications is 2021, a total of 571 (7.97%) publications and 135 citation networks. The most cited publication was "Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus" published by Wollensak et al. in 2003, with a citation index of 1780. Using the Clustering function, five groups were found that cover the main research areas in this field: keratoconus, corneal transplantation, cataracts, corneal inflammation and axial growth. Conclusion: The treatment of keratoconus continues to be the topic of interest in this area of research. However, in recent years there has been an increase in research on how crosslinking helps to slow down axial growth.

Efficacy assessment of liposome crosslinked hyaluronic acid and standard hyaluronic acid eye drops for dry eye disease management: a comparative study employing the ocular surface analyzer and subjective questionnaires.

Introduction: Dry eye disease (DED) is a prevalent condition causing ocular discomfort and visual disturbances, often managed with artificial tears. This study aimed to assess and compare the efficacy of eye drops containing Crosslinked Hyaluronic Acid (CHA) with liposomes and crocin and standard Hyaluronic Acid (HA) for DED management. Methods: A single-blind, longitudinal study was conducted on 24 participants (48 eyes), randomized to receive one of the two treatments. Ocular health measures, including the ocular surface disease index (OSDI) and the standard patient evaluation of eye dryness (SPEED) scores, were assessed at baseline and 6 weeks post-treatment using the Ocular Surface Analyzer. Results: CHA achieved a lipid layer thickness increase of 1.29 ± 1.08 Guillon pattern degree (p < 0.01), FNIBUT increase 0.64 ± 0.77 s (p < 0.01), MNIBUT increase1.28 ± 4.74 s (p = 0.19), OSDI decrease 11.72 ± 6.73 score points (p < 0.01) and SPEED decrease 1.16 ± 5.05 score points (p = 0.27). Significant reductions in the OSDI and SPEED scores post-treatment were observed with both treatments, indicating their effectiveness. Conclusion: CHA with liposomes exhibits superior efficacy compared to standard HA eye drops in the management of DED. These findings highlight the potential for personalized treatment strategies incorporating CHA, indicating a more effective approach to DED management. However, further research is required to validate these results and investigate the long-term effects, which may pave the way for a data-driven and optimized approach to managing DED.

Space, the final frontier: The spatial component of phytoplankton-bacterial interactions.

Microscale interactions between marine phytoplankton and bacteria shape the microenvironment of individual cells, impacting their physiology and ultimately influencing global-scale biogeochemical processes like carbon and nutrient cycling. In dilute environments such as the ocean water column, metabolic exchange between microorganisms likely requires close proximity between partners. However, the biological strategies to achieve this physical proximity remain an understudied aspect of phytoplankton-bacterial associations. Understanding the mechanisms by which these microorganisms establish and sustain spatial relationships and the extent to which spatial proximity is necessary for interactions to occur, is critical to learning how spatial associations influence the ecology of phytoplankton and bacterial communities. Here, we provide an overview of current knowledge on the role of space in shaping interactions among ocean microorganisms, encompassing behavioural and metabolic evidence. We propose that characterising phytoplankton-bacterial interactions from a spatial perspective can contribute to a mechanistic understanding of the establishment and maintenance of these associations and, consequently, an enhanced ability to predict the impact of microscale processes on ecosystem-wide phenomena.

Sinus fungal balls caused by Syncephalastrum spp.: 2 clinical cases and literature review.

INTRODUCTION: Syncephalastrum spp. is a mucoral that rarely produces pathology. Fungal balls caused by this genus are infrequent. It requires early diagnosis and treatment to avoid associated morbidity and mortality. METHODS: We describe two clinical cases of sinus fungus balls caused by Syncephalastrum spp. and review the literature. RESULTS: Two patients were treated for sinus fungus balls. When their samples were analysed, the aetiology was determined to be Syncephalastrum spp. A case of pulmonary fungus ball due to Syncephalastrum spp. is described in the literature. All cases, including these described in the present study, had a good evolution after treatment. CONCLUSIONS: Syncephalastrum spp. is a filamentous fungus that should be considered as an aetiology of sinus fungus ball.

Identifying priority sites for whale shark ship collision management globally.

The expansion of the world's merchant fleet poses a great threat to the ocean's biodiversity. Collisions between ships and marine megafauna can have population-level consequences for vulnerable species. The Endangered whale shark (Rhincodon typus) shares a circumglobal distribution with this expanding fleet and tracking of movement pathways has shown that large vessel collisions pose a major threat to the species. However, it is not yet known whether they are also at risk within aggregation sites, where up to 400 individuals can gather to feed on seasonal bursts of planktonic productivity. These "constellation" sites are of significant ecological, socio-economic and cultural value. Here, through expert elicitation, we gathered information from most known constellation sites for this species across the world (>50 constellations and >13,000 individual whale sharks). We defined the spatial boundaries of these sites and their overlap with shipping traffic. Sites were then ranked based on relative levels of potential collision danger posed to whale sharks in the area. Our results showed that researchers and resource managers may underestimate the threat posed by large ship collisions due to a lack of direct evidence, such as injuries or witness accounts, which are available for other, sub-lethal threat categories. We found that constellations in the Arabian Sea and adjacent waters, the Gulf of Mexico, the Gulf of California, and Southeast and East Asia, had the greatest level of collision threat. We also identified 39 sites where peaks in shipping activity coincided with peak seasonal occurrences of whale sharks, sometimes across several months. Simulated collision mitigation options estimated potentially minimal impact to industry, as most whale shark core habitat areas were small. Given the threat posed by vessel collisions, a coordinated, multi-national approach to mitigation is needed within priority whale shark habitats to ensure collision protection for the species.

Prevalence and Estimation of the Evolution of Myopia in Spanish Children.

Background: In recent decades, myopia has turned into a public health issue across the world. Between 1993 and 2016, the percentage of myopes increased from 10.4% to 34.2%. This study aims to analyze the myopia prevalence in Spanish children from five to seven years old over the last five years and to predict the rate of myopia in Spain by 2030. Methods: The sample consisted of children aged between 5 and 7, who underwent an optometric examination consisting of the measurement of visual acuity (VA) and determination of objective and subjective refraction. The cut-off points to define refractive error are established by the spherical equivalent (SE) value: hyperopia for an SE over or equal to +0.50 D; myopia for an SE under or equal to -0.50 D; and emmetropia when the SE is between -0.50 D and +0.50 D. Results: The myopia rate in Spanish children aged between five and seven was 19%. Myopia prevalence progressively increased as children grew up (p ≤ 0.001). It is estimated that, in the year 2030, the rate of myopia will be 30.2% [CI: 25.3-35.0], of which 81.9% [CI: 78.3-85.3] will have low myopia, 10.0% [CI: 7.2-12.8] moderate myopia, and 7.3% [CI: 4.9-9.7] high myopia. Conclusions: Nineteen percent of Spanish children between five and seven are myopes. In 2030, is expected that 30.2% of Spanish children between 5 and 7 years of age will be myopes. These estimations will support eye care professionals in recommending that children spend more time outdoors to prevent the onset of myopia and the use of methods to control myopia to avoid reaching these figures of high myopia.

Effectiveness of a Spectacle Lens with a Specific Asymmetric Myopic Peripheral Defocus: 12-Month Results in a Spanish Population.

BACKGROUND: Different designs of ophthalmic lenses have been studied to control the progression of myopia in children. This study aims to evaluate the short-term efficacy of a new design of ophthalmic lens with asymmetric myopic peripheral defocus (MPDL) on myopia progression in children compared to a control group wearing a single-vision lens (SVL). METHODS: Children aged 5 to 12 with myopia up to -0.50 D, astigmatism and anisometropia under 1.50 D, and corrected visual acuity over 20/20 were randomized to either the study group (MPDL) or control group (SVL). The myopia progression was evaluated by measuring axial length (AL) growth (IOL Master; Zeiss) over a period of one year. RESULTS: Ninety-two subjects were recruited. Forty-six children were randomly assigned to the control group, and 46 to the study group. In total, 83 children completed the clinical trial, with a mean age of 10.81 [9.53-11.92] years, among which 59.04% were female. After one year of treatment, there was less AL elongation in the study group compared to the control group (0.16 ± 0.16 mm vs. 0.24 ± 0.16 mm, p = 0.034). CONCLUSIONS: The MPDL significantly reduced the absolute growth of AL by 39% (p = 0.014) and relative growth of AL by 37.3% (p = 0.012) after 12 months in comparison to the control group in a Spanish population.

Assessing the rebound phenomenon in different myopia control treatments: A systematic review.

PURPOSE: To review the rebound effect after cessation of different myopia control treatments. METHODS: A systematic review that included full-length randomised controlled studies (RCTs), as well as post-hoc analyses of RCTs reporting new findings on myopia control treatments rebound effect in two databases, PubMed and Web of Science, was performed according to the PRISMA statement. The search period was between 15 June 2023 and 30 June 2023. The Cochrane risk of bias tool was used to analyse the quality of the selected studies. RESULTS: A total of 11 studies were included in this systematic review. Unifying the rebound effects of all myopia control treatments, the mean rebound effect for axial length (AL) and spherical equivalent refraction (SER) were 0.10 ± 0.07 mm [-0.02 to 0.22] and -0.27 ± 0.2 D [-0.71 to -0.03] after 10.2 ± 7.4 months of washout, respectively. In addition, spectacles with highly aspherical lenslets or defocus incorporated multiple segments technology, soft multifocal contact lenses and orthokeratology showed lower rebound effects compared with atropine and low-level light therapy, with a mean rebound effect for AL and SER of 0.04 ± 0.04 mm [0 to 0.08] and -0.13 ± 0.07 D [-0.05 to -0.2], respectively. CONCLUSIONS: It appears that the different treatments for myopia control produce a rebound effect after their cessation. Specifically, optical treatments seem to produce less rebound effect than pharmacological or light therapies. However, more studies are required to confirm these results.

Job satisfaction of Spanish and Portuguese optometrists.

PURPOSE: Given the increase in demand for optometry services by society and the importance of the Optometry profession in Portugal and Spain, the objective of this study was to determine job satisfaction and important factors related to this satisfaction in a sample of Portuguese and Spanish optometrists. METHODS: A prospective, cross-sectional, and observational study was carried out from June to December 2021. An adaptation of the 15-item job satisfaction in eye-care personnel (JSEP) questionnaire validated by Paudel et al. was administered to Portuguese and Spanish optometrists. The questionnaire was shared through different social media (Facebook, LinkedIn, WhatsApp, etc.) in a Google form during the months of June to December 2021 in Portugal and Spain. RESULTS: A total of 530 surveys were collected in Portugal (42.3%; n = 224) and Spain (57.7%; n = 306). The factors that most influence overall job satisfaction are salary, career development opportunities, recognition/prestige in society, good work-life balance (all p<0.001), workplace equipment and facilities, and encouragement reward positive feedback (both p = 0.002). When comparing the determinants of job satisfaction of optometrists, it was found that Portuguese professionals were generally more satisfied than Spanish ones (p<0.001). However, Spanish optometrists reported feeling more supported by their colleagues (p<0.001). CONCLUSION: This study has shown that the level of job satisfaction was higher in Portugal than in Spain. The most important factors influencing job satisfaction were salary, job stability, and support from colleagues.

Strategies and attitudes on the management of myopia in clinical practice in Spain - 2022 update.

OBJECTIVE: This study analyses strategies and attitudes on myopia management reported by eye care practitioners (ECP) from Spain in 2022. METHODS: A questionnaire was distributed to ECPs worldwide via the internet through professional associations. The questionnaire was distributed by email to all registered Spanish optician-optometrists. Questions examined awareness of increasing myopia prevalence; perceived efficacy; uptake of available approaches; and reasons preventing further uptake of specific approaches. RESULTS: Of 3,107 practitioners who participated in the study, 380 were Spanish ECPs. Using a 10-point scale, Spanish practitioners reported less concern about increasing pediatric myopia (8.3 ± 1.6) compared to ECP's worldwide (8.5 ± 1.9) (p < 0.001), but similar level of clinical activity in myopia control (7.8 ± 2.3 vs. 7.5 ± 2.5, respectively) (p > 0.05); however, around half of all prescribed treatments were single-vision distance spectacles/contact lenses both in Spain and in most regions, with Spanish practitioners prescribing less single-vision spectacles than African and Asian (p < 0.001), but more than Australasian practitioners (p = 0.04). No significant differences were found between Spain and the other regions in the perceived efficacy of combined therapy, orthokeratology, and outdoor time (p > 0.05), with the former being perceived as the most effective myopia control method followed by orthokeratology. No significant differences were found between Spain and the world's average in factors preventing the prescription of myopia control approaches (p > 0.05). Spanish practitioners reported that embracing myopia management has a positive, but lower impact on customer loyalty, practice revenue and job satisfaction compared with the other regions (all p < 0.001). CONCLUSIONS: Myopia control is increasing, although around half of practitioners still prescribe single-vision distance spectacles/contact lenses to young/progressive myopes. Combined therapy followed by orthokeratology were perceived as the most effective treatments. Embracing myopia management improved patient loyalty and job satisfaction.

Citation network analysis on keratoconus.

OBJECTIVE: The high incidence of keratoconus has caused its management, etiology, and pathogenesis to be controversial topics in the ophthalmology field. This study aims to analyze the relationship between the different publications and authors through citation networks, as well as to identify the research areas and determine the most cited article. METHODS: The search for publications was carried out through the Web of Science database, using the term "Keratoconus" between 1900 and December 2022. The Citation Network Explorer and CiteSpace software were used for the publication analysis. RESULTS: 9,655 publications were found, with 124,379 citations generated on the network. The year with the highest number of publications was 2021. The most cited publication was "Keratoconus" by Rabinowitz, published in 1998. Cluster function gave five groups of research areas about keratoconus: corneal signs and parameters, cross-linking efficiency and effects, clinical factors, keratoplasty, and treatment. CONCLUSIONS: The citation network offers an objective and comprehensive analysis of the papers on keratoconus.

Trehalose and Dry Eye Disease: A Comprehensive Systematic Review of Randomized Controlled Trials.

The purpose of the research project was to extensively review the efficacy and safety of a trehalose tear-substitute treatment in cases of dry eye disease (DED). A systematic review that included only full-length randomized controlled studies (RCTs) reporting the effects of trehalose tear-substitute treatment in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The search period included papers published before 8 August 2023. The Cochrane risk-of-bias tool was used to analyze the quality of the studies selected. A total of 10 RCTs were included in this systematic review. Trehalose tear-substitute treatments achieved a higher improvement than did control group interventions in all reported variables. The mean differences between both groups were in favor of trehalose, and were as follows: ocular surface disease index (OSDI) questionnaire score of -8.5 ± 7 points, tear film breakup time (TBUT) of 1.9 ± 1 s, tear film thickness (TFT) of 0.25 ± 0.1 µm, tear meniscus height (TMH) of 0.02 ± 0.02 mm, Schirmer test (ST) of 0.8 ± 1.4 mm, corneal fluorescein staining (CFS) of -0.7 ± 0.1 points and visual acuity (VA) of 0.3 ± 2.1 letters. No adverse events after trehalose tear-substitute treatments were reported. Trehalose tear substitutes are a safe and effective treatment for DED. Therefore, trehalose tear substitutes should be recommended for patients with dry eye disease. In addition, there is specific evidence to support its use in the preoperative cataract surgery period.

Subjective behavioral measures in myopic and pre-myopic children before and after the COVID lockdown.

Background: There are environmental factors that may contribute to the onset of myopia. This study aims to evaluate the children's lifestyle changes before and after the COVID-19 lockdown and how they can influence their vision. Methods: The same questionnaire was administered to children aged between 5 and 7 in Spain every year in September before (2017-2019) and after the COVID-19 lockdown (2020-2021). All the children also passed a vision exam consisting of the measurement of visual acuity (VA) and determination of objective and subjective refraction. Children were classified as myopes, pre-myopes, or hyperopes. The cut-off points to define the refractive error were established according to the value of the spherical equivalent (SE): hyperopia (SE > +0,75D), myopia (SE ≤ -0,5D), or pre-myopia (-0.5D < SE ≥ +0.75D). Data analysis is performed with the SPSS 27.0 software (SPSS Inc., Chicago, Illinois). Results: In the pre-COVID period, the pre-myopes were the ones who spent the longest time outdoors, and after the COVID lockdown, there were no differences between groups. There neither were any differences in the time spent doing near-work activities between the groups in both periods (p > 0.05). Regarding the spherical equivalent, in the pre-COVID period, the mean value was 0.75 ± 2.09D and after the COVID lockdown, it was 0.47 ± 1.88D (p < 0.001). Conclusion: Pre-myopes spent more time outdoors than myopes in the pre-COVID period, while myopes spent more time using digital devices. All these differences do not exist after the COVID lockdown, with a general increase in the time spent outdoors and a decrease in the use of digital devices. Further studies are needed to know if these lifestyle changes remain and how they influence the onset of myopia.

Antimicrobial Mechanisms and Preparation of Antibiotic-impregnated Cement-coated Locking Plates in the Treatment of Infected Non-unions.

Background: Antibiotic-impregnated cement-coated plates (ACPs) have been used successfully for temporary internal fixation between stages in the two-stage treatment of infected non-unions. We describe our approach of using an ACP in the staged treatment of a methicillin-resistant Staphylococcus aureus (MRSA)-infected distal femoral non-union below a total hip prosthesis. In addition, we present the results of an in vitro experiment to provide an in-depth insight into the capacity of ACPs in (i) treating residual biofilm and (ii) preventing bacterial recolonisation. Materials and methods: In the first stage, we used a titanium LISS plate coated with hand-mixed PALACOS with vancomycin (PAL-V) for temporary internal fixation combined with commercially prepared COPAL with gentamicin and vancomycin (COP-GV) to fill the segmental defect. In the second stage, the non-union was treated with double-plate fixation and bone grafting.A Kirby-Bauer agar disc diffusion assay was performed to determine the antimicrobial activity of both ACPs and a drug-release assay to measure antibiotic release over time. A biofilm killing assay was also carried out to determine if the antibiotic released was able to reduce or eradicate biofilm of the patient's MRSA strain. Results: At one-year follow-up, there was complete bone-bridging across the previous non-union. The patient was pain-free and ambulatory without need for further surgery. Both ACPs with COP-GV and PAL-V exerted an antimicrobial effect against the MRSA strain with peak concentrations of antibiotic released within the first 24 hours. Concentrations released from COP-GV in the first 24 hours in vitro caused a 7.7-fold log reduction of colony-forming units (CFU) in the biofilm. At day 50, both COP-GV and PAL-V still released concentrations of antibiotic above the respective minimal inhibitory concentrations (MIC), likely contributing to the positive clinical outcome. Conclusion: The use of an ACP provides stability and infection control in the clinical scenario of an infected non-union. This is confirmed in vitro where the release of antibiotics from ACPs is characterised by an early burst followed by a prolonged sustained release above the MIC until 50 days. The burst release from COP-GV reduces CFU in the biofilm and prevents early recolonisation through synergistic activity of the released vancomycin and gentamicin. Clinical significance: An antibiotic-impregnated cement-coated plate is a useful addition to the surgeon's armamentarium to provide temporary internal fixation without the disadvantages of external fixation and contribute to infection control in an infected non-union. How to cite this article: Wagner RK, Guarch-Pérez C, van Dam AP, et al. Antimicrobial Mechanisms and Preparation of Antibiotic-impregnated Cement-coated Locking Plates in the Treatment of Infected Non-unions. Strategies Trauma Limb Reconstr 2023;18(2):73-81.

Clinical Evaluation of MyoCare in Europe (CEME): study protocol for a prospective, multicenter, randomized, double-blinded, and controlled clinical trial.

BACKGROUND: Myopia prevalence has been increasing in the last decades, and its pathological consequences, including myopic maculopathy and high myopia-associated optic neuropathy, are now one of the most common causes of visual impairment. It is estimated that by 2050, more than 50% of Europeans and Americans will be myopes, which is alarming due to the high morbidity of myopes over - 6.00D. Once myopia has appeared, there are different options with scientific evidence to try to slow the axial length growth. Ophthalmic lenses are the less invasive treatment to control myopia, and there is evidence about the efficacy of different designs, mainly in the Asiatic population. However, new designs have been launched, and it is not known if efficacy is the same between Asiatic and European subjects. Thus, we have set up a randomized, controlled, double-blind, and multicenter trial to investigate the efficacy of a new design of ophthalmic lenses for myopia control in European children. METHODS: A 2-year prospective, multicenter, randomized controlled, and double-blind clinical trial is used to investigate the efficacy of a new design of ophthalmic lenses to slow the progression of myopia. Three hundred children aged from 6 to 13 years old will be recruited and randomly assigned to a study or control group. The study group will be composed of 150 children wearing MyoCare while the control group will be composed of 150 children wearing Clearview. The inclusion criteria will be myopia with a spherical equivalent between - 0.75D and - 5.00D, astigmatism < 1.50D, and anisometropia < 1.00D and having a historical evolution of at least - 0.50 The primary outcome is to compare the mean annual progression of the spherical equivalent between both groups. The secondary outcomes are axial length, choroidal thickness, phorias, and accommodative status of both groups. DISCUSSION: This study will be the first randomized and controlled clinical trial in European children with spectacle lenses based on simultaneous competing defocus. The results will shed light on the clinical evidence of spectacle lenses relying on this new design for the management of myopia with results of efficacy in the non-Asiatic population. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT) 2022-001696. Registered on 27 April 2022. CLINICALTRIALS: gov NCT05919654. Registered on 26 June 2023.

3D-printed wound dressings containing a fosmidomycin-derivative prevent Acinetobacter baumannii biofilm formation.

Acinetobacter baumannii causes a wide range of infections, including wound infections. Multidrug-resistant A. baumannii is a major healthcare concern and the development of novel treatments against these infections is needed. Fosmidomycin is a repurposed antimalarial drug targeting the non-mevalonate pathway, and several derivatives show activity toward A. baumannii. We evaluated the antimicrobial activity of CC366, a fosmidomycin prodrug, against a collection of A. baumannii strains, using various in vitro and in vivo models; emphasis was placed on the evaluation of its anti-biofilm activity. We also developed a 3D-printed wound dressing containing CC366, using melt electrowriting technology. Minimal inhibitory concentrations of CC366 ranged from 1 to 64 µg/mL, and CC366 showed good biofilm inhibitory and moderate biofilm eradicating activity in vitro. CC366 successfully eluted from a 3D-printed dressing, the dressings prevented the formation of A. baumannnii wound biofilms in vitro and reduced A. baumannii infection in an in vivo mouse model.