Early-Phase Perceptions of COVID-19's Impact on Ophthalmology Practice Patterns: A Survey from the Pan-American Association of Ophthalmology.

Purpose: The COVID-19 pandemic affected medical practice worldwide due to interventions to prevent spreading. Its effect on ophthalmology practices in Latin America has not yet been explored. We aimed to assess the perceptions about the pandemic from countries' ophthalmological national and subspecialty retina societies affiliated to the Pan-American Association of Ophthalmology (PAAO). Patients and Methods: A survey-based study of leaders of national ophthalmological and retinal societies was conducted. The survey was sent by email to 30 societies, from which 20 responded (12 countries, 66.6% response rate). It included closed- and open-ended questions about (1) operational capacity and precautions, (2) telemedicine and virtual care, (3) procedures, and (4) post-pandemic considerations. Results: There was a marked decline in ophthalmology patient visits (80-95%) and elective surgeries (90%) during 2020 compared to before the pandemic. Precautions like temperature checks, mask usage, and social distancing were widely implemented while personal protective equipment (PPE) availability varied. Telemedicine use was limited due to lack of experience with it. Reopening plans focused on maintaining precautions and gradually resuming activities. Economic and security concerns were raised, and adherence to guidelines was emphasized. Respondents acknowledged the need to adapt to a "new normal". Long duration drugs, fewer imaging studies, and shorter wait times were preferred; however, availability of long duration drugs was limited. Conclusion: The pandemic impacted ophthalmology in Latin America, with reduced patient visits, procedures, and surgeries. Delayed treatment and complications were likely the result of the pandemic.

[Prenatal rescue dose of betamethasone in the preterm infant with intrauterine growth restriction]. / Dosis prenatal de rescate de betametasona en el prematuro con restricción del crecimiento intrauterino.

Antenatal corticosteroids reduce mortality and respiratory distress syndrome (RDS) in preterm newborns. These benefits decrease after a week of administration, recommending a rescue therapy if there is a new threat of premature delivery. Repeated administration of antenatal corticosteroids may have deleterious effects and their benefits are controversial in intrauterine growth restriction (IUGR). OBJECTIVE: to verify the effects in the IUGR population of antenatal betamethasone rescue therapy on neonatal morbidity and mortality, RDS, and neurodevelopment at 2 years. PATIENTS AND METHOD: Retrospective study including ≤ 34 weeks and ≤ 1,500g preterm newborns divided according to antenatal betamethasone exposure: Single-cycle (2 doses) vs Rescue therapy (3 doses). Subgroups were created for those ≥ 30 weeks. Both cohorts were followed up to 24 months of corrected age. The Ages & Stages Questionnaires (ASQ)® was administered to assess neurodevelopment. RESULTS: 62 preterm infants with a diagnosis of IUGR were included. The rescue therapy group compared with the single-dose group showed no differences in morbidity and mortality and less intubation rate at birth (p = 0.02), with no differences in respiratory support at 7 days of life. Preterm newborns ≥ 30 weeks exposed to rescue therapy showed higher morbidity and mortality (p = 0.03) and bronchopulmonary dysplasia (BPD) (p = 0.02), showing no differences in RDS. The rescue therapy group showed worse mean scores on the ASQ-3 scale, with no significant differences in cerebral palsy or sensory deficits. CONCLUSIONS: Rescue therapy reduces intubation at birth but does not reduce morbidity and mortality. However, at > 30 weeks, this benefit is not observed and the IUGR population exposed to rescue therapy presented more BPD and lower scores on the ASQ-3 scale at 2 years. Future studies should be aimed at the individualization of antenatal corticosteroid therapy.

A prognostic model based on gene expression parameters predicts a better response to bortezomib-containing immunochemotherapy in diffuse large B-cell lymphoma.

Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of aggressive lymphoma. Approximately 60% of fit patients achieve curation with immunochemotherapy, but the remaining patients relapse or have refractory disease, which predicts a short survival. Traditionally, risk stratification in DLBCL has been based on scores that combine clinical variables. Other methodologies have been developed based on the identification of novel molecular features, such as mutational profiles and gene expression signatures. Recently, we developed the LymForest-25 profile, which provides a personalized survival risk prediction based on the integration of transcriptomic and clinical features using an artificial intelligence system. In the present report, we studied the relationship between the molecular variables included in LymForest-25 in the context of the data released by the REMoDL-B trial, which evaluated the addition of bortezomib to the standard treatment (R-CHOP) in the upfront setting of DLBCL. For this, we retrained the machine learning model of survival on the group of patients treated with R-CHOP (N=469) and then made survival predictions for those patients treated with bortezomib plus R-CHOP (N=459). According to these results, the RB-CHOP scheme achieved a 30% reduction in the risk of progression or death for the 50% of DLBCL patients at higher molecular risk (p-value 0.03), potentially expanding the effectiveness of this treatment to a wider patient population as compared with other previously defined risk groups.

Failure of early non-invasive ventilation in preterm infants with respiratory distress syndrome in current care practice in Spanish level-III neonatal intensive care units - a prospective observational study.

Introduction: Despite advances in respiratory distress syndrome (RDS) management over the past decade, non-invasive ventilation (NIV) failure is frequent and associated with adverse outcomes. There are insufficient data on the failure of different NIV strategies currently used in clinical practice in preterm infants. Methods: This was a prospective, multicenter, observational study of very preterm infants [gestational age (GA) <32 weeks] admitted to the neonatal intensive care unit for RDS that required NIV from the first 30 min after birth. The primary outcome was the incidence of NIV failure, defined as the need for mechanical ventilation for <72 h of life. Secondary outcomes were risk factors associated with NIV failure and complication rates. Results: The study included 173 preterm infants with a median GA of 28 (IQR 27-30) weeks and a median birth weight of 1,100 (IQR 800-1,333) g. The incidence of NIV failure was 15.6%. In the multivariate analysis, lower GA (OR, 0.728; 95% CI, 0.576-0.920) independently increased the risk of NIV failure. Compared to NIV success, NIV failure was associated with higher rates of unfavorable outcomes, including pneumothorax, intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, and a combined outcome of moderate-to-severe bronchopulmonary dysplasia or death. Conclusion: NIV failure occurred in 15.6% of the preterm neonates and was associated with adverse outcomes. The use of LISA and newer NIV modalities most likely accounts for the reduced failure rate. Gestational age remains the best predictor of NIV failure and is more reliable than the fraction of inspired oxygen during the first hour of life.

A practical approach to dental care for patients with Wolf-Hirschhorn syndrome.

Wolf-Hirschhorn syndrome is a polymalformative chromosomal disorder caused by a deletion in the distal region of the short arm of chromosome 4. The disease is considered rare (1/50,000 births) and predominantly affects females (2:1). In addition to the characteristic facial phenotype ("Greek warrior helmet"), its clinical manifestations include epilepsy, developmental and psychomotor delay, intellectual disability, cardiac and respiratory complications, and eating problems. The most prevalent oral manifestations are hypodontia, delayed tooth eruption, morphological dental abnormalities, dental malocclusions, cleft lip/palate and ogival palate. Based on our clinical experience, Wolf-Hirschhorn syndrome does not represent an absolute contraindication for any type of dental procedure. The feasibility of dental treatment will depend mainly on the degree of epilepsy control and on the level of collaboration, this latter conditioned by the severity of the intellectual disability and communication difficulties.

The Impact of Face Masks on the Emotional Reading Abilities of Children-A Lesson From a Joint School-University Project.

Wearing face masks has become a usual practice in acute infection events inducing the problem of misinterpreting the emotions of others. Empirical evidence about face masks mainly relies on adult data, neglecting, for example, school kids who firmly are dependent on effective nonverbal communication. Here we offer insights from a joint school-university project. Data indicate that emotional reading of 9 to 10 years old pupils (N = 57) was similarly impaired as adults on an overall performance level, but that their selective performance on specific emotions was quite different. Kids showed extreme problems in reading the emotion disgust, strong effects on fear and sadness, and only mild effects on happiness, but also even better performances for emotional states anger and neutral when faces were masked. This project did gain not only relevant data about children's perception but also made clear how fruitful seriously conducted school projects can be to encourage the interest and commitment for Science, Technology, Engineering, and Mathematics (STEM)-relevant topics.

Corrigendum: Paracetamol vs. Ibuprofen in Preterm Infants With Hemodynamically Significant Patent Ductus Arteriosus: A Non-inferiority Randomized Clinical Trial Protocol.

[This corrects the article DOI: 10.3389/fped.2020.00372.].

Paracetamol vs. Ibuprofen in Preterm Infants With Hemodynamically Significant Patent Ductus Arteriosus: A Non-inferiority Randomized Clinical Trial Protocol.

Background: Currently, the first line treatment of persistent ductus arteriosus (PDA) is either indomethacin or ibuprofen. However, the potentially life-threatening side effects associated to their use have prompted physicians to look for alternative options. The incorporation of paracetamol as an alternative to ibuprofen in the management of PDA is still based on insufficient clinical evidence. Hence, more clinical trials are needed to establish a therapeutic role for paracetamol in the management of PDA that take into consideration short- and long-term safety and efficacy outcomes. Study Design: This is a non-inferiority, randomized, multicenter, double-blinded study to evaluate the efficacy, and safety of intravenous (IV) paracetamol vs. IV ibuprofen (standard treatment) for PDA in preterm patients with a gestational age ≤ 30 weeks. At baseline, patients will be randomized (1:1) to treatment with paracetamol or ibuprofen. The primary endpoint is closure of the ductus after the first treatment course. Secondary endpoints are related to effectiveness (need for a second treatment course, rescue treatment, reopening rate, time to definitive closure, need for surgical ligation), safety (early and long-term complications), pharmacokinetics, and pharmacodynamics, pharmacogenetics, pharmacoeconomics, and genotoxicity. Long-term follow-up to 24 months of corrected postnatal age will be performed using Bayley III neurodevelopmental scale. Trial Registration: ClinicalTrials.gov Identifier: NCT04037514. EudraCT: 2015-003177-14.

Internet of Robotic Things Intelligent Connectivity and Platforms.

The Internet of Things (IoT) and Industrial IoT (IIoT) have developed rapidly in the past few years, as both the Internet and "things" have evolved significantly. "Things" now range from simple Radio Frequency Identification (RFID) devices to smart wireless sensors, intelligent wireless sensors and actuators, robotic things, and autonomous vehicles operating in consumer, business, and industrial environments. The emergence of "intelligent things" (static or mobile) in collaborative autonomous fleets requires new architectures, connectivity paradigms, trustworthiness frameworks, and platforms for the integration of applications across different business and industrial domains. These new applications accelerate the development of autonomous system design paradigms and the proliferation of the Internet of Robotic Things (IoRT). In IoRT, collaborative robotic things can communicate with other things, learn autonomously, interact safely with the environment, humans and other things, and gain qualities like self-maintenance, self-awareness, self-healing, and fail-operational behavior. IoRT applications can make use of the individual, collaborative, and collective intelligence of robotic things, as well as information from the infrastructure and operating context to plan, implement and accomplish tasks under different environmental conditions and uncertainties. The continuous, real-time interaction with the environment makes perception, location, communication, cognition, computation, connectivity, propulsion, and integration of federated IoRT and digital platforms important components of new-generation IoRT applications. This paper reviews the taxonomy of the IoRT, emphasizing the IoRT intelligent connectivity, architectures, interoperability, and trustworthiness framework, and surveys the technologies that enable the application of the IoRT across different domains to perform missions more efficiently, productively, and completely. The aim is to provide a novel perspective on the IoRT that involves communication among robotic things and humans and highlights the convergence of several technologies and interactions between different taxonomies used in the literature.

PHOTODYNAMIC THERAPY WITH VERTEPORFIN PLUS INTRAVITREAL BEVACIZUMAB FOR CIRCUMSCRIBED CHOROIDAL HEMANGIOMA: 4 YEARS OF FOLLOW-UP.

PURPOSE: To report the anatomical and functional response of combined photodynamic therapy and intravitreal injection of bevacizumab in a patient with symptomatic circumscribed choroidal hemangioma. METHODS: The patient received a single-session full-fluence photodynamic therapy immediately followed by an intravitreal injection of bevacizumab (1.25 mg/0.05 mL). RESULTS: One week after combined therapy, an improvement of best-corrected visual acuity from count fingers to 20/60 and a significant decrease in subretinal fluid were noted. One month later, we observed decreased leakage on fluorescein angiography in all phases of the study. Three months after treatment, the best-corrected visual acuity improved to 20/25 and spectral domain optical coherence tomography scans showed return to normal foveal architecture with no subretinal fluid and completely flat tumor. These findings were maintained during 4 years of follow-up. CONCLUSION: Combination therapy was associated with a rapid and persistent resolution of subretinal fluid, improvement of best-corrected visual acuity, and visual stability at 4 years of follow-up.

International meeting on Wolf-Hirschhorn syndrome: Update on the nosology and new insights on the pathogenic mechanisms for seizures and growth delay.

"An International Meeting on Wolf-Hirschhorn Syndrome (WHS)" was held at The University Hospital La Paz in Madrid, Spain (October 13-14, 2017). One hundred and twenty-five people, including physicians, scientists and affected families, attended the meeting. Parent and patient advocates from the Spanish Association of WHS opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes. These proceedings will review the major points of discussion.

EAGLE-A Scalable Query Processing Engine for Linked Sensor Data.

Recently, many approaches have been proposed to manage sensor data using semantic web technologies for effective heterogeneous data integration. However, our empirical observations revealed that these solutions primarily focused on semantic relationships and unfortunately paid less attention to spatio-temporal correlations. Most semantic approaches do not have spatio-temporal support. Some of them have attempted to provide full spatio-temporal support, but have poor performance for complex spatio-temporal aggregate queries. In addition, while the volume of sensor data is rapidly growing, the challenge of querying and managing the massive volumes of data generated by sensing devices still remains unsolved. In this article, we introduce EAGLE, a spatio-temporal query engine for querying sensor data based on the linked data model. The ultimate goal of EAGLE is to provide an elastic and scalable system which allows fast searching and analysis with respect to the relationships of space, time and semantics in sensor data. We also extend SPARQL with a set of new query operators in order to support spatio-temporal computing in the linked sensor data context.

Preoperative Bevacizumab for Tractional Retinal Detachment in Proliferative Diabetic Retinopathy: A Prospective Randomized Clinical Trial.

PURPOSE: To assess the effectiveness and safety of an intravitreal injection of 1.25 mg bevacizumab (IVB) as a preoperative adjunct to small-gauge pars plana vitrectomy (PPV) compared with PPV alone in eyes with tractional retinal detachment secondary to proliferative diabetic retinopathy. METHODS: This prospective, double-masked, randomized, multicenter, active-controlled clinical trial enrolled 224 eyes of 224 patients between November 2013 and July 2015. All eyes underwent a baseline examination including best-corrected visual acuity, color photos, optical coherence tomography, and fluorescein angiography. Data were collected on intraoperative bleeding, total surgical time, early (<1 month) postoperative vitreous hemorrhage, and mean change in best-corrected visual acuity at 12 months. P < .05 was considered statistically significant. RESULTS: A total of 214 patients (214 eyes) were randomized in a 1:1 ratio to PPV plus IVB ([study group] 102 eyes) or PPV plus sham ([control] 112 eyes). Iatrogenic retinal breaks were noted intraoperatively in 35 eyes (34.3%) in the study group, and 66 eyes (58.9%) in the control group (P = .001). Grade 2 intraoperative bleeding was noted in 32 (31.3%) eyes in the study group and 58 (51.7 %) eyes in the control group (P = .001). Endodiathermy was necessary in 28 (27.4 %) eyes in the study group, compared with 75 (66.9%) eyes in the control group (P = .0001). Mean surgical time was 71.3 ± 32.1 minutes in the study group and 83.6 ± 38.7 minutes in the control group (P = .061). CONCLUSION: Preoperative IVB seems to reduce intraoperative bleeding, improving surgical field visualization, and reducing intraoperative and postoperative complications. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Anti-leishmanial effect of spiro dihydroquinoline-oxindoles on volume regulation decrease and sterol biosynthesis of Leishmania braziliensis.

Diverse spiro dihydroquinoline-oxindoles (JS series) were prepared using the BF3•OEt2-catalyzed imino Diels-Alder reaction between ketimine-isatin derivatives and trans-isoeugenol. Ten spiro-oxiindole derivatives were selected and evaluated at different stages of the life cycle of Leishmania braziliensis parasites, responsible for cutaneous leishmaniasis in South America. Among them, the 8'-ethyl-4'-(4-hydroxy-3-methoxyphenyl)-3'-methyl-3',4'-dihydro-1'H-spiro[indoline-3,2'-quinolin]-2-one called JS87 was able to inhibit the growth of promastigotes without affecting the mammalian cells viability, and to decrease the number of intracellular amastigotes of L. braziliensis. This spiro compound was found to act through the alteration of parasite internal regulation by disrupting the regulatory volume decrease (RVD), and to affect the sterol biosynthetic pathway at level of squalene epoxidase (SE) enzyme. These results revealed that the spiro annulation between quinoline and oxindole scaffolds enhances the anti-leishmanial activity, and could assist in the development of potent quinoline-oxindole hybrids against Leishmania braziliensis, the main etiological agent of cutaneous leishmaniasis in South America.

Yellow (577 nm) micropulse laser versus half-dose verteporfin photodynamic therapy in eyes with chronic central serous chorioretinopathy: results of the Pan-American Collaborative Retina Study (PACORES) Group.

PURPOSE: To compare the functional and anatomical outcomes of eyes with chronic central serous chorioretinopathy treated with yellow micropulse (MP) laser versus half-dose verteporfin photodynamic therapy (PDT). METHODS: This is a multicentre, retrospective comparative study of 92 eyes treated with yellow MP laser (duty cycle of 5%, zero spacing between spots, spot size varied from 100 to 200 µm, power varied from 320 to 660 mW, and the pulse burst duration was 200 ms) and 67 eyes treated with PDT (half-dose verteporfin (3 mg/m2) infused over 10 min), followed by laser activation for 83 s. Spot sizes varied from 400 to 2000 µm. RESULTS: In the MP group, at 12 months of follow-up, the mean best corrected visual acuity (BCVA) improved from the logarithm of the minimum angle of resolution (logMAR) of 0.41±0.27 at baseline to 0.21±0.26 (P<0.0001), 48.9% (45/92) of eyes had an improvement of ≥3 lines of BCVA from baseline, 48.9% (45/92) of eyes remained within 2 lines of baseline BCVA, and only 2.2% (2/92) of eyes lost ≥3 lines of BCVA from baseline. In the PDT group, at 12 months of follow-up, the mean BCVA changed from logMAR of 0.50±0.34 at baseline to 0.47±0.34 (P=0.89), 19% (13/67) of eyes had an improvement of ≥3 lines of BCVA from baseline, 73% (49/67) of eyes remained within 2 lines of baseline BCVA, and 7% (5/67) of eyes lost ≥3 lines of BCVA from baseline. There were no adverse events attributable to the yellow MP laser treatment. One eye in the PDT group developed choroidal neovascularisation, which was treated with three intravitreal bevacizumab injections. CONCLUSIONS: Both PDT and MP are effective in restoring the macular anatomy. In places where PDT is not available, yellow MP laser may be an adequate treatment alternative.

Intravitreal bevacizumab monotherapy in myopic choroidal neovascularisation: 5-year outcomes for the PAN-American Collaborative Retina Study Group.

PURPOSE: To report the long-term anatomical and visual outcomes of intravitreal bevacizumab (IVB) monotherapy in naive choroidal neovascularisation (CNV) caused by myopia. METHODS: Retrospective analysis of naive CNV secondary to myopia that underwent antivascular endothelial growth factor monotherapy was performed. Collected data included demographic details, clinical examination details including visual acuity at presentation and follow-up with imaging and treatment details. Main outcome measures were resolution of CNV activity at the last visit. Secondary outcomes included change in visual acuity, number of injections and adverse events. RESULTS: Thirty-three eyes of 31 subjects with a mean age of 51.48±16.4 years were included. The mean follow-up was 66.47 months. 27 eyes had type 2 CNV and the rest seven eyes had type 1 CNV. The mean number of IVB injections per eye was 4.9. Mean visual acuity at baseline reduced from 0.65±0.33 logMAR units (Snellen equivalent=20/89) to 0.73±0.50 logMAR units (20/107) at final follow-up (p=0.003). The mean central macular thickness decreased from 309.31±86 µm at baseline to 267.5±70.89 µm at the last visit (p=0.03). However, visual acuity was maintained (±1 line of baseline) in 13 eyes (39.4%), ≥2 line improvement in nine (27.3%) eyes and more than two lines worsening in 11 eyes (33.3%). Foveal atrophy was observed at baseline and last visit in 6 (12.5%) and 14 (29.1%), respectively (p=0.007). No systemic adverse events were observed. CONCLUSION: IVB monotherapy is safe and effective for long-term treatment of CNV secondary to myopia in real life.

Mechanism of Action of Miltefosine on Leishmania donovani Involves the Impairment of Acidocalcisome Function and the Activation of the Sphingosine-Dependent Plasma Membrane Ca2+ Channel.

Leishmania donovani is the causing agent of visceral leishmaniasis, a common infection that affects millions of people from the most underdeveloped countries. Miltefosine is the only oral drug to treat infections caused by L. donovani Nevertheless, its mechanism of action is not well understood. While miltefosine inhibits the synthesis of phosphatidylcholine and also affects the parasite mitochondrion, inhibiting the cytochrome c oxidase, it is to be expected that this potent drug also produces its effect through other targets. In this context, it has been reported that the disruption of the intracellular Ca2+ homeostasis represents an important object for the action of drugs in trypanosomatids. Recently, we have described a plasma membrane Ca2+ channel in Leishmania mexicana, which is similar to the L-type voltage-gated Ca2+ channel (VGCC) present in humans. Remarkably, the parasite Ca2+ channel is activated by sphingosine, while the L-type VGCC is not affected by this sphingolipid. In the present work we demonstrated that, similarly to sphingosine, miltefosine is able to activate the plasma membrane Ca2+ channel from L. donovani Interestingly, nifedipine, the classical antagonist of the human channel, was not able to fully block the parasite plasma membrane Ca2+ channel, indicating that the mechanism of interaction is not identical to that of sphingosine. In this work we also show that miltefosine is able to strongly affect the acidocalcisomes from L. donovani, inducing the rapid alkalinization of these important organelles. In conclusion, we demonstrate two new mechanisms of action of miltefosine in L. donovani, both related to disruption of parasite Ca2+ homeostasis.

Un-explained visual loss following silicone oil removal: results of the Pan American Collaborative Retina Study (PACORES) Group.

PURPOSE: To report the incidence and clinical features of patients that experienced un-explained visual loss following silicone oil (SO) removal. METHODS: Multicenter retrospective study of patients that underwent SO removal during 2000-2012. Visual loss of ≥2 lines was considered significant. RESULTS: A total of 324 eyes of 324 patients underwent SO removal during the study period. Forty two (13%) eyes suffered a significant visual loss following SO removal. Twenty three (7.1%) of these eyes lost vision secondary to known causes. In the remaining 19 (5.9%) eyes, the loss of vision was not explained by any other pathology. Eleven of these 19 patients (57.9%) were male. The mean age of this group was 49.2 ± 16.4 years. Eyes that had an un-explained visual loss had a mean IOP while the eye was filled with SO of 19.6 ± 6.9 mm Hg. The length of time that the eye was filled with SO was 14.8 ± 4.4 months. In comparison, eyes that did not experience visual loss had a mean IOP of 14 ± 7.3 mm Hg (p < 0.0002) and a mean tamponade duration of 9.3 ± 10.9 months (p < 0.0001). CONCLUSIONS: An un-explained visual loss after SO removal was observed in 5.9% of eyes. Factors associated with this phenomenon included a higher IOP and longer SO tamponade duration.