Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Search for Gamma-Ray Spectral Lines from Dark Matter Annihilation up to 100 TeV toward the Galactic Center with MAGIC.

Linelike features in TeV γ rays constitute a "smoking gun" for TeV-scale particle dark matter and new physics. Probing the Galactic Center region with ground-based Cherenkov telescopes enables the search for TeV spectral features in immediate association with a dense dark matter reservoir at a sensitivity out of reach for satellite γ-ray detectors, and direct detection and collider experiments. We report on 223 hours of observations of the Galactic Center region with the MAGIC stereoscopic telescope system reaching γ-ray energies up to 100 TeV. We improved the sensitivity to spectral lines at high energies using large-zenith-angle observations and a novel background modeling method within a maximum-likelihood analysis in the energy domain. No linelike spectral feature is found in our analysis. Therefore, we constrain the cross section for dark matter annihilation into two photons to ⟨σv⟩≲5×10^{-28} cm^{3} s^{-1} at 1 TeV and ⟨σv⟩≲1×10^{-25} cm^{3} s^{-1} at 100 TeV, achieving the best limits to date for a dark matter mass above 20 TeV and a cuspy dark matter profile at the Galactic Center. Finally, we use the derived limits for both cuspy and cored dark matter profiles to constrain supersymmetric wino models.

State of refractive surgery with Visian ICL posterior chamber phakic lens in Spain.

OBJECTIVES: To analyse the state of refractive surgery with Visian ICL phakic lens implantation in Spain, indicating the mean ranges of implanted powers, visual and refractive outcomes obtained and safety and efficacy indices. METHOD: This is a population-based, cross-sectional, descriptive, analytical, retrospective, multicentre study in which each co-author collected data from at least the last 10 patients (up to a maximum of 30) with Visian ICL phakic lens implantation. One eye from each subject was randomly selected for study inclusion, and the variables analysed were: age, gender, visual acuities with and without correction pre and post-surgery, preoperative and residualrefraction, keratometry, endothelial cellular density, anterior chamber depth from endothelium, central corneal pachymetry, intraocular pressure, white-white, implanted lens (power and size), expected and achieved spherical equivalent (SEQ) post-surgery at one month after surgery. RESULTS: A sample of 140 eyes was obtained from 140 patients with a mean age of 31.35 ± 7.28 years. Mean preoperative SEQ was -6.33 ± 3.69D, mean CDVA was 0.96 ± 0.16, ACD was 3.30 ± 0.29 mm, WTW 12.02 ± 0.40 mm, CCT 535.03 ± 37.68 µm, ECD 2684.37 ± 313.74 cels/mm2 and IOP 14.84 ± 2.59 mmHg. 66.4% of the implanted lenses were spherical ICLs and 33.6% toric, with a mean power of -7.81 ± 4.09D and a mean cylinder of 2.27 ± 1.23D. 5.7% of the implanted lenses were hypermetropic. The mean SEQ target selected was +0.04 ± 0.27D. 48.92% of the implanted lenses were of size 13.2 mm, with the remaining 36.69, 10.79 and 3.60% being of sizes 12.6, 12.1 and 13.7 mm, respectively. At one month after surgery a residual SEQ of -0.01 ± 0.31D was obtained. The efficacy and safety indices were 1.06 ± 0.18 and 1.10 ± 0.19, respectively. The mean central vault was 508.80 ± 201.04 µm. The accuracy between the calculated SEQ and the obtained SEQ was 99.3% for spherical lenses and 88.2% for Cyl correction. The mean ECD at 1 month after surgery was 2805.53±273.30céls/mm2, which was a difference from preoperative of 0.11% (p = 0.922), similarly, the mean IOP was 13.98 ± 2.57 mmHg, which was a difference of -0.92 ± 2.80 mmHg. CONCLUSIONS: ICL phakic lens surgery is an effective, safe and predictable procedure. There were no significant changes in endothelial cell count or intraocular pressure measurement one month after surgery.

Position estimation using neural networks in semi-monolithic PET detectors.

Objective. The goal of this work is to experimentally compare the 3D spatial and energy resolution of a semi-monolithic detector suitable for total-body positron emission tomography (TB-PET) scanners using different surface crystal treatments and silicon photomultiplier (SiPM) models.Approach. An array of 1 × 8 lutetium yttrium oxyorthosilicate (LYSO) slabs of 25.8 × 3.1 × 20 mm3separated with Enhanced Specular Reflector (ESR) was coupled to an array of 8 × 8 SiPMs. Three different treatments for the crystal were evaluated: ESR + RR + B,with lateral faces black (B) painted and a retroreflector (RR) layer added to the top face; ESR +RR, with lateral faces covered with ESR and a RR layer on the top face and; All ESR, with lateral and top sides with ESR. Additionally, two SiPM array models from Hamamatsu Photonics belonging to the series S13361-3050AE-08 (S13) and S14161-3050AS-08 (S14) have been compared. Coincidence data was experimentally acquired using a22Na point source, a pinhole collimator, a reference detector and moving the detector under study in 1 mm steps in thex- andDOI- directions. The spatial performance was evaluated by implementing a neural network (NN) technique for the impact position estimation in thex- (monolithic) andDOIdirections.Results. Energy resolution values of 16 ± 1%, 11 ± 1%, 16 ± 1%, 15 ± 1%, and 13 ± 1% were obtained for theS13-ESR + B + RR,S13-AllESR,S14-ESR + B + RR,S14-ESR + RR,andS14-AllESR, respectively. Regarding positioning accuracy, mean average error of 1.1 ± 0.5, 1.3 ± 0.5 and 1.3 ± 0.5 were estimated for thex- direction and 1.7 ± 0.8, 2.0 ± 0.9 and 2.2 ± 1.0 for theDOI- direction, for the ESR + B + RR, ESR + RR and All ESR cases, respectively, regardless of the SiPM model.Significance. Overall, the obtained results show that the proposed semi-monolithic detectors are good candidates for building TB-PET scanners.

Intense pulsed light combined with meibomian gland expression for chalazion management.

OBJECTIVE: To investigate the efficacy and safety of an intense pulsed light (IPL) combined IPL treatment protocol for meibomian gland dysfunction (MGD)/dry eye disease (DED) with IPL applied directly to the eyelids, associated with meibomian gland (MG) expression for the treatment of chalazion. MATERIAL AND METHODS: Retrospective case series study. Patients presenting with chalazion received a combined IPL therapy treatment consisting of using the usual IPL protocol for DGM/EOS using a fluence according to skin type according to Fitzpatrick, followed by a second phase (in the same session) of IPL application directly on the eyelids of both eyes using a fluence of 10J/cm2. All patients then received GM expression, eyelid hygiene, topical antibiotic and topical ocular anti-inflammatory medication. Adverse effects related to this protocol were assessed at each IPL session. RESULTS: Twenty-six chalazions from nineteen patients (24 eyes) with a mean age of 49.89±20.43 years were included. An average of 2.07±0.97 IPL sessions were required for chalazion resolution. The combined treatment of IPL protocol and GM expression showed 96.15% efficacy and no adverse effects were observed. CONCLUSIONS: Combined IPL treatment for MGD/DED with IPL applied directly onto the eyelids and MGX could be effective and safe for the management of chalazions.

Corneal Stroma Regeneration: New Approach for the Treatment of Cornea Disease.

Corneal grafting is one of the most common forms of human tissue transplantation. The corneal stroma is responsible for many characteristics of the cornea. For these reasons, an important volume of research has been made to replicate the corneal stroma in the laboratory to find an alternative to classical corneal transplantation techniques.There is an increasing interest today in cell therapy of the corneal stroma using induced pluripotent stem cells or mesenchymal stem cells since these cells have shown to be capable of producing new collagen within the host stroma and even to improve its transparency.The first clinical experiment on corneal stroma regeneration in advanced keratoconus cases has been reported and included. Fourteen patients were randomized and enrolled into 3 experimental groups: (1) patients underwent implantation of autologous adipose-derived adult stem cells alone, (2) patients received decellularized donor corneal stroma laminas, and (3) patients received implantation of recellularized donor laminas with adipose-derived adult stem cells. Clinical improvement was detected with all cases in their visual, pachymetric, and topographic parameters of the operated corneas.Other recent studies have used allogenic SMILE implantation lenticule corneal inlays, showing also an improvement in different visual, topographic, and keratometric parameters.In the present report, we try to summarize the available preclinical and clinical evidence about the emerging topic of corneal stroma regeneration.

MACACO II test-beam with high energy photons.

The IRIS group at IFIC Valencia is developing a three-layer Compton camera for treatment monitoring in proton therapy. The system is composed of three detector planes, each made of a [Formula: see text] monolithic crystal coupled to a SiPM array. Having obtained successful results with the first prototype (MACACO) that demonstrated the feasibility of the proposed technology, a second prototype (MACACO II) with improved performance has been developed, and is the subject of this work. The new system has an enhanced detector energy resolution which translates into a higher spatial resolution of the telescope. The image reconstruction method has also been improved with an accurate model of the sensitivity matrix. The device has been tested with high energy photons at the National Accelerator Centre (CNA, Seville). The tests involved a proton beam of 18 MeV impinging on a graphite target, to produce 4.4 MeV photons. Data were taken at different system positions of the telescope with the first detector at 65 and 160 mm from the target, and at different beam intensities. The measurements allowed successful reconstruction of the photon emission distribution at two target positions separated by 5 mm in different telescope configurations. This result was obtained both with data recorded in the first and second telescope planes (two interaction events) and, for the first time in beam experiments, with data recorded in the three planes (three interaction events).

Intraoperative transesophageal echocardiography in cardiovascular surgery. Consensus document from the Spanish Society of Anesthesia and Critical Care (SEDAR) and the Spanish Society of Endovascular and Cardiovascular Surgery (SECCE). / Ecocardiografía transesofágica intraoperatoria en cirugía cardiovascular. Documento de consenso de la Sociedad Española de Anestesiología y Reanimación (SEDAR) y Sociedad Española de Cirugía Cardiovascular y Endovascular (SECCE).

Transesophageal echocardiography is a semi-invasive technique that allows an evaluation of cardiac morphology and function in real time and it is a quality standard in cardiovascular surgery. It has become a fundamental tool for both monitoring and diagnosis in the intraoperative period that allows decide the correct surgical planning and pharmacological management. The goal of this document is to answer the questions of when and how the perioperative TEE should be performed in cardiovascular surgery, what are their applications in the intraoperative, who should perform it and how the information should be transmitted. The authors made a systematic review of international guidelines, review articles and clinical trials to answer by consensus to these questions.

Bounds on Lorentz Invariance Violation from MAGIC Observation of GRB 190114C.

On January 14, 2019, the Major Atmospheric Gamma Imaging Cherenkov telescopes detected GRB 190114C above 0.2 TeV, recording the most energetic photons ever observed from a gamma-ray burst. We use this unique observation to probe an energy dependence of the speed of light in vacuo for photons as predicted by several quantum gravity models. Based on a set of assumptions on the possible intrinsic spectral and temporal evolution, we obtain competitive lower limits on the quadratic leading order of speed of light modification.

Recommendations for eye care during the alarm state by the coronavirus disease pandemic COVID-19. / Recomendaciones para la atención oftalmológica durante el estado de alarma por la pandemia de enfermedad por coronavirus COVID-19.

OBJECTIVE: Minimize exposure to the SARS-CoV-2, reduce the chances of cross-transmission between patients and healthcare personnel, and prevent the development of postoperative complications from the management of patients with eye diseases during the 2019 coronavirus disease pandemic (COVID-19). METHODS: COVID-19 literature review and consensus establishment between different Spanish ophthalmology societies in order to provide guidelines and recommendations of maximum resources primarily conditioned by the state of alert, confinement and social distancing that occurs in Spain since March 16, 2020. RESULTS: The recommendations will promote the adoption of action and protection measures for eye care in outpatient clinics, surgical areas and hospitalization, for unconfirmed (asymptomatic and symptomatic) and confirmed COVID-19 patients. Measures must be adapted to the circumstances and availability of personal protective equipment in each of the centers and Autonomous Communities, which will be updated according to the pandemic phases and the measures adopted by the Spanish Government. CONCLUSIONS: During the COVID-19 pandemic, attention to the potential health risks to the population caused by coronavirus should prevail over the possible progression of the common eye diseases. Ophthalmologists and other eye care professionals must assume a possible progression of these diseases due to the impossibility of adequate patient follow-up.

Image reconstruction for a multi-layer Compton telescope: an analytical model for three interaction events.

Compton Cameras are electronically collimated photon imagers suitable for sub-MeV to few MeV gamma-ray detection. Such features are desirable to enable in vivo range verification in hadron therapy, through the detection of secondary Prompt Gammas. A major concern with this technique is the poor image quality obtained when the incoming gamma-ray energy is unknown. Compton Cameras with more than two detector planes (multi-layer Compton Cameras) have been proposed as a solution, given that these devices incorporate more signal sequences of interactions to the conventional two interaction events. In particular, three interaction events convey more spectral information as they allow inferring directly the incident gamma-ray energy. A three-layer Compton Telescope based on continuous Lanthanum (III) Bromide crystals coupled to Silicon Photomultipliers is being developed at the IRIS group of IFIC-Valencia. In a previous work we proposed a spectral reconstruction algorithm for two interaction events based on an analytical model for the formation of the signal. To fully exploit the capabilities of our prototype, we present here an extension of the model for three interaction events. Analytical expressions of the sensitivity and the System Matrix are derived and validated against Monte Carlo simulations. Implemented in a List Mode Maximum Likelihood Expectation Maximization algorithm, the proposed model allows us to obtain four-dimensional (energy and position) images by using exclusively three interaction events. We are able to recover the correct spectrum and spatial distribution of gamma-ray sources when ideal data are employed. However, the uncertainties associated to experimental measurements result in a degradation when real data from complex structures are employed. Incorrect estimation of the incident gamma-ray interaction positions, and missing deposited energy associated with escaping secondaries, have been identified as the causes of such degradation by means of a detailed Monte Carlo study. As expected, our current experimental resolution and efficiency to three interaction events prevents us from correctly recovering complex structures of radioactive sources. However, given the better spectral information conveyed by three interaction events, we expect an improvement of the image quality of conventional Compton imaging when including such events. In this regard, future development includes the incorporation of the model assessed in this work to the two interaction events model in order to allow using simultaneously two and three interaction events in the image reconstruction.

Macular ganglion cell complex thinning in children with visual field defects due to central nervous system pathology.

PURPOSE: To study the relationship between macular ganglion cell complex (GCC) thickness and visual field defects (VFD) caused by central nervous system (CNS) lesions in children and evaluate the possibility of predicting VFD according to GCC maps. METHODS: The GCC maps of a group of children with VFD due to CNS lesions with respect of the vertical meridian in at least one eye (study group), as well as of children with other neuro-ophthalmological problems and healthy children were presented to two masked evaluators, who were asked to predict the patients' VFD on the basis of GCC damage: the evaluators classified VFD as normal, hemianopia (homonymous or heteronymous) or diffuse. RESULTS: Seventeen patients were included in the study group, with a median age of 12 years. Fifteen had brain tumours and two epilepsy. The mean MD of the affected hemifields was -26.00 dB (SD 7.89 dB) versus -5.51 dB (SD 3.52 dB) for the nonaffected hemifields, p < 0.001. The mean GCC thickness was of 56.04 µm (SD 11.95 µm) in the affected hemiretinas versus 74.31 µm (SD 10.64 µm) for the non-affected, p < 0.001. Kappa coefficients between VFD and those estimated by the evaluators were 0.705 and 0.658 (p < 0.001) for evaluators 1 and 2. CONCLUSIONS: GCC thickness can reflect damage to the visual pathway and GCC maps may be useful to identify chiasmal and retrochiasmal lesions, since GCC atrophy in most of these cases respects the vertical meridian. GCC maps might be used as a surrogate marker for visual damage in patients unable to perform perimetry.

Assessment of the Association between In Vivo Corneal Morphogeometrical Changes and Keratoconus Eyes with Severe Visual Limitation.

Assessing changes suffered by the cornea as keratoconus progresses has proven to be vital for this disease diagnosis and treatment. This study determines the corneal biometric profile in eyes considered as affected by keratoconus (KC) showing severe visual limitation, by means of in vivo 3D modelling techniques. This observational case series study evaluated new objective indices in 50 healthy and 30 KC corneas, following a validated protocol created by our research group, which has been previously used for diagnosis and characterization of KC in asymptomatic (preclinical) and mild visually impaired eyes. Results show a statistically significant reduction of corneal volume and an increase of total corneal area in the severe KC group, being anterior and posterior corneal surfaces minimum thickness points the best correlated parameters, although with no discrimination between groups. Receiving operator curves were used to determine sensitivity and specificity of selected indices, being anterior and posterior apex deviations the ones which reached the highest area under the curve, both with very high sensitivity (96.7% and 90%, respectively) and specificity (94.0% and 99.9%, respectively). The results suggest that once severe visual loss appears, anterior corneal topography should be considered for a more accurate diagnosis of clinical KC, being anterior apex deviation the key metric discriminant. This study can be a useful tool for KC classification, helping doctors in diagnosing severe cases of the disease, and can help to characterize corneal changes that appear when severe KC is developed and how they relate with vision deterioration.

Perforation of the left ventricle wall due to the insertion of a pulmonary artery catheter. A case report. / Perforación de la pared del ventrículo izquierdo por catéter de arteria pulmonar Swan-Ganz. A propósito de un caso.

Despite the widespread and frequent use in our setting of pulmonary artery catheters for haemodynamic management in critically ill patients, particularly after heart surgery, some experts continue to question the need for these devices. Clinicians need to weigh up the risks and benefits of pulmonary artery catheters placement and bear in mind the potential complications which, though rare, can be potentially fatal. We present a pulmonary artery catheters-related complication not hitherto described in the literature, involving perforation of the interventricular septum and left ventricular free wall caused by a kink in the pulmonary artery catheters that was not suspected, and only diagnosed by direct vision of the heart after pericardial opening. In the interest of patient safety, we must consider the impact of adverse events; improving our situational awareness and our understanding of the mechanisms behind such events can help reduce the likelihood of repetitions in the future.

Recurrent non-functioning pituitary adenomas: a review on the new pathological classification, management guidelines and treatment options.

At least 50% of surgically resected non-functioning pituitary adenomas (NFPA) recur. Either early or late adjuvant radiotherapy is highly efficacious in controlling recurrent NFPA but associates potentially burdensome complications like hypopituitarism, vascular complications or secondary neoplasm. Reoperation is indicated in bulky tumor rests compressing the optic pathway. To date, no standardized medical therapy is available for recurrent NFPA although cabergoline and temozolomide show promising results. Guidelines on the management of recurrent NFPAs are now available. The new 2017 WHO pituitary tumor classification, based on immunohistochemistry and transcription factor assessment, identifies a group of aggressive NFPA variants that may benefit from earlier adjuvant therapy. Nevertheless, NFPA patients exhibit a reduced overall life expectancy largely due to hypopituitarism and treatment-related morbidity. The management of recurrent NFPA benefits from a multidisciplinary teamwork of surgeons, endocrinologists, radiation oncologists, ophthalmologists, pathologists and neuro-radiologists in order to provide individualized therapy and anticipate deterioration.