[Home CPAP Remote Monitoring as a System to Control Adaptation and Titration in Obstructive Sleep Apnoea and its Impact on the Management of this Pathology (T-CPAP Project)]. / Impacto de la telemonitorización como sistema para una adecuada titulación y adaptación de la CPAP domiciliaria en la apnea obstructiva del sueño (proyecto T-CPAP).

Introduction: Continuous Positive Airway Pressure (CPAP) constitutes the most effective treatment for Obstructive Sleep Apnea (OSA). Automatic titration systems (ATS) are predominantly used to achieve adaptation to the equipment. Home CPAP devices allow telemonitoring (TM) of the same parameters as those provided by ATS but with access to continuous usage data. Under this premise, we conducted a study on the potential validity of TM for home CPAP devices as a titration system, its direct impact on proper adaptation (AD) to the equipment, and secondarily on the healthcare resources employed to achieve it. Material and methods: An observational study involving 318 patients with OSA who were titrated using TM to achieve AD to CPAP. Patients with OSA were consecutively recruited and evaluated at 1, 3, and 6 months after initiating treatment. Results were compared with a historical group of 307 patients with OSA who achieved AD to CPAP using ATS. Additionally, we assessed the impact on required healthcare resources. Results: Patients with OSA who initiated CPAP treatment with TM over the first six months showed a similar AD rate compared to the historical group titrated using ATS, with lower resource usage in the TM group. Conclusion: Data provided by TM of home CPAP devices allow for titration and achieving similar AD as with ATS in non-complex patients.

Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

Congenital stromal corneal dystrophy in a Spanish family: Clinical, genetic and histological analysis.

PURPOSE: To present the clinical, genetic, and histopathological features of the ninth family affected by congenital stromal corneal dystrophy (CSCD) to date. METHODS: Twelve cases of a Spanish family affected by CSCD were analyzed regarding history, visual acuity (VA, decimal scale), an ophthalmologic exam and specular microscopy. Five eyes were treated by deep anterior lamellar keratoplasty (DALK), and thirteen eyes by penetrating keratoplasty (PK). In the two last generations, a genetic study was performed. RESULTS: Most of the patients affected were born with opaque corneas except for three, whose corneas were clear at birth. Biomicroscopy showed a whitish diffuse stromal opacity with an unaltered epithelium, causing poor VA (from hand motions to 0.4). Patients treated with PK presented mean postoperative VA of 0.19±0.20 over a follow-up time of 235.3±101.4months with 38% recurrences. Patients who underwent DALK experienced VA improvement to 0.17±0.11 over a follow-up time of 10.8±2.6months without signs of recurrence. In the latter, the big bubble technique was not achieved, so a manual technique was performed. The genetic study showed heterozygosis for a 1-bp deletion at nucleotide 962 in exon 8 of the decorin gene. CONCLUSIONS: CSCD is a rare entity, which should be treated by DALK whenever possible, obtaining better results than PK. Close monitoring of children of affected individuals is important, because CSCD can progress during the early years of life.

Advancing ocular safety research: A comprehensive examination of benzocaine acute exposure without animal testing.

Benzocaine is a widely employed local anaesthetic; however, there is a notable dearth of preclinical and clinical evidence regarding its safety in ophthalmological products. To address this, a comprehensive strategy incorporating in silico and in vitro methodologies was proposed for assessing benzocaine's ocular toxicity without animal testing. To collect the in silico evidence, the QSAR Toolbox (v4.5) was used. A single exposure to two benzocaine concentrations (2% and 20%) was evaluated by in vitro methods. Hen's Egg Chorioallantoic Membrane Test (HET-CAM) was performed to evaluate the effects on the conjunctiva. To study corneal integrity, Short Time Exposure test (STE) and Bovine Corneal Opacity and Permeability (BCOP) assay, followed by histopathological analysis, were carried out. Results from both in silico and in vitro methodologies categorize benzocaine as non-irritating. The histopathological analysis further affirms the safety of using benzocaine in eye drops, as no alterations were observed in evaluated corneal strata. This research proposes a useful combined strategy to provide evidence on the safety of local anaesthetics and particularly show that 2% and 20% benzocaine solutions do not induce eye irritation or corneal damage, supporting the potential use of benzocaine in the development of ophthalmic anesthetic products.

Cadaveric study of the ultrasound-guided erector spinae plane block over the transverse process of the twelfth thoracic vertebra in dogs: Transversal vs longitudinal approach.

This study describes a transversal (TV) ultrasound-guided erector spinae plane (ESP) block technique over the transverse process of T12. And evaluates the distribution of the dye and affected nerves branches compared to a longitudinal (LNG) approach over the transverse process of T12 in canine cadavers. Secondly, it also compares de anatomy and dimensions of the transverse processes of T12 with T9 and T5. For this double-masked, cadaveric experimental study, 12 adult Beagle cadavers were injected with 0.6 mL/kg of dye/contrast. Spread was evaluated by computed tomography (CT) and dissection. Mean bodyweight was 9.76 (±0.59) kg. The TV and LNG approaches stained a median (range) of four (2-6) and three (1-6) medial branches of the dorsal rami of the spinal nerves, three (2-6) and three (2-5) lateral branches, and one (0-3) and one (0-4) ventral branches, respectively. Dye was detected in the epidural space in 55.6% and 66.7% of cases for the TV and LNG approaches, respectively (P=0.63). And in the ventral paravertebral compartment in 22.2% and lymphatics in 88.8% in both approaches. There were no statistical differences for the spread. The dorsolateral edge of the transverse process (TP) was not visible with CT at T12. The mean (±SD) length of the TP was significantly shorter at T12 [3.34 (±0.22)] mm, compared to T9 [6.08 (±0.47)] mm and T5 [5.93 (±0.62)] mm (P <0.001). This study showed similar distribution whether using a TV or LNG approach and differences in the anatomy and length of the T12 TP.

Evaluación de la intervención de fisioterapia en los pacientes con sarcopenia y fractura de cadera: una revisión sistemática / Evaluation of physiotherapy intervention in patients with sarcopenia and hip fracture: A systematic review

Introducción La sarcopenia en los pacientes con fractura de cadera es cada vez más habitual en la población envejecida, aumentando el riesgo de hospitalización, dependencia y mortalidad. Objetivos Valorar el tratamiento de fisioterapia más efectivo en los pacientes con sarcopenia y fractura de cadera a través de la revisión de evidencia sistemática. Métodos Se realizó una búsqueda entre febrero y mayo de 2022 en 8 bases de datos electrónicas (Pubmed, Scopus, PEDro, Web of Science, Cochrane, Google Scholar y Springer Link), con el fin de extraer ensayos clínicos publicados en los últimos 12 años en español e inglés. Resultados Se seleccionaron 3 ensayos clínicos que cumplían los criterios de inclusión. En todos ellos las intervenciones de fisioterapia incluían ejercicio aeróbico, de fuerza, de alta intensidad, de movilizaciones y combinados. La calidad metodológica se evaluó con la escala PEDro (puntuación media entre 6 y 10). Uno de los estudios no encuentra diferencias entre el tratamiento estándar y el grupo que recibe además entrenamiento progresivo de fuerza muscular. Otro constata una mejora a corto plazo en el grupo que recibe además del tratamiento convencional entrenamiento en cinta rodante con soporte del peso corporal durante el ejercicio con seguimiento a los 3 y 6 meses. El estudio que suplementa con aminoácidos esenciales es el único que constata una mejoría en los pacientes con sarcopenia. Conclusión Los pacientes con sarcopenia y fractura de cadera, pueden tener una mejor evolución si combinan ejercicios de fisioterapia con un protocolo nutricional. Son necesarias más investigaciones metodológicamente rigurosas sobre este tema para poder ampliar la evidencia. (AU)

Introduction Sarcopenia in patients with hip fracture is increasingly common in the elderly population, increasing the risk of hospitalization, dependency, and mortality. Objectives To assess the most effective physiotherapy treatment in patients with sarcopenia and hip fracture through systematic evidence review. Methods Electronic databases were searched from February to May 2022 using Pubmed, Scopus, PEDro, Web of Science, Cochrane, Google Scholar, and Springer Link in order to extract randomized clinical trials published in full text both English and Spanish for the last 12 years. Results Three clinical trials that met the inclusion criteria were selected. In all of them, the physiotherapy interventions included aerobic, strength, high intensity, mobilization, and combined exercises. Methodological quality was assessed using the PEDro scale (average score between 6 and 10). One of the studies found no differences between the standard treatment and the group that also received progressive muscle strength training. Another found a short-term improvement in the group that received, in addition to conventional treatment, treadmill training with body weight support during exercise with follow-up that was not maintained at three and six months. The study that supplements with essential amino acids is the only one that confirms an improvement in patients with sarcopenia. Conclusion Patients with sarcopenia and hip fracture may have a better evolution if they combine physiotherapy exercises with a nutritional protocol. More methodologically rigorous research on this topic is needed to expand the evidence. (AU)

Evaluación de la intervención de fisioterapia en los pacientes con sarcopenia y fractura de cadera: una revisión sistemática / Evaluation of physiotherapy intervention in patients with sarcopenia and hip fracture: A systematic review

Introducción La sarcopenia en los pacientes con fractura de cadera es cada vez más habitual en la población envejecida, aumentando el riesgo de hospitalización, dependencia y mortalidad. Objetivos Valorar el tratamiento de fisioterapia más efectivo en los pacientes con sarcopenia y fractura de cadera a través de la revisión de evidencia sistemática. Métodos Se realizó una búsqueda entre febrero y mayo de 2022 en 8 bases de datos electrónicas (Pubmed, Scopus, PEDro, Web of Science, Cochrane, Google Scholar y Springer Link), con el fin de extraer ensayos clínicos publicados en los últimos 12 años en español e inglés. Resultados Se seleccionaron 3 ensayos clínicos que cumplían los criterios de inclusión. En todos ellos las intervenciones de fisioterapia incluían ejercicio aeróbico, de fuerza, de alta intensidad, de movilizaciones y combinados. La calidad metodológica se evaluó con la escala PEDro (puntuación media entre 6 y 10). Uno de los estudios no encuentra diferencias entre el tratamiento estándar y el grupo que recibe además entrenamiento progresivo de fuerza muscular. Otro constata una mejora a corto plazo en el grupo que recibe además del tratamiento convencional entrenamiento en cinta rodante con soporte del peso corporal durante el ejercicio con seguimiento a los 3 y 6 meses. El estudio que suplementa con aminoácidos esenciales es el único que constata una mejoría en los pacientes con sarcopenia. Conclusión Los pacientes con sarcopenia y fractura de cadera, pueden tener una mejor evolución si combinan ejercicios de fisioterapia con un protocolo nutricional. Son necesarias más investigaciones metodológicamente rigurosas sobre este tema para poder ampliar la evidencia. (AU)

Introduction Sarcopenia in patients with hip fracture is increasingly common in the elderly population, increasing the risk of hospitalization, dependency, and mortality. Objectives To assess the most effective physiotherapy treatment in patients with sarcopenia and hip fracture through systematic evidence review. Methods Electronic databases were searched from February to May 2022 using Pubmed, Scopus, PEDro, Web of Science, Cochrane, Google Scholar, and Springer Link in order to extract randomized clinical trials published in full text both English and Spanish for the last 12 years. Results Three clinical trials that met the inclusion criteria were selected. In all of them, the physiotherapy interventions included aerobic, strength, high intensity, mobilization, and combined exercises. Methodological quality was assessed using the PEDro scale (average score between 6 and 10). One of the studies found no differences between the standard treatment and the group that also received progressive muscle strength training. Another found a short-term improvement in the group that received, in addition to conventional treatment, treadmill training with body weight support during exercise with follow-up that was not maintained at three and six months. The study that supplements with essential amino acids is the only one that confirms an improvement in patients with sarcopenia. Conclusion Patients with sarcopenia and hip fracture may have a better evolution if they combine physiotherapy exercises with a nutritional protocol. More methodologically rigorous research on this topic is needed to expand the evidence. (AU)

Assessment of nitrification process in a sequencing batch reactor: Modelling and genomic approach.

Nitrification of ammoniacal nitrogen (N-NH4+) to nitrate (N-NO3-) was investigated in a lab-scale sequencing batch reactor (SBR) to evaluate its efficiency. During the nitrification process the removal of N-NH4+ reached 96%, resulting in 73% formation of N-NO3-. A lineal correlation (r2 = 0.9978) was obtained between the concentration of volatile suspended solids (VSS) and the maximal N-NO3- concentration at the end of each batch cycle under stationary state. The bacterial taxons in the initial inoculum were identified, revealing a complex diverse community mainly in the two major bacterial phyla Proteobacteria and Actinobacteria. The FAPROTAX algorithm predicted the presence in the inoculum of taxa involved in relevant processes of the nitrogen metabolism, highlighting the bacterial genera Nitrospira and Nitrosomonas that are both involved in the nitrification process. A kinetic model was formulated for predicting and validating the transformation of N-NH4+, N-NO2- and N-NO3- and the removal of organic and inorganic carbon (TOC and IC, respectively). The results showed how the increase in biomass concentration slowed down the transformation to oxidised forms of nitrogen and increased denitrification in the settling and filling stages under free aeration conditions.

Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

Efficacy and Safety outcomes of a novel model to assess new medical retina referrals in a high-volume medical retina virtual clinic.

BACKGROUND: Ophthalmology outpatient attendances have significantly increased recently with rising pressure from backlogs arising from the pandemic. Medical retina digital surveillance clinics for stable follow-up appointments are well established. We present a model for assessing new referrals and evaluating clinical outcomes and long-term sustainability in a complex high-volume medical retina service. METHODS: Suitable routine new patient referrals were identified from electronic referrals and referred to this new pathway. Structured history, visual acuities, and intraocular pressures were recorded, and widefield colour fundus and optical coherence tomography imaging were performed at a imaging hub for asynchronous consultant-led review. RESULTS: 1458 patients were invited to attend over four months, with a 13.2% did-not-attend (DNA) rate. Common diagnoses included stable diabetic retinopathy (19.9%), early age-related macular degeneration (6.7%), central serous retinopathy (8.8%), and retinal vein occlusion (6.3%). 7 patients (0.05%) required urgent same-day review. 61 (5.0%) required urgent face-to-face (F2F) assessment within two weeks. A total of 727 (59.0%) were either discharged or remained in the virtual pathway following their first visit. CONCLUSION: This study encourages the use of a digital model that efficiently assesses suitable newly referred medical retina patients in both complex and local eye unit settings. This decreased the need for F2F clinics and resources. Further patient satisfaction surveys for digital services are currently being evaluated to guide long-term sustainability of this model.

Loss of function mutations at the tomato SSI2 locus impair plant growth and development by altering the fatty acid desaturation pathway.

The stearoyl-ACP desaturase (SACPD) is a key enzyme in the regulation of saturated to unsaturated fatty acid ratio, playing a crucial role in regulating membrane stability and fluidity, as well as photosynthesis efficiency, which makes it an important research focus in crop species. This study reports the characterization and molecular cloning of pale dwarf (pad), a new tomato (Solanum lycopersicum L.) T-DNA recessive mutant, which exhibits a dwarf and chlorotic phenotype. Functional studies of the T-DNA tagged gene were conducted, including phylogenetic analysis, expression and metabolomic analyses, and generation of CRISPR/Cas9 knockout lines. The cloning of T-DNA flanking genomic sequences and a co-segregation analysis found the pad phenotype was caused by a T-DNA insertion disrupting the tomato homologue of the Arabidopsis SUPPRESSOR OF SALICYLIC ACID INSENSITIVITY 2 (SlSSI2), encoding a plastid localized isoform of SACPD. The phenotype of CRISPR/Cas9 SlSSI2 knockout lines confirmed that the morphological abnormalities in pad plants were due to SlSSI2 loss of function. Functional, metabolomic and expression analyses proved that SlSSI2 disruption causes deficiencies in 18:1 fatty acid desaturation and leads to diminished jasmonic acid (JA) content and increased salicylic acid (SA) levels. Overall, these results proved that SSI2 plays a crucial role in the regulation of polyunsaturated fatty acid profiles in tomato, and revealed that SlSSI2 loss of function results in an inhibited JA-responsive signalling pathway and a constitutively activated SA-mediated defence signalling response. This study lays the foundation for further research on tomato SACPDs and their role in plant performance and fitness.

Corneal endothelial validation in the eye bank: differences in automated methods and repeatability.

PURPOSE: To evaluate reproducibility of endothelial cell density (ECD) measurements using the Konan Cell Check D in donor corneas by two different ophthalmologists and to compare the two automated cell count methods (center and flex-center) available in the software of this specular microscope. METHODS: ECD values were quantified in 54 donor corneas by two independent investigators using the Cell Check D (Konan Medical USA Inc) with both automated cell count methods. In the center method, at least 30 contiguous cells are marked. For the flex-center method, an area is delineated and only the cells within the designated area are counted. RESULTS: The mean ECD was 2473.81±378.22 cells/mm2. Good ECD intergrader reproducibility for the center (ICC=0.821) and the flex-center method (ICC=0.784) were noted. Poor reliability was observed for coefficient of variation and hexagonality (ICC≤0.265). When both methods for ECD analysis were compared, a moderate correlation for the two independent graders using the two manual (center and flex-center) methods was detected (correlation coefficient of 0.678 and 0.745 for each of the investigators). Comparison between methods yielded significantly higher ECD with the flex-center method (P=0.013). When corneas were divided by ECD, those under 2200 cells/mm2 and those between 2200 and 2700 cells/mm2 also had significantly higher ECD with the flex-center method (P<0.022). CONCLUSIONS: ECD values are reproducible with both methods, although the flex-center method ECDs tend to be higher, particularly in cases of low ECD. Eye banks and surgeons should exercise caution in making decisions based only on small differences in ECD.

Radiological-pathological correlation in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): imaging and histopathology.

AIM: To review histologically confirmed diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) cases and carry out a detailed pathological-radiological correlation to see if computed tomography (CT) can be used to confidently identify DIPNECH. MATERIALS AND METHODS: Twenty-three histologically confirmed DIPNECH patients in the shared database of two NHS Trusts were reviewed. CT images were reviewed by two independent radiologists, each of them with >10 years of experience in thoracic imaging. All histological specimens were reviewed by a single pathologist with >25 years of experience. The diagnosis of DIPNECH was made according to the current World Health Organization (WHO) definition included in the WHO 2015 classification of pulmonary tumours. The results on histology were compared to the presence of nodules and air trapping on CT. Demographic information and, when available, molecular imaging studies and pulmonary function tests were also considered. RESULTS: There are prototypal clinical and radiological findings reflecting the presence of underlying histological DIPNECH: middle-aged women with multiple small and scattered nodules due to the clustering and proliferation of neuroendocrine cells. At least one larger, dominant, lung nodule reflecting a carcinoid tumour is very common and mosaic attenuation/air trapping is seen approximately in 50% of cases in inspiratory scans. Airflow obstruction is rarely associated with histological bronchial or peribronchial fibrosis, which suggests other mechanisms must be involved in its development. CONCLUSION: CT can be used to predict pathological DIPNECH in the appropriate clinical setting. It is important to consider DIPNECH to avoid overdiagnosis of more sinister conditions such as lung cancer or metastases.