Miopatías RYR1 en la infancia: correlación fenotipo-genotipo e incidencia / RYR1 myopathies in childhood: phenotype-genotype correlation and incidence

Introducción: Las miopatías relacionadas con el receptor de rianodina de tipo 1 (RYR1-RM) constituyen la categoría más frecuente de miopatías congénitas. La introducción de técnicas genéticas ha cambiado el paradigma diagnóstico y sugiere la prioridad de estudios moleculares sobre biopsias. Este estudio busca explorar las características clinicoepidemiológicas de pacientes con variantes del gen RYR1 en un hospital pediátrico de tercer nivel con el objetivo de ampliar la comprensión de la correlación genotipo-fenotipo en las RYR1-RM. Pacientes y métodos: Estudio observacional, descriptivo y transversal, de pacientes menores de 14 años con síntomas miopáticos y variantes potencialmente patógenas del gen RYR1 entre enero de 2013 y diciembre de 2023, considerando variables como sexo, edad, desarrollo motor, variantes genéticas, patrón de herencia y otras manifestaciones. Todas las variables fueron tabuladas frente a la variante genética. Resultados: De los nueve pacientes incluidos, la incidencia estimada fue de aproximadamente 1/10.000 nacidos vivos. La mediana en el momento del diagnóstico fue de 6 años, con una variabilidad fenotípica significativa. Se observaron síntomas comunes, como debilidad y retraso del desarrollo motor. Las variantes genéticas afectaron al gen RYR1 de manera diversa, y hubo cinco variantes previamente no descritas. La biopsia muscular se realizó en cinco pacientes, en dos de ellos de tipo miopatía central core; en uno, multiminicore; en uno, desproporción congénita de fibras; y en otro, de patrón inespecífico. Conclusiones: Las RYR1-MR de nuestra serie ofrecieron variabilidad fenotípica y de afectación, con una incidencia en nuestra área de en torno a 1/10.000 recién nacidos. La mayoría de los casos fueron varones, de variantes missense dominantes. Aportamos cinco variantes genéticas no descritas con anterioridad.(AU)

Introduction: Ryanodine receptor type 1-related myopathies (RYR1-RM) represent the most prevalent category of congenital myopathies. The introduction of genetic techniques has shifted the diagnostic paradigm, suggesting the prioritization of molecular studies over biopsies. This study aims to explore the clinical and epidemiological characteristics of patients with RYR1 gene variants in a tertiary pediatric hospital, intending to enhance the understanding of the genotype-phenotype correlation in RYR1-RM. Patients and methods: An observational, descriptive, and cross-sectional study was conducted on patients under 14 years old with myopathic symptoms and potentially pathogenic RYR1 gene variants from January 2013 to December 2023. Variables such as gender, age, motor development, genetic variants, inheritance pattern, and other manifestations were considered. All variables were tabulated against the genetic variant. Results: Of the nine included patients, the estimated incidence was approximately 1 in 10,000 live births. The median age at diagnosis was six years, with significant phenotypic variability. Common symptoms such as weakness and delayed motor development were observed. Genetic variants affected the RYR1 gene diversely, including five previously undescribed variants. Muscle biopsy was performed in five patients, revealing central core myopathy in two, multiminicore in one, congenital fiber-type disproportion in one, and a nonspecific pattern in another.(AU)

[RYR1 myopathies in childhood: phenotype-genotype correlation and incidence]. / Miopatías RYR1 en la infancia: correlación fenotipo-genotipo e incidencia.

INTRODUCTION: Ryanodine receptor type 1-related myopathies (RYR1-RM) represent the most prevalent category of congenital myopathies. The introduction of genetic techniques has shifted the diagnostic paradigm, suggesting the prioritization of molecular studies over biopsies. This study aims to explore the clinical and epidemiological characteristics of patients with RYR1 gene variants in a tertiary pediatric hospital, intending to enhance the understanding of the genotype-phenotype correlation in RYR1-RM. PATIENTS AND METHODS: An observational, descriptive, and cross-sectional study was conducted on patients under 14 years old with myopathic symptoms and potentially pathogenic RYR1 gene variants from January 2013 to December 2023. Variables such as gender, age, motor development, genetic variants, inheritance pattern, and other manifestations were considered. All variables were tabulated against the genetic variant. RESULTS: Of the nine included patients, the estimated incidence was approximately 1 in 10,000 live births. The median age at diagnosis was six years, with significant phenotypic variability. Common symptoms such as weakness and delayed motor development were observed. Genetic variants affected the RYR1 gene diversely, including five previously undescribed variants. Muscle biopsy was performed in five patients, revealing central core myopathy in two, multiminicore in one, congenital fiber-type disproportion in one, and a nonspecific pattern in another. CONCLUSIONS: RYR1-RM in our series exhibited phenotypic and involvement variability, with an incidence in our area of around 1 in 10,000 live births. Most cases were male, with dominant missense variants. We contribute five previously undescribed genetic variants.

TITLE: Miopatías RYR1 en la infancia: correlación fenotipo-genotipo e incidencia.Introducción. Las miopatías relacionadas con el receptor de rianodina de tipo 1 (RYR1-RM) constituyen la categoría más frecuente de miopatías congénitas. La introducción de técnicas genéticas ha cambiado el paradigma diagnóstico y sugiere la prioridad de estudios moleculares sobre biopsias. Este estudio busca explorar las características clinicoepidemiológicas de pacientes con variantes del gen RYR1 en un hospital pediátrico de tercer nivel con el objetivo de ampliar la comprensión de la correlación genotipo-fenotipo en las RYR1-RM. Pacientes y métodos. Estudio observacional, descriptivo y transversal, de pacientes menores de 14 años con síntomas miopáticos y variantes potencialmente patógenas del gen RYR1 entre enero de 2013 y diciembre de 2023, considerando variables como sexo, edad, desarrollo motor, variantes genéticas, patrón de herencia y otras manifestaciones. Todas las variables fueron tabuladas frente a la variante genética. Resultados. De los nueve pacientes incluidos, la incidencia estimada fue de aproximadamente 1/10.000 nacidos vivos. La mediana en el momento del diagnóstico fue de 6 años, con una variabilidad fenotípica significativa. Se observaron síntomas comunes, como debilidad y retraso del desarrollo motor. Las variantes genéticas afectaron al gen RYR1 de manera diversa, y hubo cinco variantes previamente no descritas. La biopsia muscular se realizó en cinco pacientes, en dos de ellos de tipo miopatía central core; en uno, multiminicore; en uno, desproporción congénita de fibras; y en otro, de patrón inespecífico. Conclusiones. Las RYR1-MR de nuestra serie ofrecieron variabilidad fenotípica y de afectación, con una incidencia en nuestra área de en torno a 1/10.000 recién nacidos. La mayoría de los casos fueron varones, de variantes missense dominantes. Aportamos cinco variantes genéticas no descritas con anterioridad.

Olive leaf protein: Extraction optimization, in vitro digestibility, structural and techno-functional properties.

Olive leaf, as an important by-product of olive farming, is generated from the pruning and harvesting of olive trees and represents >10 % of the total olive weight. The present study was conducted to evaluate the composition, functional and structural characterizations, as well as the in vitro digestibility of olive leaf proteins isolated from ultrasonic-assisted extraction, comparing to classical and industrial techniques. The ultrasound-assisted extraction of olive leaf protein was optimized by the simultaneous maximization of the yield and purity of protein using a Box-Behnken design (BBD) of response surface methodology (RSM). The results indicated that the optimal extraction conditions were as follows: pH of 10.99, temperature of 40.48 °C, sonication time of 47.25 min, and solvent/solid ratio of 24.08 mL/g. Under these conditions, the extraction yield and protein content were 11.67 and 51.2 %, respectively, which were significantly higher than those obtained by the conventional techniques. Regarding the functionality of protein, extraction technique had significant impacts on the structural and functional properties of proteins. In general, ultrasound assisted extraction had higher solubility, and better foaming and thermal properties and in vitro digestibility but lower emulsifying stability and fluid binding capacity compared to conventional ones. Ultrasound-assisted alkaline extraction has great potential to produce edible olive leaf protein with modified functional properties that can be used for various aims in the food applications.

Screws versus plate with screws for osteosynthesis of the posterior malleolus: a systematic review and meta-analysis.

INTRODUCTION: fractures involving the posterior malleolus (PM) of the ankle can have significant functional and clinical implications if not properly treated. The optimal treatment approach for these fractures remains uncertain. This review aims to compare the use of cannulated screws versus plate with screw fixation in terms of their impact on the development of postoperative ankle osteoarthritis and functional outcomes in patients with PM fractures. MATERIAL AND METHODS: a comprehensive search was conducted in PubMed, EMBASE, and Cochrane Library databases to identify studies directly comparing cannulated screws versus plate with screw fixation for PM fractures and their association with the development of postoperative osteoarthritis and functional outcomes. The quality of the included studies was assessed using appropriate assessment tools. The data on osteoarthritis development and functional outcomes were extracted and analyzed. RESULTS: a total of 691 articles were screened, and several studies were included for analysis. The findings revealed no statistically significant difference in the development of postoperative ankle osteoarthritis between the cannulated screws and plate with screw fixation groups. Similarly, there was no significant difference in functional outcomes between the two treatment approaches. CONCLUSION: based on the available evidence, there is no significant difference in the development of postoperative ankle osteoarthritis or functional outcomes between cannulated screws and plate with screw fixation for PM fractures. However, further research is needed to strengthen these findings and provide more conclusive evidence.

INTRODUCCIÓN: las fracturas que involucran el maléolo posterior (MP) del tobillo pueden tener importantes implicaciones funcionales y clínicas si no se tratan adecuadamente. El enfoque de tratamiento óptimo para estas fracturas sigue siendo incierto. El objetivo de esta revisión es comparar el uso de tornillos canulados versus placa con fijación de tornillos en cuanto a su impacto en el desarrollo de la osteoartrosis de tobillo postoperatoria y los resultados funcionales en pacientes con fracturas del MP. MATERIAL Y MÉTODOS: se realizó una búsqueda exhaustiva en las bases de datos de PubMed, EMBASE y Cochrane Library para identificar estudios que compararan directamente tornillos canulados versus placa con fijación de tornillos para fracturas de MP y su asociación con el desarrollo de osteoartrosis postoperatoria y los resultados funcionales. La calidad de los estudios incluidos se evaluó utilizando herramientas de evaluación adecuadas. Los datos sobre el desarrollo de osteoartrosis y los resultados funcionales se extrajeron y analizaron. RESULTADOS: se revisaron un total de 691 artículos y se incluyeron varios estudios para su análisis. Los hallazgos revelaron que no hay una diferencia estadísticamente significativa en el desarrollo de osteoartrosis de tobillo postoperatoria entre los grupos de tornillos canulados y placa con fijación de tornillos. Del mismo modo, no hubo una diferencia significativa en los resultados funcionales entre los dos enfoques de tratamiento. CONCLUSIÓN: según la evidencia disponible, no hay una diferencia significativa en el desarrollo de osteoartrosis de tobillo postoperatoria o en los resultados funcionales entre los tornillos canulados y la placa con fijación de tornillos para las fracturas del MP. Sin embargo, se necesita más investigación para fortalecer estos hallazgos y proporcionar evidencia más concluyente.

Isavuconazole-tacrolimus drug-drug interactions in HSCT patients.

OBJECTIVES: Because tacrolimus has a narrow therapeutic window and exhibits both intraindividual and interindividual variability, we attempted to establish the percentage of calcineurin inhibitor (CNI) dose reduction to prevent toxicity and ensure stem cell engraftment when using this immunosuppressant with the antifungal isavuconazole (ISA). By calculating the tacrolimus concentration/dose (C/D) ratio, we expected to demonstrate the magnitude of change in the C/D ratio from baseline after ISA administration. METHODS: We evaluated the interaction between ISA, a new triazole antifungal used in prophylaxis for invasive fungal infections, and the CNI class of immunosuppressive drugs, specifically tacrolimus, in 11 blood samples from HSCT recipients. RESULTS: The mean tacrolimus C/D ratio increased 1.44-fold from baseline 48 h after ISA administration (P = 0.001). CONCLUSIONS: Although further investigation is needed, the results of this study suggest that a reduction of 18% in tacrolimus may be recommended.

Targeted transcriptomic analysis of pancreatic adenocarcinoma in EUS-FNA samples by NanoString technology.

Background: Integration of transcriptomic testing into EUS-FNA samples is a growing need for precision oncology in pancreatic ductal adenocarcinoma (PDAC). The NanoString platform is suitable for transcriptome profiling in low yield RNA samples. Methods: Inclusion of patients that underwent EUS-FNA cytological diagnosis of pancreatic ductal adenocarcinoma using 19G and/or 22G needles and subsequent surgical resection. Formalin-fixed, paraffin-embedded (FFPE) cytological and surgical samples underwent RNA extraction and transcriptomic analysis using a custom 52-gene NanoString panel of stromal PDAC features. Cell type abundance was quantified in FFPE specimens and correlated. Results: 18 PDAC patients were included. Mean EUS-FNA passes was 2 + 0.7. All FFPE passed the RNA quality control for genomic analysis. Hierarchical clustering on the global gene expression data showed that genes were differentially expressed between EUS and surgical samples. A more enriched cancer-associated fibroblasts and epithelial-mesenchymal transition transcriptomic profile was observed across surgical specimens whereas immunological biomarkers were more represented in EUS-FNA samples. Cytological examination confirmed a scanty representation of CAF and more immunological cell abundance in cytological samples in comparison to surgical specimens. Conclusion: Targeted transcriptomic NanoString profiling of PDAC samples obtained by EUS-FNA is a feasible approach for pre-surgical molecular analysis although stromal CAF/EMT mRNA biomarkers are underrepresented.

Diagnosis and treatment of primary thyroid lymphoma from a surgical perspective: a multi-institutional study.

PURPOSE: Surgery of primary thyroid lymphoma (PTL) has been mostly limited to diagnostic work-up. This study aimed to further study its potential role. METHODS: This was a retrospective study from a multi-institutional registry of PTL patients. Clinical, diagnostic work-up (fine needle aspiration, FNA; core needle biopsy, CoreNB), contribution of surgery (open surgical biopsy, OpenSB; thyroidectomy), histology subtype, and outcome data were evaluated. RESULTS: Some 54 patients were studied. Diagnostic work-up included FNA in 47 patients, CoreNB in 11, and OpenSB in 21. CoreNB yielded the best sensitivity (90.9%). Thyroidectomy was performed in 14 patients with other diagnosis (incidental PTL), in 4 for diagnosis and in 4 for elective treatment of PTL. Incidental PTL was associated with not performed FNA nor CoreNB (OR 52.5; P = 0.008), mucosa-associated lymphoid tissue (MALT) subtype (OR 24.3; P = 0.012), and Hashimoto's thyroiditis (OR 11.1; P = 0.032). Lymphoma-related death (10 cases) mostly occurred within the first year after diagnosis and was associated with diffuse large B-cell (DLBC) subtype (OR 10.3; P = 0.018) and older patients (OR 1.08 for every 1-year increase; P = 0.010). There was a trend towards lower mortality rate in patients receiving thyroidectomy (2/22 versus 8/32, P = 0.172). CONCLUSION: Incidental PTL accounts for most of thyroid surgery cases and are associated with incomplete diagnostic work-up, Hashimoto's thyroiditis and MALT subtype. CoreNB appears to be the best tool for diagnosis. Most of PTL deaths occurred during the first year after diagnosis and mostly related to systemic treatment. Age and DLBC subtype are poor prognostic factors.

Effect of a resistance training programme implemented with high levels of effort on physical fitness in people with intellectual disabilities living in group homes: a randomised controlled trial.

BACKGROUND: The objective of this study was to evaluate the effectiveness of a 14-week resistance training programme implemented with high levels of effort to improve physical fitness in people with intellectual disabilities (IDs) living in group homes. METHODS: Fifty-two individuals with mild to moderate IDs participated in the experimental (n = 27; 15 men) or control groups (n = 25; 14 men). Participants performed 2 familiarisation sessions, 1 pretest, 42 training sessions (14 weeks × 3 sessions; only the experimental group) and 1 posttest. The testing sessions comprised the evaluation of body composition, static balance and muscle strength. The training sessions included four blocks: (1) dynamic bodyweight exercises, (2) dynamic exercises performed against external loads, (3) ballistic exercises and (4) static exercises. RESULTS: The main findings revealed that all variables related to body composition and muscle strength improved more after the intervention period in the experimental group than the control group, whereas the improvements in static balance for the experimental groups were lower than for the remaining variables used as markers of physical fitness. CONCLUSIONS: These findings highlight the importance of prescribing specific moderate-intensity to high-intensity resistance training programmes to improve body composition and muscle strength for people with IDs living in group homes.

Insights into the adsorption of CO2 generated from synthetic urban wastewater treatment on olive pomace biochar.

In this investigation, a sustainable and low-cost method to capture CO2 generated from the treatment of urban wastewater was evaluated. We studied the adsorption of CO2 on olive pomace biochar. The experiments of degradation of synthetic wastewater mimicking effluents of municipal wastewater treatment plant (WWTP) with an initial Total Organic Carbon (TOC) concentration of 10 mg L-1 were conducted by using the UV-C/H2O2 process in the absence or presence of biochar. The biochar was placed in a fixed bed column through which air from the UV reactor was circulated. First, the effects of different parameters such as H2O2 initial concentration and pH on wastewater mineralization efficiency were determined. Total Organic Carbon (TOC) removal was 87% in 2 h under optimal degradation conditions. The maximal concentration of CO2(gas) in air, in a closed system (air volume: 7.3 10-4 m3), after 11 h was 12,500 µmol mol-1 in the absence of biochar and only 150 µmol mol-1 when 10 g biochar were used. The results proved that by combining biochar with oxidative degradation of organic compounds, it is possible to mineralize organic compounds and reduce the requisite CO2 emissions by about 99%. The experimental equilibrium results were fit well with both Langmuir and Freundlich isotherms models concluding that CO2 adsorption on biochar followed both chemisorption and physisorption and both monolayer and multi-layer CO2 adsorption could occur. The total desorption of CO2 from biochar was reached in 120 min by simultaneously increasing the temperature to 150 °C and introducing a purge N2(gas).

Estudio observacional prospectivo del impacto de los problemas de acceso al tratamiento como factores de riesgo de la adherencia y persistencia. Estudio piloto / Prospective observational study of the impact of problems accessing treatment such as risk factors for adherence and persistence. Pilot study

Introducción: se han realizado algunos estudios preliminares que muestran la aparición de factores de riesgo no investigados previamente relativos al sistema sanitario que pueden reducir la adherencia y/o persistencia de los tratamientos farmacológicos. De su conocimiento se pueden explorar posibles soluciones. Objetivo: estimar la incidencia de los factores de riesgo relativos al sistema sanitario que pueden reducir la adherencia/persistencia a los tratamientos asociados a problemas de acceso a los mismos en farmacia comunitaria. Método: estudio prospectivo aleatorizado transversal en farmacias comunitarias del Principado de Asturias y Aragón. La variable principal es la incidencia de nuevos factores de riesgo que hacen que la prescripción sea inadecuada para su dispensación. Se analizan diferentes subgrupos en función de tipo de factor de riesgo, tipo de población y tipo de prescripción.Resultados: el paciente tipo es una persona vulnerable en función de su edad (65,4 años), pluripatología y polifarmacia (6,8 medicamentos). Tras la evaluación de 138.697 dispensaciones en 98 farmacias comunitarias se detectaron 2.009 pacientes con 2.221 dispensaciones con factores de riesgo frente a la adherencia y/o persistencia (1,6  % de del total de dispensaciones). El tipo de incidencia más frecuentemente observado fue caducidad de la receta (54,7 %; IC95 %=52,6-56,8), seguido de ausencia de receta (18,7 %; IC95 %: 17,1-20,3). Por su parte los problemas de suministro alcanzaron el 10,2 % (IC95 %= 10,6 %-10,9 %). Los grupos terapéuticos más comprometidos fueron los grupos N-Sistema Nervioso (27,6 %), C-Aparato Cardiovascular (20,3 %) y A-Aparato Digestivo (15,3 %) (AU)

Estrategia para optimizar la seguridad del paciente en el servicio de dispensación en farmacia comunitaria. Propuesta de listados de verificación / Strategy to optimize patient safety in community pharmacy dispensing service. Checklists Proposed

La dispensación es el servicio más demandado e importante dentro de las labores que realiza el farmacéutico, en su día a día, en la farmacia comunitaria. El objetivo de la dispensación es garantizar el acceso del paciente al medicamento de manera adecuada y controlada. En dicho proceso, el farmacéutico comunitario tiene la obligación, como profesional de la salud, de participar de forma activa y comprometida en la detección de posibles errores de medicación o relacionados con la misma. El Grupo de Trabajo de Seguridad del Paciente de SEFAC ha elaborado, como comienzo de una serie de futuros proyectos, unos listados de verificación y decálogos de buenas prácticas sobre medicamentos formulados en forma de parches transdérmicos, comprimidos bucodispersables o formas de liberación modificada. Con esta iniciativa se pretende, mediante una entrevista previa con el paciente y el uso de estas herramientas, minimizar en la medida de lo posible, los errores o problemas que puedan surgir con dichos medicamentos velando finalmente por la seguridad del paciente. A lo largo del 2023 se espera comenzar un pilotaje en farmacias comunitarias colaboradoras con el Grupo de Trabajo de Seguridad del paciente de SEFAC y así poder recoger y notificar los resultados que se obtengan (AU)

Insulin decreases epileptiform activity in rat layer 5/6 prefrontal cortex in vitro.

Accumulating evidence indicates that insulin-mediated signaling in the brain may play important roles in regulating neuronal function. Alterations to insulin signaling are associated with the development of neurological disorders including Alzheimer's disease and Parkinson's disease. Also, hyperglycemia and insulin resistance have been associated with seizure activity and brain injury. In recent work, we found that insulin increased inhibitory GABAA -mediated tonic currents in the prefrontal cortex (PFC). In this work, we used local field potential recordings and calcium imaging to investigate the effect of insulin on seizure-like activity in PFC slices. Seizure-like events (SLEs) were induced by perfusing the slices with magnesium-free artificial cerebrospinal fluid (ACSF) containing the proconvulsive compound 4-aminopyridine (4-AP). We found that insulin decreased the frequency, amplitude, and duration of SLEs as well as the synchronic activity of PFC neurons evoked by 4-AP. These insulin effects were mediated by the PI3K/Akt signaling pathway and mimicked by gaboxadol (THIP), a δ GABAA receptor agonist. The effect of insulin on the number of SLEs was partially blocked by L-655,708, an inverse agonist with high selectivity for GABAA receptors containing the α5 subunit. Our results suggest that insulin reduces neuronal excitability by an increase of GABAergic tonic currents. The physiological relevance of these findings is discussed.

Role of adjuvants in regional anesthesia: A systematic review.

The combination of drugs and routes of administration produces a synergistic effect, and one of the most important components of multimodal analgesic strategies are, therefore, nerve blocks for pain management. The effect of a local anaesthetic can be prolonged by administering an adjuvant. In this systematic review, we included studies on adjuvants associated with local anaesthetics in peripheral nerve blocks published in the last 5 years in order to evaluate their effectiveness. The results were reported according to the PRISMA guidelines. The 79 studies selected using our criteria showed a clear prevalence of dexamethasone (n=24) and dexmedetomidine (n=33) over other adjuvants. Different meta-analyses comparing adjuvants suggest that dexamethasone administered perineurally achieves superior blockade with fewer side effects than dexmedetomidine. Based on the studies reviewed, we found moderate evidence to recommend the use of dexamethasone as an adjuvant to peripheral regional anaesthesia in surgeries that can cause moderate to severe pain.

Papel de los coadyuvantes en la anestesia regional: revisión sistemática / Role of adjuvants in regional anesthesia: a systematic review

La combinación de fármacos y vías de administración consigue un efecto sinérgico, por eso las estrategias analgésicas multimodales incorporan bloqueos periféricos como componente imprescindible para un buen control del dolor. La asociación de un coadyuvante al anestésico local prolongaría su efecto. Esta revisión sistemática ha incluido estudios sobre coadyuvantes asociados a anestésicos locales en bloqueos periféricos publicados en los últimos cinco años. El objetivo principal ha sido evaluar su eficacia. Los resultados de la búsqueda se informaron de acuerdo con los elementos PRISMA. Los 79 artículos seleccionados según criterios, mostraron una clara prevalencia de dexametasona (n=24) y dexmedetomidina (n=33) sobre los demás coadyuvantes. Diferentes metaanálisis que comparan a los coadyuvantes sugieren un bloqueo de características superiores y menores efectos adversos con dexametasona vs. dexmedetomidina perineuralmente. Con base en los estudios, encontramos una evidencia moderada en el empleo de dexametasona como coadyuvante de la anestesia regional periférica en cirugías que generen dolor moderado- severo, lo que haría recomendable su empleo.(AU)

The combination of drugs and routes of administration produces a synergistic effect, and one of the most important components of multimodal analgesic strategies are, therefore, nerve blocks for pain management. The effect of a local anaesthetic can be prolonged by administering an adjuvant. In this systematic review, we included studies on adjuvants associated with local anaesthetics in peripheral nerve blocks published in the last 5 years in order to evaluate their effectiveness. The results were reported according to the PRISMA guidelines. The 79 studies selected using our criteria showed a clear prevalence of dexamethasone (n=24) and dexmedetomidine (n=33) over other adjuvants. Different meta-analyses comparing adjuvants suggest that dexamethasone administered perineurally achieves superior blockade with fewer side effects than dexmedetomidine. Based on the studies reviewed, we found moderate evidence to recommend the use of dexamethasone as an adjuvant to peripheral regional anaesthesia in surgeries that can cause moderate to severe pain.(AU)

Impact of plasmapheresis on severe COVID-19.

The clinical course of COVID-19 may show severe presentation, potentially involving dynamic cytokine storms and T cell lymphopenia, which are leading causes of death in patients with SARS-CoV-2 infection. Plasma exchange therapy (PLEX) effectively removes pro-inflammatory factors, modulating and restoring innate and adaptive immune responses. This clinical trial aimed to evaluate the impact of PLEX on the survival of patients with severe SARS-CoV-2 and the effect on the cytokine release syndrome. Hospitalized patients diagnosed with SARS-CoV-2 infection and cytokine storm syndrome were selected to receive 2 sessions of PLEX or standard therapy. Primary outcome was all-cause 60-days mortality; secondary outcome was requirement of mechanical ventilation, SOFA, NEWs-2 scores modification, reduction of pro-inflammatory biomarkers and hospitalization time. Twenty patients received PLEX were compared against 40 patients receiving standard therapy. PLEX reduced 60-days mortality (50% vs 20%; OR 0.25, 95%CI 0.071-0.880; p = 0.029), and this effect was independent from demographic variables and drug therapies used. PLEX significantly decreased SOFA, NEWs-2, pro-inflammatory mediators and increased lymphocyte count, accompanied with a trend to reduce affected lung volume, without effect on SatO2/FiO2 indicator or mechanical ventilation requirement. PLEX therapy provided significant benefits of pro-inflammatory clearance and reduction of 60-days mortality in selected patients with COVID-19, without significant adverse events.