Differences and Similarities in the Feet of Metatarsalgia Patients with and without Rheumatoid Arthritis in Remission.

Objectives: Metatarsalgia continues to be a problem in patients with rheumatoid arthritis (RA) in remission (remRA), as well as in the non-rheumatic population, with a mechanical origin. Identify and compare clinical, morphological, disability, synovitis (ultrasound), and radiological osteoarticular damage characteristics in two groups of patients with lesser-ray metar-tarsalgia, with remRA, and without RA. Methods: Cross-sectional study with 84 patients with remRA (mRA) and 60 patients without RA (nmRA). The study evaluated five clinical variables (pain, Foot Function Index (FFI), joint mobility, digital deformities, and foot type), a radiological variable (osteoarticular damage), and an ultrasound variable (metatarsal synovitis). The data were analysed using descriptive and correlational techniques. Results: There were no significant differences in sex, age, body mass index (BMI), or degree of pain. Both groups showed a high prevalence of limited joint mobility for the ankle and first metatarsal phalanx (DF1st MTPJ) and digital deformities, with no statistically significant differences. Similarly, there were no differences in lesser-ray synovitis. On the other hand, there were differences in mRA with greater disability and activity limitation (FFI), LDD (lesser-ray digital deformities) stiffness, first-ray deformities, radiological damage, synovitis in 1st MTPJ, and positive Doppler (five patients). Conclusions: Metatarsalgia presents similarities in both populations. Biomechanical factors may influence the symptoms and presence of synovitis in patients with RA in remission. Other characteristics are more frequent in mRA, which could be related to the disease; thus, future research should include both biomechanical and ultrasound exploration of the foot in the valuation of patients in remission.

Impact of minimal lumen segmentation uncertainty on patient-specific coronary simulations: A look at FFRCT.

We examined the effect of minimal lumen segmentation uncertainty on Fractional Flow Reserve obtained from Coronary Computed Tomography Angiography FFR CT $$ \left({\mathrm{FFR}}_{\mathrm{CT}}\right) $$ . A total of 14 patient-specific coronary models with different stenosis locations and degrees of severity were enrolled in this study. The optimal segmented coronary lumens were disturbed using intra ± 6 % $$ \left(\pm 6\%\right) $$ and inter-operator ± 15 % $$ \left(\pm 15\%\right) $$ variations on the segmentation threshold. FFR CT $$ {\mathrm{FFR}}_{\mathrm{CT}} $$ was evaluated in each case by 3D-OD CFD simulations. The findings suggest that the sensitivity of FFR CT $$ {\mathrm{FFR}}_{\mathrm{CT}} $$ to this type of uncertainty increases distally and with the stenosis severity. Cases with moderate or severe distal coronary lesions should undergo either exact and thorough segmentation operations or invasive FFR measurements, particularly if the FFR CT $$ {\mathrm{FFR}}_{\mathrm{CT}} $$ is close to the cutoff (0.80). Therefore, we conclude that it is crucial to consider the lesion's location and degree of severity when evaluating FFR CT $$ {\mathrm{FFR}}_{\mathrm{CT}} $$ results.

Optimal Prone Position Duration in Patients With ARDS Due to COVID-19: The Omelette Pilot Trial.

BACKGROUND: Prone position (PP) has been widely used in the COVID-19 pandemic for ARDS management. However, the optimal length of a PP session is still controversial. This study aimed to evaluate the effects of prolonged versus standard PP duration in subjects with ARDS due to COVID-19. METHODS: This was a single-center, randomized controlled, parallel, and open pilot trial including adult subjects diagnosed with severe ARDS due to COVID-19 receiving invasive mechanical ventilation that met criteria for PP between March-September 2021. Subjects were randomized to the intervention group of prolonged PP (48 h) versus the standard of care PP (∼16 h). The primary outcome variable for the trial was ventilator-free days (VFDs) to day 28. RESULTS: We enrolled 60 subjects. VFDs were not significantly different in the standard PP group (18 [interquartile range [IQR] 0-23] VFDs vs 7.5 [IQR 0-19.0] VFDs; difference, -10.5 (95% CI -3.5 to 19.0, P = .08). Prolonged PP was associated with longer time to successful extubation in survivors (13.00 [IQR 8.75-26.00] d vs 8.00 [IQR 5.00-10.25] d; difference, 5 [95% CI 0-15], P = .001). Prolonged PP was also significantly associated with longer ICU stay (18.5 [IQR 11.8-25.3] d vs 11.50 [IQR 7.75-25.00] d, P = .050) and extended administration of neuromuscular blockers (12.50 [IQR 5.75-20.00] d vs 5.0 [IQR 2.0-14.5] d, P = .005). Prolonged PP was associated with significant muscular impairment according to lower Medical Research Council values (59.6 [IQR 59.1-60.0] vs 56.5 [IQR 54.1-58.9], P = .02). CONCLUSIONS: Among subjects with severe ARDS due to COVID-19, there was no difference in 28-d VFDs between prolonged and standard PP strategy. However, prolonged PP was associated with a longer ICU stay, increased use of neuromuscular blockers, and greater muscular impairment. This suggests that prolonged PP is not superior to the current recommended standard of care.

Real-World Health Care Outcomes and Costs Among Patients With Juvenile Idiopathic Arthritis in Spain.

Background: Juvenile idiopathic arthritis (JIA) is the most frequent chronic rheumatic disease in children. If inflammation is not adequately treated, joint damage, long-term disability, and active disease during adulthood can occur. Identifying and implementing early and adequate therapy are critical for improving clinical outcomes. The burden of JIA on affected children, their families, and the healthcare system in Spain has not been adequately assessed. The greatest contribution to direct costs is medication, but other expenses contribute to the consumption of resources, negatively impacting healthcare cost and the economic conditions of affected families. Objective: To assess the direct healthcare, indirect resource utilization, and associated cost of moderate-to-severe JIA in children in routine clinical practice in Spain. Methods: Children were enrolled in this 24-month observational, multicentric, cross-sectional, retrospective study (N = 107) if they had been treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), had participated in a previous study (ITACA), and continued to be followed up at pediatric rheumatology units at 3 tertiary Spanish hospitals. Direct costs included medication, specialist and primary care visits, hospitalizations, emergency visits or consultations, surgeries, physiotherapy, and tests. Indirect costs included hospital travel expenses and loss of caregiver working hours. Unitary costs were obtained from official sources (€, 2020). Results: Overall, children had inactive disease/low disease activity according to JADAS-71 score and very low functional disability as measured by Childhood Health Assessment Questionnaire score. Up to 94.4% of children received treatment, mainly with bDMARDs as monotherapy (84.5%). Among anti-TNFα treatments, adalimumab (47.4%) and etanercept (40.2%) were used in similar proportions. Annual mean (SD) total JIA cost was €7516.40 (€5627.30). Average cost of pharmacological treatment was €3021.80 (€3956.20), mainly due to biologic therapy €2789.00 (€3399.80). Direct annual cost (excluding treatments) was €3654.60 (€3899.00). Indirect JIA cost per family was €747.20 (€1452.80). Conclusion: JIA causes significant costs to the Spanish healthcare system and affected families. Public costs are partly due to the high cost of biologic treatments, which nevertheless remain an effective long-term treatment, maintaining inactive disease/low disease activity state; a very low functional disability score; and a good quality of life.

Real-world Performance of a New Strategy for Off-Label Use of Guselkumab in Moderate to Severe Psoriasis: Super-Responder Patients as the Epitome of Efficacy and Optimisation.

BACKGROUND: Guselkumab is a drug used to treat moderate to severe plaque psoriasis. However, real-life clinical data on its off-label use are limited, especially regarding the optimal drug dosage regimen for different patient profiles. OBJECTIVE: The main objective of this real-world, single-centre, retrospective study was to identify the off-label guselkumab dosing regimen used in clinical practice. The study also aimed to evaluate the drug's efficacy, safety, and survival, as well as the proportion of super-responders (SR) based on a newly proposed definition. METHODS: The study included 69 patients who started treatment with guselkumab between March 2019 and July 2021. Patients were followed up until April 2022, during which time their efficacy, safety, persistence, and use of guselkumab were recorded. Patients were aged ≥  18 years and had moderate to severe plaque psoriasis. RESULTS: The mean disease duration was 18.6 years, and 59% of patients had received at least one biologic treatment before guselkumab with a mean of 1.3 biologics per patient. The initial absolute Psoriasis Area and Severity Index (PASI) was 10.1 and decreased to 2.1 between Week 11-20 without significant changes in the PASI value throughout the 90 weeks of follow-up. The cumulative probability of drug survival was 93.5% at Week 52. No differences were found in terms of efficacy and survival associated with the off-label drug dosage regimens compared to the doses described in the Summary of Product Characteristics (SmPC). The greatest adjustments in the drug administration regimen were achieved in the subgroups of bio-naïve and SR patients, with a reduction in the number of administrations by 40% and 47% compared to the regimen described in the SmPC. Super-response to guselkumab was mainly associated with patients naïve to previous biologic treatment. CONCLUSION: The study demonstrated that off-label use of guselkumab was safe and effective in real-life clinical practice. The findings suggest that adjustments to the drug administration regimen may be necessary to optimise its use in different patient profiles, especially in SR and bio-naïve patients. Further studies are needed to confirm these findings.

CHOICE international survey: Clusters of allergen immunotherapy prescription from French and Spanish cohorts.

Background: There is no description of the drivers of prescription for allergen immunotherapy (AIT) for respiratory allergic diseases. Methods: A prospective, multicentre, observational, non-interventional real-life study was performed in France and Spain for 20 months. Data were gathered using 2 different questionnaires, anonymously collected in an online platform. No names of AIT products were recorded. Multivariate analysis and unsupervised cluster analysis were performed. Results: One hundred and three physicians (50.5% from Spain and 49.5% from France) reported 1735 patients (433 in France and 1302 in Spain), 47.9% males, 64.8% adults with a mean age 26.2 years old. They suffered from allergic rhinitis (99%), allergic conjunctivitis (70.4%), allergic asthma (51.8%), atopic dermatitis (13.9%), and food allergy (9.9%). A clustering analysis based on 13 predefined relevant variables for AIT-prescription identified 5 different clusters, each of them including information regarding doctor's profile and patient demographics, baseline disease characteristics, and main AIT indication: 1) Looking at the future: focusing on asthma prevention (n = 355), 2) Efficacy after discontinuation of AIT (n = 293), 3) Fighting severe allergic disease (n = 322), 4) Looking at the present, facing current symptoms (n = 265) and 5) Doctor's own clinical experience (n = 500). Each one of these clusters have specific patients' and doctors' characteristics, representing distinctive AIT prescription drivers. Conclusion: Using data-driven analysis, we identified for the first time some reasons and patterns of AIT prescriptions in real-life clinical settings. There is no uniform indication for prescribing AIT, which varies amongst patients and doctors with multiple but specific drivers, taking into account several relevant parameters.

Long-Term Omalizumab in Elderly Patients with Chronic Urticaria: Is It a Safe Therapy?

BACKGROUND: Biologics have revolutionized the treatment of many diseases. In this regard, omalizumab (OMA), an anti-IgE monoclonal antibody, is the recommended therapeutic option for patients with chronic spontaneous urticaria (CSU) refractory to second-generation H1-antihistamines. Several studies confirm the efficacy and safety of the drug. However, the literature focusing on the elderly population is scarce, as this age group is often excluded from clinical trials. Therefore, the pharmacological treatment of CSU in elderly patients is a challenge that is increased by their comorbidities and consequent polypharmacy. OBJECTIVES: We describe the real-life safety profile of OMA in elderly patients (≥70 years) with CSU and chronic inducible urticaria (CIndU). We aimed to provide data for daily clinical practice in this vulnerable patient group. METHOD: A retrospective review was performed of the records of patients with CSU/CIndU from May 2003 to December 2019 in the Hospital Universitario La Paz. We describe qualitative and quantitative data according to measures of central tendency. Comparisons between qualitative and quantitative data were performed with the Mann-Whitney U test and the Fisher's test for qualitative variables. A p value <0.05 was considered statistically significant. RESULTS AND CONCLUSIONS: Eighty-nine patients were included, divided into two groups (<70 vs. ≥70 years). The overall rate of adverse events (AEs) was 48%, mainly mild. No association between age and AE was found (p = 0.789). No serious AE such as anaphylaxis was detected. CSU predominated in both groups. CIndU was less prevalent in the elderly (p = 0.017). There was no association between age and the other variables. Although the frequency of neoplasms was slightly higher in the elderly with OMA, we found no difference compared to the incidence of neoplasms in the general population. Therefore, our data suggest that OMA may be a safe treatment in elderly people with CSU/CIndU for prolonged periods of treatment, although further studies with larger samples are needed to corroborate our observations.

[Basophil activation test to follow-up of patients treated with hymenoptera venom immunotherapy: a review of current evidence]. / Prueba de activación de basófilos en el seguimiento de pacientes que reciben inmunoterapia con veneno de himenópteros: revisión de la evidencia actual.

Hymenoptera venom immunotherapy (HVI) is a long-term effective treatment to avoid new systemic reactions in patients with Hymenoptera allergy. The sting challenge test is considered the gold standard to confirm the tolerance. However, the use of this technique is not generalized in clinical practice, being the basophil activation test (BAT), which functionally explores allergen response, an alternative that does not entail any of the provocation risks associated with the sting challenge test. This study reviews the publications that used the BAT to follow up and evaluate the success of the HVI. Studies assessing the changes between a baseline BAT before the start and BATs performed between the starting and maintenance phases of the HVI were selected. Ten articles were found, comprising information from 167 patients, of which 29% used the sting challenge test. The studies concluded the importance of evaluating the responses with submaximal allergen concentrations, which reflect basophil sensitivity, to monitor the HVI using the BAT. It was also observed that changes in the maximum response (reactivity) could not reflect the clinical status of tolerance, particularly in the initial phases of HVI.

La inmunoterapia con veneno de himenópteros (IVH) es, a largo plazo, un tratamiento eficaz para evitar nuevas reacciones sistémicas en pacientes con alergia a este tipo de insectos. La prueba de repicadura controlada es el estudio de referencia para confirmar la tolerancia del individuo. Sin embargo, no se ha generalizado su indicación clínica, por lo que la prueba de activación de basófilos (TAB) resulta una buena alternativa, pues valora de manera funcional la respuesta al alérgeno y está exenta de los riesgos asociados con la provocación. En esta revisión se explora la utilidad de la TAB en el seguimiento y valoración del éxito de la IVH. Se seleccionaron estudios que evalúan los cambios entre una TAB basal y en otro momento de la fase de inicio o mantenimiento de la IVH. Se incluyeron 10 estudios con datos de 167 pacientes, de los que el 29% había tenido prueba de repicadura controlada. Para vigilar la eficacia de la IVH debe explorarse la respuesta del basófilo, con la determinación de las concentraciones submáximas del alérgeno, que reflejan la sensibilidad del basófilo. Los cambios en la respuesta máxima (reactividad) no pueden aportar información del estado de tolerancia, especialmente en las fases iniciales de la IVH.

Postoperative Blood Pressure Deficit and Acute Kidney Injury After Liver Transplant.

OBJECTIVES: Acute kidney injury is a common cause of morbidity in liver transplant recipients. In critically ill patients who received an orthotopic liver transplant, we examined whether those with acute kidney injury had a greater deficit between pretransplant and posttransplant hemodynamic pressure-related parameters compared with those without acute kidney injury in the early postoperative period. MATERIALS AND METHODS: We included patients who underwent an orthotopic liver transplant during the study period. We obtained premorbid and intensive care unit time-weighted average values for hemodynamic pressure-related parameters (systolic, diastolic, and mean arterial pressure; central venous pressure; mean perfusion pressure; and diastolic perfusion pressure) and calculated deficits in those values. We defined acute kidney injury progression as an increase of ≥1 Kidney Disease: Improving Global Outcomes stage. RESULTS: We included 150 eligible transplantrecipients, with 88 (59%) having acute kidney injury progression. Acute kidney injury was associated with worse clinical outcomes. All achieved pressure-related values were similar between transplant recipients with or without acute kidney injury progression. However, those with acute kidney injury versus those without progression had greater diastolic perfusion pressure deficit at 12 hours (-8.33% vs 1.93%; P = .037) and 24 hours (-7.38% vs 5.11%; P = .002) and increased central venous pressure at 24 hours (46.13% vs 15%; P = .043) and 48 hours (40% vs 20.87%; P = .039). CONCLUSIONS: Patients with acute kidney injury progression had a greater diastolic perfusion pressure deficit and increased central venous pressure compared with patients without progression. Such deficits might be modifiable risk factors for the prevention of acute kidney injury progression.

Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage.

Background: Neuropathic pain is one of the most difficult to treat chronic pain syndromes. It has significant effects on patients' quality of life and substantially adds to the burden of direct and indirect medical costs. There is a critical need to improve therapies for peripheral nerve regeneration. The aim of this study is to address this issue by performing a detailed analysis of the therapeutic benefits of two treatment options: adipose tissue derived-mesenchymal stem cells (ASCs) and ASC-conditioned medium (CM). Methods: To this end, we used an in vivo rat sciatic nerve damage model to investigate the molecular mechanisms involved in the myelinating capacity of ASCs and CM. Furthermore, effect of TNF and CM on Schwann cells (SCs) was evaluated. For our in vivo model, biomaterial surgical implants containing TNF were used to induce peripheral neuropathy in rats. Damaged nerves were also treated with either ASCs or CM and molecular methods were used to collect evidence of nerve regeneration. Post-operatively, rats were subjected to walking track analysis and their sciatic functional index was evaluated. Morphological data was gathered through transmission electron microscopy (TEM) of sciatic nerves harvested from the experimental rats. We also evaluated the effect of TNF on Schwann cells (SCs) in vitro. Genes and their correspondent proteins associated with nerve regeneration were analyzed by qPCR, western blot, and confocal microscopy. Results: Our data suggests that both ASCs and CM are potentially beneficial treatments for promoting myelination and axonal regeneration. After TNF-induced nerve damage we observed an upregulation of c-Jun along with a downregulation of Krox-20 myelin-associated transcription factor. However, when CM was added to TNF-treated nerves the opposite effect occurred and also resulted in increased expression of myelin-related genes and their corresponding proteins. Conclusion: Findings from our in vivo model showed that both ASCs and CM aided the regeneration of axonal myelin sheaths and the remodeling of peripheral nerve morphology.

Extracellular vesicle and soluble fractions of adipose tissue-derived mesenchymal stem cells secretome induce inflammatory cytokines modulation in an in vitro model of discogenic pain.

BACKGROUND CONTEXT: Mesenchymal stem cells (MSCs) secretome or conditioned medium (CM) is a complex cocktail of different molecules, some of which, particularly those contained in extracellular vesicles, already have proven therapeutic applications. PURPOSE: CM may well represent promising therapy for discogenic pain and the intention of this work is to assess its therapeutic potential using an in vitro model of this condition. STUDY DESIGN: This is an experimental study. METHODS: Our in vitro model comprised nucleus pulposus (NP) and annulus fibrosus (AF) cells inflamed with TNF. To assess the potential therapeutic value of CM and its components, extracellular vesicles (EVs) and soluble culture fraction (SF), cell inflammation took place under 3 different conditions: either in the presence of whole CM, isolated EVs or SF, and concentrations of pro-inflammatory cytokines, metalloproteinases (MMPs) and neurotrophic factors produced in all 3 cases were compared. RESULTS: In the presence of whole CM, both in vitro gene expression by the NP and AF test cells and analysis of their protein content showed high modulatory effects on inflammation and MMP inhibition. The presence of EVs and SF showed similar but much smaller effects, and this was particularly marked in the case of NP cells. CONCLUSIONS: Our results show that, compared to EVs and SF, the presence of whole CM has the greatest positive effect on the modulation of pro-inflammatory and catabolic factors. These observations suggest that CM could protect against inflammation and the resulting intervertebral disc (IVD) degeneration that leads to discogenic pain. CLINICAL SIGNIFICANCE: Many patients' expectations are not met by current non-operative and surgical treatments for discogenic low back pain. We propose the use of the MSCs secretome for assessing its potential as cell-free therapy to treat degenerative disc disease modulating the inflammatory response.

The paediatric foot: prevalence and differentiation of sonographic and podiatric findings in juvenile arthritis and healthy children.

OBJECTIVES: We aimed to, first, determine the prevalence of ultrasound (US) findings and podiatric anomalies in the paediatric foot, and to compare these findings between healthy and asymptomatic juvenile idiopathic arthritis (JIA) subjects, and then to analyse the associations between US and podiatric findings. METHODS: Healthy children and asymptomatic JIA patients underwent US and podiatric assessments. Grey-scale (GS) findings and Doppler signal in the joint recess, the tendon sheath and the enthesis of paediatric feet were assessed as present or absent. The podiatry assessment included: Foot Posture Index (FPI), footprint, standing heel-rise test, mobility of first toe and the Jack test. RESULTS: Forty-six children had at least one US finding (25 of 54 healthy children and 20 of 28 asymptomatic JIA patients). GSUS findings at the first metatarsophalangeal joint recess and physiological vascularisation at several locations were the most frequently detected findings in both groups. GSUS findings at the tibiotalar and subtalar joints were only detected in the JIA group. In comparison to the healthy group, the JIA group showed a trend towards pronated foot with abnormal footprint. However, the tibiotalar synovitis was significantly associated with supinated FPI. CONCLUSIONS: Improving the knowledge of US findings in the paediatric foot is crucial to evaluate properly children with suspected inflammatory diseases. US, in addition to podiatric assessment, would enable paediatric rheumatologists to discriminate between normal physiological findings and pathological abnormalities in asymptomatic children having JIA. Further studies are needed to confirm it.

Encuesta a profesionales sanitarios y pacientes sobre el papel del farmacéutico en la Unidad de Enfermedades Inflamatorias Inmunomediadas / The role of the pharmacist within an immune-mediated inflammatory disease unit: Results of a survey of healthcare providers and patients

Objetivo: Evaluar el interés y necesidad de que el farmacéutico desarrolle nuevas actividades propuestas, y potenciar o mantener otras que yase realizaban, antes de que la futura Unidad de Enfermedades Inflamatorias Inmunomediadas inicie su actividad en nuestro hospital. Además,priorizar la incorporación de las nuevas actividades en base a los resultados obtenidos.Método: Diseño observacional transversal unicéntrico mediante unaencuesta realizada en enero de 2020 a todos los profesionales sanitarios de los servicios clínicos implicados y a una muestra de pacientes, yestructurada en dos categorías: Acciones orientadas a la atención farmacéutica al paciente y Acciones orientadas a los profesionales de dichaUnidad. Cada ítem se puntuó de 0 a 10, siendo 10 el máximo interés/necesidad. Se aplicó una matriz de priorización para cuantificar y evaluar cada actividad e implantar las nuevas por orden de priorización.Resultados: Se completaron 90 encuestas (30 de pacientes y 60 deprofesionales). Se analizaron las medianas obtenidas de cada una de las20 actividades propuestas, alcanzándose valores entre 8 y 10. Se compararon valores: en el grupo de farmacéuticos versus médicos se obtuvieron más ítems con diferencias estadísticamente significativas que en elgrupo farmacéuticos versus enfermería, o farmacéuticos versus pacientes. (AU)

Objective: To evaluate the importance and need for pharmacists toexpand their role to new activities and to promote and maintain othersthey already carried out prior to the implementation of a new Immunemediated Inflammatory Diseases Unit to be created in our hospital; toprioritize the new activities incorporated based on the results obtained.Method: This was a single center cross-sectional based on a survey administered during January 2020 to all clinical healthcare providers due to bepart of the new unit, as well as to a sample of patients. It was structuredinto two categories: actions related to patients’ pharmaceutical care, andactions related to practitioners of the Immune-mediated Inflammatory Diseases Unit. Each item was assigned a score from 0 to 10, where 10 indicatedmaximum interest or need. A prioritization template was applied to quantifyand evaluate each activity and implement the new ones in order of priority.Results: A total of 90 responses were obtained (30 from patients and60 from healthcare workers). An analysis was performed of the medianscores of each of the 20 activities proposed, which ranged between 8 and10 points. When comparing the scores obtained, it was observed thatmore statistically significant differences were obtained in the pharmacists vsdoctors group than in the pharmacists vs nurses group, or the pharmacistsvs patients one. After prioritization, the first action taken was to implement electronic prescriptions for outpatients with immune-mediated inflammatorydiseases. (AU)

The role of the pharmacist within an immune-mediated inflammatory disease unit: Results of a survey of healthcare providers and patients.

OBJECTIVE: To evaluate the importance and need for pharmacists to expand  their role to new activities and to promote and maintain others they already  carried out prior to the implementation of a new Immunemediated Inflammatory Diseases Unit to be created in our hospital; to prioritize the new activities incorporated based on the results obtained. METHOD: This was a single center cross-sectional based on a survey  administered during January 2020 to all clinical healthcare providers due to be part of the new unit, as well as to a sample of patients. It was structured into two categories: actions related to patients' pharmaceutical  care, and actions related to practitioners of the Immune-mediated  Inflammatory Diseases Unit. Each item was assigned a score from 0 to 10,  where 10 indicated maximum interest or need. A prioritization template was  applied to quantify and evaluate each activity and implement the new ones in  order of priority. RESULTS: A total of 90 responses were obtained (30 from patients and 60 from  healthcare workers). An analysis was performed of the median scores of each  of the 20 activities proposed, which ranged between 8 and 10 points. When  comparing the scores obtained, it was observed that more statistically  significant differences were obtained in the pharmacists vs doctors group than  in the pharmacists vs nurses group, or the pharmacists vs patients one. After  prioritization, the first action taken was to implement electronic prescriptions  for outpatients with immune-mediated inflammatory diseases. CONCLUSIONS: The survey revealed the expectations of healthcare providers and patients regarding the role pharmacists should play in the newly created unit and provided an insight into the most valued activities. This information will be useful in prioritizing the implementation of the new activities to be carried out by the unit.

Objetivo: Evaluar el interés y necesidad de que el farmacéutico desarrolle nuevas actividades propuestas, y potenciar o mantener otras que ya se realizaban, antes de que la futura Unidad de Enfermedades Inflamatorias Inmunomediadas inicie su actividad en nuestro hospital. Además, priorizar la incorporación de las nuevas actividades en base a los  resultados obtenidos.Método: Diseño observacional transversal unicéntrico mediante una encuesta  realizada en enero de 2020 a todos los profesionales sanitarios de los servicios  clínicos implicados y a una muestra de pacientes, y estructurada en dos  categorías: Acciones orientadas a la atención farmacéutica al paciente y  Acciones orientadas a los profesionales de dicha Unidad. Cada ítem se puntuó  de 0 a 10, siendo 10 el máximo interés/necesidad. Se aplicó una matriz de  priorización para cuantificar y evaluar cada actividad e implantar las nuevas  por orden de priorización.Resultados: Se completaron 90 encuestas (30 de pacientes y 60 de profesionales). Se analizaron las medianas obtenidas de cada una de las 20  actividades propuestas, alcanzándose valores entre 8 y 10. Se compararon valores: en el grupo de farmacéuticos versus médicos se  obtuvieron más ítems con diferencias estadísticamente significativas que en el grupo farmacéuticos versus enfermería, o farmacéuticos versus pacientes. Tras la priorización, la primera acción fue implantar la prescripción electrónica en pacientes externos con enfermedades inflamatorias inmunomediadas.Conclusiones: La encuesta ha permitido conocer las expectativas de los  profesionales sanitarios y pacientes sobre la actividad del farmacéutico en  dicha Unidad, cuantificar las actividades más valoradas y priorizar la  implantación de nuevas actividades.

Real-World Experience with Two-Drug Regimens in HIV-1-Infected Patients Beyond the Indication of Clinical Trials: 48 Weeks' Results.

Data on two-drug regimens (2DRs) have shown high efficacy and tolerability in treatment-naive and treatment-experienced HIV-1 patients. Current guidelines recommend 2DRs as alternative to three-drug regimens (3DRs) to reduce long-term drug exposure and costs. Nevertheless, real-world experience with 2DR is limited. This study assessed the use of 2DR in routine clinical practice in a tertiary hospital. A retrospective, observational, descriptive study was performed on the use of dual therapy in adult HIV-1 patients. Individuals on antiretroviral treatment (ART) with dolutegravir plus lamivudine or dolutegravir plus rilpivirine who started 2DR between November 1, 2018, and April 30, 2019, were eligible for our study. Follow-up period was 48 weeks. Overall, 112 patients started 2DR; median age was 51 years and 88.4% were men. Most patients (97.3%) were treatment experienced before dual therapy, with 9.6 ± 8.0 years of prior ART on average. Around 96.4% of patients were virologically suppressed before 2DR. Most common reasons to start dual therapy were treatment simplification (49.5%), avoidance of long-term toxicities (21.1%), and intolerance to previous ART (18.3%). The main regimen used in dual therapy was dolutegravir plus lamivudine (98.2%). Only eight patients discontinued dual therapy; the main reason for discontinuation was toxicity. All patients who did not discontinue 2DR were virologically suppressed at week 48. ART simplification saved €130,117.58 during the study period. In our cohort, dual therapy was mainly used for virologically suppressed patients, before availability of the single-tablet 2DR. Switching to a 2DR may be a key option for treatment simplification and avoidance of long-term toxicities. Furthermore, 2DR could provide a more cost-effective alternative to 3DR.

Clinical Characteristics and Risk Factors of Respiratory Failure in a Cohort of Young Patients Requiring Hospital Admission with SARS-CoV2 Infection in Spain: Results of the Multicenter SEMI-COVID-19 Registry.

BACKGROUND: Age is a risk factor for COVID severity. Most studies performed in hospitalized patients with SARS-CoV2 infection have shown an over-representation of older patients and consequently few have properly defined COVID-19 in younger patients who require hospital admission. The aim of the present study was to analyze the clinical characteristics and risk factors for the development of respiratory failure among young (18 to 50 years) hospitalized patients with COVID-19. METHODS: This retrospective nationwide cohort study included hospitalized patients from 18 to 50 years old with confirmed COVID-19 between March 1, 2020, and July 2, 2020. All patient data were obtained from the SEMI-COVID Registry. Respiratory failure was defined as the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) ≤200 mmHg or the need for mechanical ventilation and/or high-flow nasal cannula or the presence of acute respiratory distress syndrome. RESULTS: During the recruitment period, 15,034 patients were included in the SEMI-COVID-19 Registry, of whom 2327 (15.4%) were younger than 50 years. Respiratory failure developed in 343 (14.7%), while mortality occurred in 2.3%. Patients with respiratory failure showed a higher incidence of major adverse cardiac events (44 (13%) vs 14 (0.8%), p<0.001), venous thrombosis (23 (6.7%) vs 14 (0.8%), p<0.001), mortality (43 (12.5%) vs 7 (0.4%), p<0.001), and longer hospital stay (15 (9-24) vs 6 (4-9), p<0.001), than the remaining patients. In multivariate analysis, variables associated with the development of respiratory failure were obesity (odds ratio (OR), 2.42; 95% confidence interval (95% CI), 1.71 to 3.43; p<0.0001), alcohol abuse (OR, 2.40; 95% CI, 1.26 to 4.58; p=0.0076), sleep apnea syndrome (SAHS) (OR, 2.22; 95% CI, 1.07 to 3.43; p=0.032), Charlson index ≥1 (OR, 1.77; 95% CI, 1.25 to 2.52; p=0.0013), fever (OR, 1.58; 95% CI, 1.13 to 2.22; p=0.0075), lymphocytes ≤1100 cells/µL (OR, 1.67; 95% CI, 1.18 to 2.37; p=0.0033), LDH >320 U/I (OR, 1.69; 95% CI, 1.18 to 2.42; p=0.0039), AST >35 mg/dL (OR, 1.74; 95% CI, 1.2 to 2.52; p=0.003), sodium <135 mmol/L (OR, 2.32; 95% CI, 1.24 to 4.33; p=0.0079), and C-reactive protein >8 mg/dL (OR, 2.42; 95% CI, 1.72 to 3.41; p<0.0001). CONCLUSIONS: Young patients with COVID-19 requiring hospital admission showed a notable incidence of respiratory failure. Obesity, SAHS, alcohol abuse, and certain laboratory parameters were independently associated with the development of this complication. Patients who suffered respiratory failure had a higher mortality and a higher incidence of major cardiac events, venous thrombosis, and hospital stay.

Isolation and morphological characterization of equine mesenchymal stem cells from harvested adipose tissue and bone marrow and stably transfected with green fluorescent protein.

OBJECTIVE: To characterize the ultrastructure of mesenchymal stem cells (MSCs) that were harvested from the adipose tissue (AT-MSCs) and bone marrow (BM-MSCs) of horses and transfected with green fluorescent protein. SAMPLE: MSCs from adipose tissue and bone marrow of 6 adult female Hispano-Bretón horses. PROCEDURES: Harvested equine MSCs were cultivated and transfected with green fluorescent protein, and the immunophenotypes of the MSCs were characterized by use of anti-CD90 and anti-CD105 monoclonal antibodies. When stable transfection of MSCs was achieved, the morphological and ultrastructural characteristics of transfected and nontransfected AT-MSCs and BM-MSCs were compared with electron microscopy. RESULTS: The protocols for transfection and subsequent isolation of transfected cells with use of G418 were suitable for obtaining transfected MSCs. Transfection efficiency was 5% in AT-MSCs and 4% in BM-MSCs. Characterization of transfected and nontransfected MSCs revealed that they share immunocytochemical and morphological profiles. Expression of CD90 was significantly higher for transfected versus nontransfected AT-MSCs (97% vs 92%). Expression of CD105 was significantly lower for transfected versus nontransfected BM-MSCs (85% vs 94%). Transfected BM-MSCs had differences in organelles, compared with the other cell types, specifically including most commonly the rough endoplasmic reticulum with dilated cisternae and mitochondria. CONCLUSION AND CLINICAL RELEVANCE: These findings contribute to the knowledge base of the characteristics of equine AT-MSCs and BM-MSCs and of transfected versus nontransfected equine MSCs. The data provided a valuable starting point for researchers wishing to further study the morphological characteristics of equine MSCs.

Multidisciplinary approach in the treatment of tendinous foot involvement in rheumatoid arthritis.

INTRODUCTION: Patients with rheumatoid arthritis frequently consult for pain resulting from involvement of the tendons of the foot. This pain negatively affects foot biomechanics and quality of life. The most widely used treatment option for this condition is ultrasound-guided steroid injection, while other treatments were recommended such as heel pad, splints, and footwear. OBJECTIVE: To evaluate a joint intervention (rheumatology and podiatry) comprising an orthotic-podiatric treatment and infiltrations. We evaluated the response using ultrasound monitoring, a pain scale, functional tests, and assessment of patient satisfaction. METHODS: We performed a non-controlled blinded prospective interventional study of 96 patients with foot pain and selected those with ultrasound-confirmed tendon involvement. Patients enrolled started intervention treatment and were followed for 6 months. The outcome of the intervention was compared with the patient's baseline status. The pre-post differences in the secondary variables (pain, disability) were analyzed using the t test and contingency tables or the Mann-Whitney test. RESULTS: Using our protocol, we recorded a rapid and significant reduction in the intensity of pain, in the foot function index, and in the ultrasound parameters (grayscale and Doppler). Structural damage to the tendon improved more slowly, with significant outcomes only at the last visit with respect to baseline. Abnormal foot support was detected in 50% of patients, and 79.5% were using inappropriate footwear. CONCLUSIONS: Our multidisciplinary therapeutic protocol enabled a very significant improvement in tendon involvement. It was well-tolerated, with a high degree of satisfaction, and was easily evaluated using ultrasound. No changes in background medication were necessary. Key Points • Multidisciplinary evaluation of patients with RA is advisable because it improves the treatment management in cases of inflammatory activity and structural abnormalities of the foot. • Comprising orthopedic-podiatric treatment (heel, splints, and suitable footwear) and infiltrations, in terms of clinical, ultrasound, and functional recovery of the foot tendons. • The therapy protocol we propose led to a significant improvement in pain relief and functional recovery.

Effect of mesenchymal stem cells combined with chondroitin sulfate in an in vitro model of osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease affecting the whole joint structure. The specific molecules responsible for the inflammatory processes involved in the development of OA have been the focus of many studies. Adipose tissue-derived mesenchymal stem cells (ASCs) constitute a promising cell-based therapy which could be used as an alternative to or in combination with drug therapies. Chondroitin sulfate (CS) plays a protective role in the joint by decreasing concentrations of pro-inflammatory cytokines and therefore has an important part in moderating chondrocyte metabolism. The aim of this study is to use an in vitro model of OA to evaluate the combined effectiveness of CS and ASCs as a treatment. We give a detailed discussion of the roles of cytokines and other key molecules involved in OA. In addition, we report the effects of treating inflamed chondrocytes with ASCs and CS on the expression of specific cartilage genes. Findings show that both treatments reduced expression of all genes associated with the pro-inflammatory cytokines we analyzed. However, we saw no increase in the expression of the specific genes encoding for cartilage matrix proteins, such as collagen type II and aggrecan. This study shows the effectiveness of combining ASCs and CS in the treatment of OA.