Safety and Effectiveness of Percutaneous Ultrasound-Guided Galvanic Current in Tunnels of Patients with Hidradenitis Suppurativa: A Pilot Study.

INTRODUCTION: The recurrent nature of hidradenitis suppurativa (HS), even under maintained systemic treatment, makes it necessary to have effective local treatments; however, the response to these therapies is variable (44-81%). The application of galvanic current (GC) has demonstrated its utility in humans in treating lesions structurally similar to those of HS. With this background, the main objective of this study was to evaluate the efficacy and safety of ultrasound-guided percutaneous GC in inflamed and/or draining tunnels of HS. METHODS: This was an open study (one-way repeated measures design over time). Patients were evaluated at 4 and 12 weeks after receiving GC. A combined clinical response at week 12 (absence of suppuration/inflammation on examination and clinical interview) was considered the principal variable of efficacy. Adverse effects potentially associated with GC were reported by telephone and at each visit. RESULTS: Twenty-six patients were included, with a male/female ratio of 5:8. The mean age was 35.84 (13.14) years. At 12 weeks after the administration of GC, a complete response was achieved in 77% (20/26) of the treated lesions. No serious adverse effects were observed, and the mean procedural pain assessed by the numeric rating scale was 0.03 (0.2). CONCLUSION: GC has proven to be effective and well tolerated in inflamed and draining tunnels of patients with HS.

Técnicas complementarias de relajación y analgesia no farmacológicas durante el parto: revisión sistemática / Complementary techniques of relaxation and non-pharmacological analgesia during childbirth: systematic review

Introducción: Existe la necesidad de proporcionar estrategias de analgesia que alienten y promuevan la participación de la mujer en la toma de decisiones en el momento del parto y las técnicas de relajación podrían ser un método analgésico no far-macológico complementario y/o alternativo a la anestesia epidural ampliamente utilizado. en la estándar atención del trabajo de parto. Objetivo: El objetivode este estudio es analizar los efectos obstétricos de las técnicas de relajación en el manejo del dolor durante el parto. Método: Se realiza una revisión sistemática con lectura crítica de los estudios incluidos. La búsqueda de estudios se realizó en las principales bases de datos MEDLINE, Cochrane Library, Cuiden, LILACS y SciELO. Se incluyen estudios publicados en inglés o español entre 2015 y febrero de 2021. Se incluyen una vez estudios, seis de los cuales son revisados sistemáticamente y cinco son ensayos clínicos aleatorios. Las intervenciones analizadas fueron técnicas de relajación como hipnosis, inyección intradérmica de agua estéril, inmersión en agua tibia, masaje, acu-puntura, musicoterapia, aromaterapia, apoyo continuo y prácticas mente-cuerpo como respiración relajante, yoga y meditación, entre otras. Conclusión: La principal conclusión de este estudio es que las técnicas de relajación pueden disminuir el nivel de dolor durante el trabajo, aunque la evidencia científica actual es limitada y la calidad metodológica varía de baja a moderada. Se necesitan más ensayos controlados aleatorios para apoyar esta investigación (AU)

Introduction:There is a need to provide analgesia strategies that encourage and promote women's participation in decision-making at the time of delivery and relaxation techniques could be a complementary and/or alternative non-pharmacological analgesic method to the widely used epidural anaesthesia in standard labour care. Objective: Theobjective of this study is to analyze the obstetric effects of relaxation techniques on pain management during labour. Method: A systematic review is performed with critical reading of included studies. The search for studies was carried out in the main databases MEDLINE, Cochrane Library, Cuiden, LILACS and SciELO. Studies published in English or Spanish between 2015 and February 2021 were included. Eleven studies were included, six of which are systematic reviews and five are randomised clinical trials. The interventions analysed were relaxation techniques such as hypnosis, intradermal injection of sterile water, warm water immersion, massage, acupuncture, music therapy, aromatherapy, continuous support and mind-body practices like relaxing breathing, yoga and meditation, among others. Conclusion: The main conclusion of this study is that relaxation techniques may decrease the level of pain during labour, although the current scientific evidence is limited and the methodological quality varies from low to moderate. More randomised controlled trials are needed to support this research (AU)

The 5-STS is a prognostic factor of sub-acute stroke patients who will not become community walkers at discharge from rehabilitation.

BACKGROUND: The recovery of community ambulation is a common concern among individuals after stroke. OBJECTIVES: (1) To develop a potential readily applicable prognostic model able to correctly discriminate stroke patients who will not become independent community walkers at discharge; (2) To investigate the effects of early reassessment during the first month of treatment on the prediction accuracy of this model. METHODS: This was a prospective cohort study. A consecutive sample of 80 patients at ≤60 days poststroke were assessed at baseline of outpatient physical rehabilitation and reassessed one month later. Non-functional community ambulation was measured. RESULTS: Seventy-four patients were followed until discharge. Of these, 47 patients were non-functional community walkers at discharge. A prediction model based on baseline performance in the five repetition sit-to-stand [5-STS] test was able to discriminate those patients of the sample (Area-under-curve = 0.956), and again with data from reassessment (AUC = 0.952). A time of 21 s at baseline was a highly prognostic cut-off point for discrimination (sensitivity = 87.2% and 85.1%). The combined use of baseline and reassessment data improved sensitivity (98.1%)CONCLUSION:Early findings of the 5-STS among stroke patients is an independent prognostic factor associated with independent community walking at discharge. It could discriminate individuals who will not become community walkers at discharge.

Cytotoxic evaluation of YSL-109 in a triple negative breast cancer cell line and toxicological evaluations.

Breast cancer (BC) is the leading cause of cancer-related death in women worldwide. Triple negative breast cancer (TNBC) is the most aggressive form of BC being with the worst prognosis and the worst survival rates. There is no specific pharmacological target for the treatment of TNBC; conventional therapy includes the use of non-specific chemotherapy that generally has a poor prognosis. Therefore, the search of effective therapies against to TNBC continues at both preclinical and clinical level. In this sense, the exploration of different pharmacological targets is a continue task that pave the way to epigenetic modulation using novel small molecules. Lately, the inhibition of histone deacetylases (HDACs) has been explored to treat different BC, including TNBC. HDACs remove the acetyl groups from the ɛ-amino lysine resides on histone and non-histone proteins. In particular, the inhibition of HDAC6 has been suggested to be useful for the treatment of TNBC due to it is overexpressed in TNBC. Therefore, in this work, an HDAC6 selective inhibitor, the (S)-4-butyl-N-(1-(hydroxyamino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl) benzamide (YSL-109), was assayed on TNBC cell line (MDA-MB231) showing an antiproliferative activity (IC50 = 50.34 ± 1.11 µM), whereas on fibroblast, it was lesser toxic. After corroborating the in vitro antiproliferative activity of YSL-109 in TNBC, the toxicological profile was explored using combined approach with in silico tools and experimental assays. YSL-109 shows moderate mutagenic activity on TA-98 strain at 30 and 100 µM in the Ames test, whereas YSL-109 did not show in vivo genotoxicity and its oral acute toxicity (LD50) in CD-1 female mice was higher than 2000 mg/kg, which is in agreement with our in silico predictions. According to these results, YSL-109 represents an interesting compound to be explored for the treatment of TNBC under preclinical in vivo models.

Development of the ESEx index: a tool for predicting risk of recurrent severe COPD exacerbations.

Background: In chronic obstructive pulmonary disease (COPD), multiple recurrent severe exacerbations that require hospitalization can occur. These events are strongly associated with death and other clinical complications. Objectives: We aimed to develop a prognostic model that could identify patients with COPD that are at risk of multiple recurrent severe exacerbations within 3 years. Design: Prospective cohort. Methods: The derivation cohort comprised patients with stable, moderate-to-severe COPD. Multivariable logistic regression analyses were performed to develop the final model. Based on regression coefficients, a simplified index (ESEx) was established. Both, model and index, were assessed for predictive performance by measuring discrimination and calibration. Results: Over 3 years, 16.4% of patients with COPD experienced at least three severe recurrent exacerbations. The prognostic model showed good discrimination of high-risk patients, based on three characteristics: the number of severe exacerbations in the previous year, performance in the five-repetition sit-to-stand test, and in the 6-minute-walk test. The ESEx index provided good level of discrimination [areas under the receiver operating characteristic curve (AUCs): 0.913]. Conclusions: The ESEx index showed good internal validation for the identification of patients at risk of three recurrent severe COPD exacerbations within 3 years. These tools could be used to identify patients who require early interventions and motivate patients to improve physical performance to prevent recurrent exacerbations.

Effectiveness of an O-Alkyl Hydroxamate in Dogs with Naturally Acquired Canine Leishmaniosis: An Exploratory Clinical Trial.

Canine leishmaniosis is a challenge in veterinary medicine and no drug to date has achieved parasite clearance in dogs. Histone deacetylase inhibitors are a drug class widely used in cancer chemotherapy. We have successfully used O-alkyl hydroxamates (vorinostat derivatives) in the treatment of a laboratory model of visceral leishmaniasis without showing toxicity. In order to test the effectiveness of a particular compound, MTC-305, a parallel-group, randomized, single-centre, exploratory study was designed in naturally infected dogs. In this clinical trial, 18 dogs were allocated into 3 groups and were treated with either meglumine antimoniate (104 mg SbV/kg), MTC-305 (3.75 mg/kg) or a combination of both using a lower MTC-305 dose (1.5 mg/kg) through a subcutaneous route for 2 treatment courses of 30 days, separated by a 30-day rest period. After treatment, a follow-up time of 4 months was established. Parasite burden in bone marrow, lymph node and peripheral blood were quantified through qPCR. Antibody titres were determined through an immunofluorescence antibody test, and cytokine expression values were calculated through RT-qPCR. Treatment safety was evaluated through the assessment of haematological and biochemical parameters in blood, weight, and gastrointestinal alterations. Assessment was carried out before, between and after treatment series. Treatment with MTC-305 was effective at reducing parasite burdens and improving the animals' clinical picture. Dogs treated with this compound did not present significant toxicity signs. These results were superior to those obtained using the reference drug, meglumine antimoniate, in monotherapy. These results would support a broader clinical trial, optimised dosage, and an expanded follow-up stage to confirm the efficacy of this drug.

In vitro bacteriological effect of tri-beveled needle electrolysis against Staphylococcus aureus.

Percutaneous needle electrolysis using tri-beveled needles with a specific protocol (5 mA applied for 25 s) has demonstrated to provoke a clinical reduction of recurrent bacterial infections in mammary fistulas. However, the bactericidal effect of needle electrolysis in this pathology remains theoretical. This in vitro study evaluated the bactericidal effect of this protocol and whether it changed when introducing small variations. Staphylococcus aureus were generated in saline solution (9 Log10 CFU/mL) and treated in three different experiments including the main protocol and introducing variations in needle gauge, intensity, and total dosage, respectively. After 24 h, the viable cell count showed that the protocol had an average reduction of 5 log10 CFU/ml compared to the control group. While variations in needle gauge did not modify this effect, variations in current intensity or dosage did. This study demonstrated that the bacterial effect was greater by increasing either current intensity or total dosage, and it decreased with substantial reductions of these parameters.

Galvanic current activates the NLRP3 inflammasome to promote Type I collagen production in tendon.

The NLRP3 inflammasome coordinates inflammation in response to different pathogen- and damage-associated molecular patterns, being implicated in different infectious, chronic inflammatory, metabolic and degenerative diseases. In chronic tendinopathic lesions, different non-resolving mechanisms produce a degenerative condition that impairs tissue healing and which therefore complicates their clinical management. Percutaneous needle electrolysis consists of the application of a galvanic current and is an emerging treatment for tendinopathies. In the present study, we found that galvanic current activates the NLRP3 inflammasome and induces an inflammatory response that promotes a collagen-mediated regeneration of the tendon in mice. This study establishes the molecular mechanism of percutaneous electrolysis that can be used to treat chronic lesions and describes the beneficial effects of an induced inflammasome-related response.

Targeting Several Biologically Reported Targets of Glioblastoma Multiforme by Assaying 2D and 3D Cultured Cells.

Glioblastoma multiforme (GBM) is account for 70% of all primary malignancies of the central nervous system. The median survival of human patients after treatment is around 15 months. There are several biological targets which have been reported that can be pursued using ligands with varied structures to treat this disease. In our group, we have developed several ligands that target a wide range of proteins involved in anticancer effects, such as histone deacetylase (HDACs), G protein-coupled estrogen receptor 1 (GPER), estrogen receptor-beta (ERß) and NADPH oxidase (NOX), that were screened on bidimensional (2D) and tridimensional (3D) GBM stem cells like (GSC). Our results show that some HDAC inhibitors show antiproliferative properties at 21-32 µM. These results suggest that in this 3D culture, HDACs could be the most relevant targets that are modulated to induce the antiproliferative effects that require in the future further experimental studies.

In silico design of HDAC6 inhibitors with neuroprotective effects.

HDAC6 has emerged as a molecular target to treat neurodegenerative disorders, due to its participation in protein aggregate degradation, oxidative stress process, mitochondrial transport, and axonal transport. Thus, in this work we have designed a set of 485 compounds with hydroxamic and bulky-hydrophobic moieties that may function as HDAC6 inhibitors with a neuroprotective effect. These compounds were filtered by their predicted ADMET properties and their affinity to HDAC6 demonstrated by molecular docking and molecular dynamics simulations. The combination of in silico with in vitro neuroprotective results allowed the identification of a lead compound (FH-27) which shows neuroprotective effect that could be due to HDAC6 inhibition. Further, FH-27 chemical moiety was used to design a second series of compounds improving the neuroprotective effect from 2- to 10-fold higher (YSL-99, YSL-109, YSL-112, YSL-116 and YSL-121; 1.25 ± 0.67, 1.82 ± 1.06, 7.52 ± 1.78, 5.59 and 5.62 ± 0.31 µM, respectively). In addition, the R enantiomer of FH-27 (YSL-106) was synthesized, showing a better neuroprotective effect (1.27 ± 0.60 µM). In conclusion, we accomplish the in silico design, synthesis, and biological evaluation of hydroxamic acid derivatives with neuroprotective effect as suggested by an in vitro model. Communicated by Ramaswamy H. Sarma.

Galvanic current dosage and bacterial concentration are determinants of the bactericidal effect of percutaneous needle electrolysis: an in vitro study.

Percutaneous needle electrolysis (PNE) is a physiotherapy technique that has been shown to be effective in different pathologies such as tendinopathies or mammary fistula. For many years, theoretical bactericidal and germicidal effects have been attributed to this type of galvanic currents, partly explained by the changes in pH that it generates. However, these effects have not yet been demonstrated. The aim of this study was to evaluate the bactericidal effect and the changes in pH caused by PNE. S. aureus were prepared in two different solutions (TSB and saline solution) and in different concentrations (from 9 to 6 Log10 CFU/mL). Bacteria were treated with three experimental PNE doses to assess bacterial death levels and the changes caused to the pH of the medium. The viable cell count showed that all experimental PNE doses had a bactericidal effect against a high concentration (9 Log10 CFU/mL) of S. aureus in saline solution (p < 0.001). Furthermore, we found that when the concentration of bacteria decreased, a lower dose of galvanic current generated the same effect as a higher dose. Changes in pH were registered only in experiments performed with saline solution. PNE had a bactericidal effect against S. aureus and the level of this effect was mainly modulated by the solution, the bacterial concentration and the dose. Changes affecting pH were modulated by the type of solution and there was no relationship between this and bacterial death.

Modifications on the Tetrahydroquinoline Scaffold Targeting a Phenylalanine Cluster on GPER as Antiproliferative Compounds against Renal, Liver and Pancreatic Cancer Cells.

The implementation of chemo- and bioinformatics tools is a crucial step in the design of structure-based drugs, enabling the identification of more specific and effective molecules against cancer without side effects. In this study, three new compounds were designed and synthesized with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-tox) properties and high affinity for the G protein-coupled estrogen receptor (GPER) binding site by in silico methods, which correlated with the growth inhibitory activity tested in a cluster of cancer cell lines. Docking and molecular dynamics (MD) simulations accompanied by a molecular mechanics/generalized Born surface area (MMGBSA) approach yielded the binding modes and energetic features of the proposed compounds on GPER. These in silico studies showed that the compounds reached the GPER binding site, establishing interactions with a phenylalanine cluster (F206, F208 and F278) required for GPER molecular recognition of its agonist and antagonist ligands. Finally, a 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay showed growth inhibitory activity of compounds 4, 5 and 7 in three different cancer cell lines-MIA Paca-2, RCC4-VA and Hep G2-at micromolar concentrations. These new molecules with specific chemical modifications of the GPER pharmacophore open up the possibility of generating new compounds capable of reaching the GPER binding site with potential growth inhibitory activities against nonconventional GPER cell models.

Small Molecule-Based Enzyme Inhibitors in the Treatment of Primary Hyperoxalurias.

Primary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism. PHs classification based on gene mutations parallel a variety of enzymatic defects, and all involve the harmful accumulation of calcium oxalate crystals that produce systemic damage. These geographically widespread rare diseases have a deep impact in the life quality of the patients. Until recently, treatments were limited to palliative measures and kidney/liver transplants in the most severe forms. Efforts made to develop pharmacological treatments succeeded with the biotechnological agent lumasiran, a siRNA product against glycolate oxidase, which has become the first effective therapy to treat PH1. However, small molecule drugs have classically been preferred since they benefit from experience and have better pharmacological properties. The development of small molecule inhibitors designed against key enzymes of glyoxylate metabolism is on the focus of research. Enzyme inhibitors are successful and widely used in several diseases and their pharmacokinetic advantages are well known. In PHs, effective enzymatic targets have been determined and characterized for drug design and interesting inhibitory activities have been achieved both in vitro and in vivo. This review describes the most recent advances towards the development of small molecule enzyme inhibitors in the treatment of PHs, introducing the multi-target approach as a more effective and safe therapeutic option.

Influence of Acromial Morphologic Characteristics and Acromioclavicular Arthrosis on the Effect of Platelet-Rich Plasma on Partial Tears of the Supraspinatus Tendon.

OBJECTIVE. The purposes of this study were to determine the medium-term effect of ultrasound-guided infiltration of platelet-rich plasma (PRP) on partial tears of the supraspinatus tendon (SST) and to identify prognostic indicators of an unfavorable outcome. SUBJECTS AND METHODS. Over a period of 4 years, patients with a partial SST tear smaller than 1.5 cm referred for ultrasound-guided PRP infiltration (1 mL) for shoulder pain lasting more than 3 months were recruited consecutively. MRI was used to analyze the type of acromion and presence of acromioclavicular (AC) arthrosis. Primary (size of the tear and associated bursitis) and secondary (mobility and pain) results were collected at 3 months. RESULTS. The study included 128 patients (66 men, 62 women; mean age, 48.3 years; range, 20-59 years). At 3 months, favorable evolution of the tear repair was recorded in 71.1% (91/128) of patients and resolution of bursitis in 66.7% (42/63). Changes in tear size had large effect sizes (Cohen d ≥ 1.16), as did pain and shoulder mobility (Cohen d ≥ 0.95). The strongest predictors of unfavorable evolution of tear and bursitis were type 3 acromion and types 1 and 2 acromion with AC arthrosis (p < 0.001; ß = 20.412). CONCLUSION. Ultrasound-guided PRP infiltration of partial tears of the SST relieves pain and improves shoulder mobility, but its effect on the size of the tear is influenced by the morphologic characteristics of the acromion and the presence of AC arthrosis. The effect of PRP is insufficient in patients with a type 3 acromion or severe AC arthrosis.

Therapeutic pulmonary telerehabilitation protocol for patients affected by COVID-19, confined to their homes: study protocol for a randomized controlled trial.

BACKGROUND: In December 2019, 27 cases of pneumonia, of unknown cause, were identified in the province of Hubei (China). The WHO declared the situation as a Public Health Emergency of International Concern, and it was finally declared a global pandemic on March 11, 2020. The Spanish Government obliges the entire population to remain confined to their homes, with the exception of essential basic services, to stop the spread of COVID-19. Home isolation implies a notable physical deconditioning. Telerehabilitation methods have reported positive experiences, and we propose to study in affected patients of COVID-19, due to the general house confinement of the entire Spanish population. METHODS: Patients will be recruited in the regions of Andalusia, Murcia, and Valencia (Spain). Patients will remain confined to their homes, and there, they will carry out their assigned exercise program, which will be controlled telematically. Evaluators will attend to carry out all measurements at the beginning, during, and end of the study, telematically controlled. The patients will be randomly divided into three groups, two of them will perform a home exercise program (breathing exercises or non-specific exercises for muscle toning) and the third group will perform sedentary activities, using mental activation techniques, and will act as a sham group. We will evaluate respiratory variables and other variables of the physical state through physical tests, effort, and perceived fatigue. The data will be statistically analyzed, and the hypotheses will be tested between the groups, using the SPSS software, v.24, considering a 95% confidence interval. DISCUSSION: We will analyze the results, in terms of the level of fatigue and perceived exertion, physical health, and maintenance of respiratory activity of two types of exercise programs, toning and respiratory, applied in patients affected by COVID-19 during the period of home confinement. We intend to investigate a field not previously studied, such as the repercussion of carrying out a toning and respiratory exercise program in these patients, in historical circumstances that no one had previously observed in Spain, since the general population has never been forced to remain confined in their homes, due to a pandemic infection, by a coronavirus (COVID-19). Observing the effects that these two home exercise programs could produce in patients infected with COVID-19, we will try to better analyze and understand the mechanisms that are associated with the worsening of breathing in this type of patient. TRIAL REGISTRATION: Brazilian Clinical Trial Registry RBR-6m69fc . Registered on March 31, 2020.

Hydroxamic acid derivatives as HDAC1, HDAC6 and HDAC8 inhibitors with antiproliferative activity in cancer cell lines.

Histone deacetylases (HDACs) belong to a family of enzymes that remove acetyl groups from the ɛ-amino of histone and nonhistone proteins. Additionally, HDACs participate in the genesis and development of cancer diseases as promising therapeutic targets to treat cancer. Therefore, in this work, we designed and evaluated a set of hydroxamic acid derivatives that contain a hydrophobic moiety as antiproliferative HDAC inhibitors. For the chemical structure design, in silico tools (molecular docking, molecular dynamic (MD) simulations, ADME/Tox properties were used to target Zn2+ atoms and HDAC hydrophobic cavities. The most promising compounds were assayed in different cancer cell lines, including hepatocellular carcinoma (HepG2), pancreatic cancer (MIA PaCa-2), breast cancer (MCF-7 and HCC1954), renal cancer (RCC4-VHL and RCC4-VA) and neuroblastoma (SH-SY5Y). Molecular docking and MD simulations coupled to the MMGBSA approach showed that the target compounds have affinity for HDAC1, HDAC6 and HDAC8. Of all the compounds evaluated, YSL-109 showed the best activity against hepatocellular carcinoma (HepG2 cell line, IC50 = 3.39 µM), breast cancer (MCF-7 cell line, IC50 = 3.41 µM; HCC1954 cell line, IC50 = 3.41 µM) and neuroblastoma (SH-SY5Y cell line, IC50 = 6.42 µM). In vitro inhibition assays of compound YSL-109 against the HDACs showed IC50 values of 259.439 µM for HDAC1, 0.537 nM for HDAC6 and 2.24 µM for HDAC8.

Patterns and predictors of low physical activity in patients with stable COPD: a longitudinal study.

BACKGROUND: Despite the frequency and negative impact of low physical activity among patients with chronic obstructive pulmonary disease (COPD), little is known about how it persists and remits over time or the factors predicting new states of low physical activity. The aim of the study was to determine the probability of a transition between states of low and nonlow physical activity in a cohort of patients with stable COPD followed for 2 years. We also investigated different potentially modifiable factors to determine whether they can predict new states of low physical activity. METHODS: We prospectively included 137 patients with stable COPD (mean age 66.9 ± 8.3 years). Physical activity was measured at baseline and at 1 and 2 years of follow up. Low physical activity was defined according to energy expenditure by cut-off points from the Fried frailty model. The likelihood of annual transition towards new states and recovery was calculated. We evaluated demographic, frailty, nonrespiratory, and respiratory variables as potential predictors, using generalized estimating equations. RESULTS: At baseline, 37 patients (27%) presented with low physical activity. During the study period, a total of 179 annual transitions were identified with nonlow physical activity at the beginning of the year; 17.5% transitioned to low physical activity. In contrast, 34.3% of the 67 transitions that started with low physical activity recovered. Predictors of transition to new states of low physical activity were dyspnea ⩾2 (odds ratio = 3.21; 95% confidence interval: 1.20-8.61) and poor performance on the five sit-to-stand test (odds ratio = 4.75; 95% confidence interval: 1.30-17.47). CONCLUSIONS: The change between levels of low and nonlow physical activity is dynamic, especially for recovery. Annual transitions toward new states of low physical activity are likely among patients with dyspnea or poor performance on the five sit-to-stand test. The reviews of this paper are available via the supplemental material section.

Frailty transitions and associated clinical outcomes in patients with stable COPD: A longitudinal study.

BACKGROUND: Although frailty is a frequent occurrence in chronic obstructive pulmonary disease (COPD) patients, evidence on the frequency of frailty transition is scarce. AIMS: The present study aimed to describe the frailty status transition rates over a 2-year period and their associated clinical outcomes in stable COPD patients, and to determine predictors of improvement in frailty status. METHODS: We prospectively included 119 patients with stable COPD (mean age ± SD, 66.9 ± 7.9 years) over a follow-up period of 2 years. Frailty was assessed using the Fried criteria (unintentional weight loss, weakness, exhaustion, low activity level, and slow walking speed). Several demographic, clinical, and health-related variables were measured. We calculated the rates for each of the frailty transitions (no change, improvement, or worsening) between baseline and 2 years. Outcomes were compared using one-way analysis of variance and predictors of improvement were identified in multivariate logistic regression. RESULTS: After 2 years of follow-up, 21 (17.6%) patients had an improved frailty status, 14 (11.7%) had worsened, and 84 (70.5%) had maintained the same frailty status. The worsening group (vs no change group) had greater dyspnea (p = 0.013) and disability (p = 0.036) and lower handgrip strength (p = 0.001). In contrast, the improved group (vs no change group) had greater handgrip (p<0.001) and quadriceps strength (p = 0.032). Furthermore, the improved group had greater handgrip strength (p<0.001), quadriceps strength (p = 0.003), physical activity (p = 0.008), and lower disability (p = 0.019) than the worsening group. Additionally, we determined that the 5STS test (≤ 13.6s) and exacerbations (≥ 2) were independent predictors for improvement in frailty status [adjusted OR 9.46, p = 0.058 and adjusted OR 0.12, p = 0.026, respectively]. CONCLUSIONS: Frailty is a dynamic process for approximately one-third of patients with stable COPD and transitions in frailty status are associated with significant changes in clinical outcomes. The 5STS and exacerbations were independent predictors of improvement in frailty status.

Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry.

OBJECTIVES: This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. METHODS: RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. RESULTS: Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. CONCLUSION: Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies.

Clinical relevance of monitoring serum adalimumab levels in axial spondyloarthritis.

Our aim was to assess the relationship between serum adalimumab levels, anti-drug antibodies (ADA) and disease activity in patients with axial spondylarthritis (SpA). We have carried out a single-centre cross-sectional study. adalimumab and ADA levels were analysed with ELISA and correlated with SpA activity using BASDAI and ASDAS scores. Adalimumab cut-off value was calculated to discriminate inactive disease/low disease activity (BASDAI < 4; ASDAS < 2.1) from moderate/high disease activity (BASDAI ≥ 4; ASDAS ≥ 2.1), using a receiver operating characteristic (ROC) curve. Up to January 2016, 51 consecutive patients were included. The median (range) age was 46.6 (18-68) and 47.1% were women. ADA prevalence was 27.5%, with none detected in the 21.6% receiving concomitant disease-modifying antirheumatic drugs (DMARDs) (p = 0.021). Adalimumab level was normal (> 3 mg/l) in 36 patients (70.6%), all without ADA. Fifteen patients (29.4%) had subtherapeutic adalimumab levels (< 3 mg/l), with ADA in 14 (93%). Median adalimumab (mg/l) was significantly higher in patients with inactive disease/low disease activity: BASDAI < 4 vs ≥ 4: 9.5 vs 2.6 (p < 0.01); ASDAS-CRP < 2.1 vs ≥ 2.1: 9.3 vs 0.3 (p < 0.001); ASDAS-ESR < 2.1 vs ≥ 2.1: 9.9 vs 3.0 (p < 0.001), and this finding was consistent with the result of the multivariate model. Patients with inactive disease/low disease activity presented significantly lower ADA levels. The adalimumab level cut-offs and area under the curve (AUC) obtained in the ROC curves were: ASDAS-CRP (< 2.1) 4.6 mg/l (AUC 81.2%; 95% CI 67.5-94.9; p < 0.001); ASDAS-ESR (< 2.1) 7.7 mg/l (AUC 82.4%; 95% CI 69.3-95.5; p < 0.001); BASDAI (< 4) 6.4 mg/l (AUC 73.5%; 95% CI 58.6-88.3; p < 0.01). In conclusion, presence of ADA in axial SpA patients treated with adalimumab was associated with lower serum drug levels. ADA levels were lower and adalimumab levels were higher in patients with inactive disease/low disease activity based on BASDAI and ASDAS indices. Concomitant treatment with MTX reduces de likelihood of finding ADA. Serum adalimumab levels above 4.6 mg/l are recommended to avoid compromising efficacy.