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1.
Nat Prod Res ; : 1-4, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38164692

ABSTRACT

The essential oil from Lippia origanoides (EOLO) is employed in traditional medicine as it has both antimicrobial and anti-inflammatory properties. The current investigation first evaluated the EOLO's cytotoxic activity in tumour (SiHa and HT-29) and non-tumour (human lymphocyte) cells by MTT. The effect on ROS production was further evaluated in cancer cells by fluorimetry. The oil's mutagenic and antifungal activities were also evaluated using, respectively, the in vitro micronucleus test and the broth microdilution method. The EOLO displayed significant cytotoxicity in both cancer cell lines, with IC50 values of 20.2 µg/mL and 24.3 µg/mL for HT-29 and for SiHa cell lines, respectively. EOLO increased ROS production, was unable to raise the micronucleus frequencies and significantly reduced the cytokinesis block proliferation indices, revealing its anti-proliferative action. The results demonstrate that EOLO is devoid of mutagenic activity but possesses significant activity against tumour and non-tumour human cells, reinforcing its biological potential.

2.
Article in English | MEDLINE | ID: mdl-37998293

ABSTRACT

The Health Assessment Questionnaire Disability Index (HAQ-DI) was completed with five visual analog scales to assess systemic sclerosis (SSc) called Scleroderma HAQ (SHAQ). We performed a validation of the European Portuguese version of SHAQ for patients with SSc. Patients with different forms of SSc from five Hospital Centers were invited. The reliability of the Portuguese SHAQ was evaluated by internal consistency and by test-retest reliability. Content validity was checked by two rheumatologists and by a panel of patients. Construct validity was assessed by structural validity and by known-groups hypothesis tests. Criterion validity was addressed with selected dimensions from the UCLA GIT 2.0, the SF-36v2, and the EuroQoL EQ-5D-5L. A total of 102 SSc patients agreed to participate, 31 of which answered to the retest. HAQ-DI demonstrated high internal consistency reliability (α = 0.866) and SHAQ also showed high test-retest reliability (ICC 0.61-0.95). We evidenced the unidimensionality of all VASs. HAQ-DI scores were worse in males, patients older than 65 years, and individuals with a diffuse form of SSc. Criterion validity was mainly evidenced through the correlation between the HAQ-DI and SF-36v2 physical summary measure (r = -0.688) and EQ-5D-5L index score (r = -0.723). Likewise, the SHAQ overall disease severity VAS was also correlated with SF-36v2 physical summary measure (r = -0.628). Mental score correlations were smaller. With the exception of the Raynaud's VAS, all the other VASs correlated well with similar clinical variables. This paper provides evidence to demonstrate how reliable and valid the European Portuguese version of SHAQ is, to be used in SSc patients to assess the clinical severity under the perspective of patients.


Subject(s)
Scleroderma, Systemic , Male , Humans , Reproducibility of Results , Portugal , Surveys and Questionnaires , Severity of Illness Index , Scleroderma, Systemic/diagnosis , Quality of Life , Disability Evaluation
3.
J Chem Inf Model ; 63(15): 4888-4899, 2023 08 14.
Article in English | MEDLINE | ID: mdl-37504578

ABSTRACT

hERG is a voltage-gated potassium channel involved in the heart contraction whose defections are associated with the cardiac arrhythmia Long QT Syndrome type 2. The activator RPR260243 (RPR) represents a possible candidate to pharmacologically treat LQTS2 because it enhances the opening of the channel. However, the molecular detail of its action mechanism remains quite elusive. Here, we address the problem using a combination of docking, molecular dynamics simulations, and network analysis. We show that the drug preferably binds at the interface between the voltage sensor and the pore, enhancing the canonical activation path and determining a whole-structure rearrangement of the channel that slightly impairs inactivation.


Subject(s)
Ether-A-Go-Go Potassium Channels , Heart , Humans , Ether-A-Go-Go Potassium Channels/metabolism , Piperidines , Arrhythmias, Cardiac/drug therapy , ERG1 Potassium Channel
4.
Clin Rheumatol ; 42(8): 2125-2134, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37154983

ABSTRACT

INTRODUCTION/OBJECTIVES: The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis. METHOD: A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed. RESULTS: We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02-6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28-9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2-14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7-34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001-0477, p = 0.015). CONCLUSIONS: Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors' variability. Key Points • Prevalence of subclinical calcinosis in SSc patients is substantial. • Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method. • Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis. • Anti-nuclear antibody positivity may be a protective factor for knee calcinosis.


Subject(s)
Calcinosis , Osteoporosis , Scleroderma, Systemic , Female , Humans , Cross-Sectional Studies , Portugal , Calcinosis/complications , Calcinosis/diagnostic imaging , Osteoporosis/complications
6.
Nat Commun ; 14(1): 1110, 2023 02 27.
Article in English | MEDLINE | ID: mdl-36849440

ABSTRACT

Voltage-gated potassium channels are involved in many physiological processes such as nerve impulse transmission, the heartbeat, and muscle contraction. However, for many of them the molecular determinants of the gating mechanism remain elusive. Here, using a combination of theoretical and experimental approaches, we address this problem focusing on the cardiac hERG potassium channel. Network analysis of molecular dynamics trajectories reveals the presence of a kinematic chain of residues that couples the voltage sensor domain to the pore domain and involves the S4/S1 and S1/S5 subunit interfaces. Mutagenesis experiments confirm the role of these residues and interfaces in the activation and inactivation mechanisms. Our findings demonstrate the presence of an electromechanical transduction path crucial for the non-domain-swapped hERG channel gating that resembles the noncanonical path identified in domain-swapped K+ channels.


Subject(s)
Muscle Contraction , Potassium Channels, Voltage-Gated , Heart Rate , Mutagenesis , Synaptic Transmission
7.
Article in English | MEDLINE | ID: mdl-36674306

ABSTRACT

(1) Background: The UCLA GIT 2.0 questionnaire has been recognized as a feasible and reliable instrument to assess gastrointestinal (GI) symptoms in systemic sclerosis (SSc) patients and their impact on quality of life. The aim of this study was to create and validate UCLA GIT 2.0 for Portuguese patients with SSc. (2) Methods: A multi-center study was conducted enrolling SSc patients. UCLA GIT 2.0 was validated in Portuguese using reliability (internal consistency, item -total correlation, and reproducibility) and validity (content, construct, and criterion) tests. Criterion tests included EQ-5D and SF-36v2. Social-demographic and clinical data were collected. (3) Results: 102 SSc patients were included, 82.4% of them female, and with a mean sample age of 57.0 ± 12.5 years old. The limited form of SSc was present in 62% of the patients and 56.9% had fewer than five years of disease duration. Almost 60% presented with SSc-GI involvement with a negative impact on quality of life. The means for SF-36v2 were 39.3 ± 10.3 in the physical component summary and 47.5 ± 12.1 in the mental component summary. Total GI score, reported as mild in 57.8% of the patients, was highly reliable (ICC = 0.912) and the Cronbach's alpha was 0.954. There was a high correlation between the total GI score and EQ-5D-5L and SF-36v2 scores. (4) Conclusion: The Portuguese version of UCLA GIT 2.0 showed good psychometric properties and can be used in research and clinical practice.


Subject(s)
Gastrointestinal Diseases , Scleroderma, Systemic , Humans , Female , Adult , Middle Aged , Aged , Quality of Life , Reproducibility of Results , Portugal , Severity of Illness Index , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/epidemiology , Scleroderma, Systemic/diagnosis , Psychometrics , Surveys and Questionnaires
8.
Clin Exp Rheumatol ; 41(3): 704-710, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35930489

ABSTRACT

OBJECTIVES: Patient centred care is an increasingly important paradigm. Applying a treat-to-target strategy to the impact of the disease in patients' lives seems a very promising tool to serve this purpose. We aimed to evaluate if maximum acceptable impact scores (target-values) defined at the population level provide an appropriate representation for most individual patients. To determine if the individually established target values of impact are consistent enough to be used in a treat-to-target strategy. METHODS: Consecutive patients with rheumatoid arthritis were asked to indicate, in two consecutive visits, the maximum severity of impact they considered acceptable to live with for the rest of their lives, in the seven domains of Rheumatoid Arthritis Impact of Disease score. The individual adequacy of population-based reference values was assessed by measures of dispersion. Stability of individual target-values were evaluated through intraclass correlation coefficient. Socio-demographic, clinical and psychological features were tested as co-factors of stability. RESULTS: 299 patients were included. The dispersion of targets was wide (CV>0.68), thus limiting the use of any population-based single values as targets for the individual patients. Although the mean target values were very similar in both visits for all domains, reliability was poor in all cases (ICCs: 0.37-0.47). Only 25-30% of the patients selected the same target value in the 2 visits. No explanatory factors for (non-)stability were identified. CONCLUSIONS: Quantified impact targets defined at population level are not appropriate for individual patient care. Research on alternative tools to support patient-centred, target-oriented management strategies is warranted.


Subject(s)
Arthritis, Rheumatoid , Humans , Reproducibility of Results , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/therapy , Arthritis, Rheumatoid/psychology
10.
Waste Manag ; 154: 320-330, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36326542

ABSTRACT

This study aims to identify the main causes of food waste (especially fruit and vegetables) and their relationship with prevention practices at supermarket and supplier levels. To do so, we conducted case studies in four Brazilian supermarket chains and their suppliers. Our findings show that although supermarkets seem to be concerned about avoiding food waste, they mostly focus on internal prevention actions, reflecting the lack of collaboration and information between supermarkets and suppliers. The low investment of supermarkets in actions to prevent food waste is focused only on their internal operations and, despite this, training is inefficient due to the high level of staff turnover and lack of involvement of suppliers in participating in this training. The use of technologies such as packaging, traceability, refrigeration, and transport equipment is insufficient, it increases production costs. A lack of strict legislation in Brazil makes it difficult for supermarkets and suppliers to donate food. Cultural issues specific to Brazil, such as consumer overhandling fruit and vegetables before buying these products, generate a great deal of waste. The paper contributes to the literature by identifying the main root causes of food waste and providing a list of prevention practices that supermarkets and suppliers can benefit from. Managerially, it can help supermarket managers spot the causes of food waste within their operations, and hence change, improve or implement practices and behavior to prevent food waste.

11.
ARP Rheumatol ; 1(ARP Rheumatology, nº3 2022): 197-204, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36056937

ABSTRACT

OBJECTIVES: Salivary glands ultrasonography has recently been shown to be useful in the diagnosis of Primary Sjögren's Syndrome (pSS). Shear-wave elastography (SWE) is a promising tool for the quantitative assessment of tissues stiffness, but studies evaluating its role in pSS diagnosis are limited. This study aimed at investigating the diagnostic performance of SWE in pSS. MATERIALS AND METHODS: Cross-sectional study including patients fulfilling the 2016 ACR/EULAR classification criteria for pSS and healthy subjects. The four major salivary glands were assessed using SGUS. B-mode scans were rated using the Hocevar score, and shear-wave velocity (SWV) values were obtained using SWE. Intraclass-correlation coefficient (ICC) estimates were used to assess reliability. Cut-off values for differentiating pSS patients from healthy subjects were calculated using Receiver-Operating Characteristics (ROC) curves. RESULTS: We included 50 pSS and 25 healthy subjects. Inter-rater reliability of SWE was moderate (ICC=0.64) and intra-rater reliability was moderate to good (ICC= 0.73 to 0.83). Total SWV (2.09 m/s (0.32); p < 0.001), parotid SWV (2.25 m/s (0.40)) and submandibular SWV (1.92 m/s (0.38)) were significantly higher in pSS patients. Total and parotid SWV presented good diagnostic performance for pSS diagnosis (AUROC= 0.80 and 0.81, respectively). The Hocevar score demonstrated excellent diagnostic performance (AUROC= 0.98) and combining it with total SWV did not result in statistically significant improvement (p=0.301). CONCLUSIONS: SWE may contribute to the diagnosis of pSS. Large prospective studies including sicca and secondary SS patients, as well as the standardisation of SWE protocols, are warranted to assess the role of SWE in pSS management.


Subject(s)
Elasticity Imaging Techniques , Sjogren's Syndrome , Humans , Sjogren's Syndrome/diagnosis , Elasticity Imaging Techniques/methods , Cross-Sectional Studies , Prospective Studies , Reproducibility of Results , Salivary Glands/diagnostic imaging
12.
Heliyon ; 8(4): e09257, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35497045

ABSTRACT

This report estimated the loss of life and the variation of risk level to people and properties from the city of São José do Jacuípe, at Bahia State, in Brazil, through a simulation of the dam break near the city. The simulations employ the HEC-RAS program with the HEC-GeoRAS plugin, both made available by the U.S. Army Corps of Engineers. The program is a hydrological model for the hydric flow propagation arising from the complete resolution of the Saint-Venant equation, while the plugin was used for vector editing by creating a geomorphological model from the river basin. The results from the research demonstrated that the city is exposed to a risk that is time dependent. In addition, the lack of a warning system about a possible break could cause the death of almost all residents. Otherwise, with a warning system operating, the estimation of destruction would be dramatically reduced.

13.
Molecules ; 27(10)2022 May 10.
Article in English | MEDLINE | ID: mdl-35630535

ABSTRACT

Biomineral formation is a common trait and prominent for soil Actinobacteria, including the genus Streptomyces. We investigated the formation of nickel-containing biominerals in the presence of a heavy-metal-resistant Streptomyces mirabilis P16B-1. Biomineralization was found to occur both in solid and liquid media. Minerals were identified with Raman spectroscopy and TEM-EDX to be either Mg-containing struvite produced in media containing no nickel, or Ni-struvite where Ni replaces the Mg when nickel was present in sufficient concentrations in the media. The precipitation of Ni-struvite reduced the concentration of nickel available in the medium. Therefore, Ni-struvite precipitation is an efficient mechanism for tolerance to nickel. We discuss the contribution of a plasmid-encoded nickel efflux transporter in aiding biomineralization. In the elevated local concentrations of Ni surrounding the cells carrying this plasmid, more biominerals occurred supporting this point of view. The biominerals formed have been quantified, showing that the conditions of growth do influence mineralization. This control is also visible in differences observed to biosynthetically synthesized Ni-struvites, including the use of sterile-filtered culture supernatant. The use of the wildtype S. mirabilis P16B-1 and its plasmid-free derivative, as well as a metal-sensitive recipient, S. lividans, and the same transformed with the plasmid, allowed us to access genetic factors involved in this partial control of biomineral formation.


Subject(s)
Metals, Heavy , Streptomyces , Biomineralization , Nickel/chemistry , Streptomyces/genetics , Struvite
14.
Commun Biol ; 5(1): 165, 2022 02 24.
Article in English | MEDLINE | ID: mdl-35210539

ABSTRACT

The elusive activation/deactivation mechanism of hERG is investigated, a voltage-gated potassium channel involved in severe inherited and drug-induced cardiac channelopathies, including the Long QT Syndrome. Firstly, the available structural data are integrated by providing a homology model for the closed state of the channel. Secondly, molecular dynamics combined with a network analysis revealed two distinct pathways coupling the voltage sensor domain with the pore domain. Interestingly, some LQTS-related mutations known to impair the activation/deactivation mechanism are distributed along the identified pathways, which thus suggests a microscopic interpretation of their role. Split channels simulations clarify a surprising feature of this channel, which is still able to gate when a cut is introduced between the voltage sensor domain and the neighboring helix S5. In summary, the presented results suggest possible activation/deactivation mechanisms of non-domain-swapped potassium channels that may aid in biomedical applications.


Subject(s)
Ether-A-Go-Go Potassium Channels , Molecular Dynamics Simulation , ERG1 Potassium Channel/chemistry , ERG1 Potassium Channel/genetics , ERG1 Potassium Channel/metabolism , Ether-A-Go-Go Potassium Channels/chemistry , Ether-A-Go-Go Potassium Channels/genetics , Ether-A-Go-Go Potassium Channels/metabolism , Ion Channel Gating , Mutation
15.
Arthritis Care Res (Hoboken) ; 74(10): 1723-1735, 2022 10.
Article in English | MEDLINE | ID: mdl-33973383

ABSTRACT

OBJECTIVE: To gauge the evidence of periodontal therapy's impact on measures of disease activity and systemic inflammatory burden in individuals with rheumatoid arthritis (RA). METHODS: A search for randomized trials and controlled cohort studies of RA patients with periodontitis was conducted on April 7, 2019, with an update on December 17, 2020 in PubMed, Cochrane Library (CENTRAL), Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trial Registry Platform portal. Two reviewers screened titles and abstracts and selected papers for full-text review. We used Outcome Measures in Rheumatology (OMERACT)-endorsed outcome domains for RA trials and summarized continuous outcomes using standardized mean differences (SMDs) with 95% confidence intervals (95% CIs). We evaluated inconsistency using the I2 statistic and combined SMDs using random-effects models for the meta-analyses; fixed-effect meta-analyses were used for sensitivity analysis. To explore heterogeneity, we added stratified/meta-regression analyses, expressed in T2 . RESULTS: Of the 1,909 studies identified, 9 (including 10 comparisons) were eligible for quantitative synthesis (n = 388). Evidence suggested a favorable effect of periodontal treatment on disease activity (SMD -0.88 [95% CI -1.38, -0.38]; n = 311). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to judge the estimates' certainty; evidence rated as having low or very low certainty indicated that any possible effect of periodontal treatment in RA is likely to change as more evidence is provided. Selection bias and RA medication stability were highlighted as sources of heterogeneity between studies. CONCLUSION: There is an urgent need for a well-designed prospective cohort study (preferably a randomized controlled trial) of patients with RA and periodontitis using rigorous protocols, standardized diagnostic criteria, data collection, and adequate duration of follow-up.


Subject(s)
Arthritis, Rheumatoid , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/therapy , Humans , Prospective Studies
16.
Braz J Microbiol ; 52(4): 1825-1833, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34435341

ABSTRACT

Paenibacillus elgii AC13 produces antimicrobial lipopeptides of agricultural and pharmaceutical importance. It secretes four cyclic lipopeptides named pelgipeptins, previously characterized in P. elgii B69. These lipopeptides result from the expression of a nonribosomal peptide gene cluster. P. elgii AC13 also produced two linear lipopeptides with ratios of [M + H] + 1105 and 1119 m/z. These compounds were previously observed in Paenibacillus sp. strain OSY-N, but due to purification difficulties, their characterization was executed using synthetically produced linear pelgipeptins. In the present study, purification was achieved from the supernatants of cultures from three complex media by high-performance liquid chromatography. The partial characterization of linear pelgipeptins revealed the similar antimicrobial activity and cytotoxicity of their synthetically produced counterparts, known as paenipeptins. Cyclic forms were highly stable to changes in pH, temperature, and organic extraction with n-butanol as shown by mass spectrometry (MALDI-TOF); therefore, these steps did not cause the hydrolysis of pelgipeptins. A low-activity thioesterase could also generate the linear isoforms observed; this enzyme catalyzes the cyclization process and is coded in the same gene cluster. Alternatively, the cyclic forms were hydrolyzed by an unknown protease produced during growth in the complex medium used in the present study. Although culture conditions are known to produce pelgipeptins with different yields and amino acid compositions, the occurrence of linear and cyclic forms simultaneously has not yet been reported. A mixture of cyclic and linear pelgipeptins presents a potential advantage of the higher antimicrobial activity of cyclic forms combined with the lower cytotoxicity of linear isoforms.


Subject(s)
Lipopeptides , Paenibacillus , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Anti-Infective Agents/pharmacology , Bacteria/drug effects , Lipopeptides/chemistry , Lipopeptides/genetics , Lipopeptides/isolation & purification , Lipopeptides/pharmacology , Paenibacillus/chemistry , Paenibacillus/genetics
17.
Acta Reumatol Port ; 46(2): 103-109, 2021.
Article in English | MEDLINE | ID: mdl-34226435

ABSTRACT

BACKGROUND: In rheumatoid arthritis (RA), global disease activity is commonly evaluated, from the patient's and the physician's perspective, through a 100mm visual analogue scale (VAS) and plays an important role in the assessment of diseases activity and treatment decisions. Our aim was to determine patient-physician discordance in the assessment of disease activity and to explore its determinants. METHODS: Cross sectional study including RA patients (ACR/EULAR 2010 classification criteria). The discrepancy between patients-physicians (∆PPhGA) was defined as PGA minus PhGA, and a difference > |20mm| was considered as "discordant". Correlation between ∆PPhGA and other variables was assessed through Pearson's correlation and comparison between groups through t-test. Variables with p < 0.05 or considered clinically relevant were included in multivariable linear regression analysis to identify determinants for ∆PPhGA. A p < 0.05 was considered statistically significant. RESULTS: In total, 467 patients with RA were included (81.2% female; mean age 63.9% ± 12.2 years). PGA and PhGA were discordant in 61.7% of the cases. The proportion of concordance increased (p < 0.01) when considering only patients in remission (DAS 28 3V < 2.6). In multivariable analysis (R2adjusted=0.27), VAS-pain-patient (ß 0.74, 95% CI 0.62-0.88, p=0.00) and TJC (ß 0.16, 95% CI 0.45-0.48, p=0.02) remained associated with a higher ∆PPhGA. CONCLUSION: Our study confirmed that a significant discrepancy between patients and physicians in the assessment of global disease activity is frequent in clinical practice, and is probably due to valorization of different parameters by the two groups.


Subject(s)
Arthritis, Rheumatoid , Physicians , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pain , Physician-Patient Relations , Severity of Illness Index
18.
Joint Bone Spine ; 88(6): 105242, 2021 12.
Article in English | MEDLINE | ID: mdl-34166795

ABSTRACT

OBJECTIVES: To assess whether high patient global assessment (PGA) scores by patients with rheumatoid arthritis (RA) otherwise in remission reflect subclinical inflammation. METHODS: Cross-sectional, single-center study, including consecutive RA patients. Remission states were defined based on the ACR/EULAR Boolean definition: 4V-remission (tender and swollen 28-joint counts (TJC28/SJC28), C-reactive protein (CRP), and PGA all≤1), PGA-near-remission (the same, except PGA>1), and non-remission (any of TJC28, SJC28, CRP>1). A blinded expert musculoskeletal ultrasonographer scanned 44 joints, 38 tendon sheaths, 4 bursae on the same day of the clinical evaluation. Each structure was assessed for the presence of Grey Scale synovial hypertrophy (GS) and Power Doppler (PD), both scored using a semi-quantitative scale (0-3 points). The Global OMERACT-EULAR Synovitis Score (GLOESS, 0-132, primary outcome), and a global tenosynovitis/bursitis score (GTBS) were compared between remission states, using non-parametric tests. Different sensitivity analyses comparing GS and PD subscores were performed. RESULTS: In total, 130 patients (mean age 63 years, 86% female, average disease duration 14 years) were included 40 being in 4V-remission, 40 in PGA-near-remission, 50 in non-remission. 4v-remission and PGA-near-remission presented similar median (IQR) GLOESS, [6 (5-11) and 4 (1-7), P>0.05, respectively] and GTBS [0 (0-1) and 0 (0-2), P>0.05, respectively]. The same was observed in GS, PD scores, and in global synovitis score considering only the 16 joints not included in 28-joint counts. These observations were confirmed in patients with≤5 years disease duration. CONCLUSIONS: Subclinical inflammation is not present among persons with elevated PGA who are otherwise in remission. PGA-near-remission patients would be exposed to the risk of overtreatment if current treatment recommendations were strictly followed. This study supports the need to reconsider the role of PGA in definitions used to target immunosuppressive therapy and to provide a separate and enhanced focus to the patient's experience of the disease.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Synovitis , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/drug therapy , Cross-Sectional Studies , Female , Humans , Inflammation/diagnostic imaging , Inflammation/drug therapy , Male , Middle Aged , Remission Induction , Severity of Illness Index , Synovitis/diagnostic imaging , Synovitis/drug therapy
19.
Rev Assoc Med Bras (1992) ; 67(1): 7-18, 2021 Jan.
Article in English | MEDLINE | ID: mdl-34161478

ABSTRACT

OBJECTIVE: Several prospective randomized trials have shown that hypofractionation has the same efficacy and safety as the conventional fractionation in the treatment of localized prostate cancer. There are many benefits of hypofractionation, including a more convenient schedule for the patients and better use of resources, which is especially important in low- and middle-income countries like Brasil. Based on these data, the Brazilian Society of Radiotherapy (Sociedade Brasileira de Radioterapia) organized this consensus to guide and support the use of hypofractionated radiotherapy for localized prostate cancer in Brasil. METHODS: The relevant literature regarding moderate hypofractionation (mHypo) and ultra-hypofractionation (uHypo) was reviewed and discussed by a group of experts from public and private centers of different parts of Brasil. Several key questions concerning clinical indications, outcomes and technological requirements for hypofractionation were discussed and voted. For each question, consensus was reached if there was an agreement of at least 75% of the panel members. RESULTS: The recommendations are described in this article. CONCLUSION: This initiative will assist Brazilian radiation oncologists and medical physicists to safely treat localized prostate cancer patients with hypofractionation.


Subject(s)
Prostatic Neoplasms , Radiotherapy, Intensity-Modulated , Brazil , Humans , Male , Prospective Studies , Prostatic Neoplasms/radiotherapy , Radiation Dose Hypofractionation , Treatment Outcome
20.
Rev. Assoc. Med. Bras. (1992) ; 67(1): 7-18, Jan. 2021. tab
Article in English | LILACS | ID: biblio-1287777

ABSTRACT

SUMMARY OBJECTIVE: Several prospective randomized trials have shown that hypofractionation has the same efficacy and safety as the conventional fractionation in the treatment of localized prostate cancer. There are many benefits of hypofractionation, including a more convenient schedule for the patients and better use of resources, which is especially important in low- and middle-income countries like Brasil. Based on these data, the Brazilian Society of Radiotherapy (Sociedade Brasileira de Radioterapia) organized this consensus to guide and support the use of hypofractionated radiotherapy for localized prostate cancer in Brasil. METHODS: The relevant literature regarding moderate hypofractionation (mHypo) and ultra-hypofractionation (uHypo) was reviewed and discussed by a group of experts from public and private centers of different parts of Brasil. Several key questions concerning clinical indications, outcomes and technological requirements for hypofractionation were discussed and voted. For each question, consensus was reached if there was an agreement of at least 75% of the panel members. RESULTS: The recommendations are described in this article. CONCLUSION: This initiative will assist Brazilian radiation oncologists and medical physicists to safely treat localized prostate cancer patients with hypofractionation.


Subject(s)
Prostatic Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated , Brazil , Prospective Studies , Treatment Outcome , Radiation Dose Hypofractionation
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