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OBJECTIVES: To assess the diagnostic performance of ultrasound (US), x-rays, and microscopic analysis of synovial fluid (SF) for calcium pyrophosphate dihydrate crystal deposition disease (CPPD) using histology as a reference standard. METHODS: We enrolled consecutive patients with osteoarthritis waiting to undergo knee replacement surgery. Each patient underwent US of the knee, focusing on menisci and the hyaline cartilage, the day before surgery. During surgery, SF, menisci and condyles were retrieved and examined microscopically. For the meniscus and cartilage microscopic analysis, 8 samples were collected from each specimen and knee radiographs, performed up to 3 months before surgery, were also assessed. A dichotomous score was given for the presence/absence of CPP for each method. Microscopic findings of the specimens were considered the reference standard. All the procedures followed were in accordance with the ethical standards of the local responsible committee. RESULTS: 42 patients (14 males) were enrolled. All patients underwent US, 34 had eligible radiographs and 32 had SF analysis. 25 patients (59.5%) were positive for CPP at US, 15 (44.1%) at X-ray and 14 (43.7%) at SF. Sensitivity and specificity values were 96% and 87% for US, 75% and 93% for radiography and 77% and 100% for SF respectively. There were no statistically significant differences between the diagnostic performance across single tests. CONCLUSIONS: US proved to be at least as accurate as SF analysis for the diagnosis of CPPD. US, which is feasible and harmless, could be considered the first exam of choice for CPPD diagnosis.
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Pirofosfato de Cálcio/análise , Condrocalcinose/diagnóstico , Líquido Sinovial/química , Idoso , Idoso de 80 Anos ou mais , Condrocalcinose/diagnóstico por imagem , Cristalização , Feminino , Humanos , Masculino , Radiografia , Sensibilidade e Especificidade , UltrassonografiaRESUMO
Clodronate is the father of bisphosphonates. For over three decades it has been subject of study in biological and clinical areas, proving to be an extremely interesting molecule from different points of view. It has been the first drug for osteoporosis that can be administered pulsatorily (once every 15 days or once a week). This, along with good tolerability, has been the first cause of its success, when there were no solid data in literature about its antifracture efficacy. There are three published studies that prove its antifracture effect: two by McCloskey published in 2004 and 2007 on BMR, and our study about fracture prevention in corticosteroids OP. In these studies a dose of 800 mg/day orally administered or 100 mg/week I.M. was used, and they are basically the same if you consider that clodronate absorption, orally administered, is on average 1.9%. However, a series of works where higher doses were used (1600 mg orally administered) with greater effectiveness on bone mass, especially in higher risk populations, lead us to consider the use of 200 mg i.m. formulation. First of all, we proved densitometric equivalence of 200 mg i.m./14 days and 100 mg i.m./week in a first study; then, in a second study, we proved a greater densitometric efficacy of 200 mg/week compared to 100 mg/week, clearer at femoral level, where the drug had not proven to prevent femoral fracture because of inadequate bone mass increase at that level. Moreover, as for ibandronate case, monthly dose was doubled compared to pivotal trial, in order to maximize the effects on femoral bone mass and therefore prevent femoral fractures. Consequently, on the basis of the risk envelope, whether it is identified according to BMD and the presence of one risk factor at least or more correctly identified through risk chart (FRAX or DeFRA), you can put forward a differential use of 100 mg i.m. and 200 mg i.m., weekly, "off-label" or every 14 days, adjusting doses in relation to fracture risk and painful symptoms gravity, as well as improving its ease of use and therefore assist compliance. Common experience and clinical and biological works have proved that clodronate has an analgesic effect that can be increased by doubling the doses. The analgesic effect is present not only with patients with fractures, but also with patients suffering from osteoarthritis or arthritis. Therefore, the drug would fit well in the therapeutic program of rheumatic patient, also because of its symptomatic effects. Clodronate at small doses (2 mg) could also have protective effects on cartilage (introduction of intra-articular formulation is expected) and at 10-100 fold higher doses it has certainly anti-inflammatory effects and more specifically antimacrophage and anticytokine effects (IL-1, IL-6, TNFalpha, PGE). These effects are amplified by putting clodronate in monolayer liposomes. This drug, therefore, has to be considered as adjuvant in arthritis therapy, whose origin can be linked to a strong osteoclastic activation caused by an increase of cytokines and the RANKL/OPG relationship. It is clear that clodronate can work on cytokine at first and on osteoclastic effector in the end. The drug has been used "off-label" for decades intravenously in complex regional pain syndrome (CRPS type 1) in relation to schemes that change according to different Authors and according to cumulative doses ranging from 3 to 5 g. The introduction on the market of the 200 mg i.m. formulation could allow to get more practical but equally effective schemes. For example, we used this scheme: 200 mg/day for 10 days and then 200 mg every other day for 20 days (cumulative dose of 4 g in a month). Said scheme can be repeated in the following months in particular cases. Results, as for efficacy and lack of relapses, show that clodronate is the leader drug for this syndrome. In recent years, relationship between costs and benefits has started to matter, especially after the creation of some algorithms, such as FRAX, that let us choose patients with a higher fracture risk in 10 years, and after pharmaceutic-economic models that let us calculate FRAX intervention threshold, on the basis of drug price and monitoring, antifracture efficacy, quality of life and how much a community can or wants to spend. In this respect, a sub-analysis of McCloskey's study on people over the age of 75, conducted on 3974 subjects, shows that clodronate is more efficient with patients with a higher fracture risk, calculated according to FRAX. Furthermore, another study by McCloskey revealed that, for a 100-pound/year drug (very similar to clodronate), 'cost effective' intervention threshold is about 7-10%. In conclusion, clodronate prevents fractures, decrease osteo-articular pain, is easy to handle, tolerable and had a great cost/benefit relationship.
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OBJECTIVE: Our study's objective was to assess the incidence trends and healthcare resource utilization of hospitalizations for Tick-Borne Encephalitis (TBE) and associated costs in Italy in order to improve public awareness and preventive measures. METHODS: This retrospective observational study was based on the Italian Ministry of Health's Hospital Discharge Record (HDR) database. Data were gathered across Italy from 2015 to 2019, selecting hospitalizations with ICD-9 code 063 related to TBE, both in primary and secondary diagnoses. For each year, we collected the following variables: number of hospitalizations, hospitalization rate, mortality rate, mean length of hospital stay, hospital ward, and cost of hospitalization. RESULTS: There were a total of 237 hospitalizations from 2015 to 2019; 62 % of those were male. The lowest number of TBE hospitalizations was in 2015 (21 cases, corresponding to 0.35 per million inhabitants), the highest in 2019 (64 cases, 1.04 per million inhabitants). The summer months saw a greater than average number of hospitalizations. For the years analyzed, the cumulative number of cases peaked in June (54 cases), July (46 cases), and August (35 cases). There were only two deaths registered in our study sample. TBE cases were mostly localized in the North-Eastern regions of Italy. TBE incidence during the study period in the most affected areas were: Autonomous Province of Trento, ranging from 11.2 to 42.3 per million inhabitants, Autonomous Province of South Tyrol, from 0 to 21.1 per million inhabitants, and Veneto Region, from 2.6 to 4.5 per million inhabitants. In the study period, the average length of hospital stay was largely stable ranging from 10.6 days to 12.8 days, with related costs ranging from 5,813.7 to 7,352.5 . CONCLUSIONS: According to our data, the majority of TBE hospitalizations occur in North-East Italy with an increasing trend over the analyzed period. Even though Italy has fewer TBE cases than other neighboring European countries, the health and economic impact can be high in the affected areas.
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BACKGROUND: Respiratory syncytial virus (RSV) affects 60-80% of children below 1 year and it's the first cause of acute bronchiolitis. The aim of this study was to assess the trend and characteristics of hospitalizations for RSV infections in Italy. METHODS: This is a retrospective study based on the Italian Hospital Discharge Record (HDR) database. We analysed HDRs from June 2015 to May 2019, considering two groups of infants: Group 1 had a confirmed diagnosis of RSV; Group 2 had a diagnosis of acute bronchiolitis not RSV-coded. RESULTS: There were 67,746 overall hospitalizations (40.1% Group 1, and 59.9% Group 2). Hospitalization rate increased for Group 1 from 125 to 178 per 10,000 infants (+ 42.4%), and for Group 2 from 210 to 234 per 10,000 (+ 11.4%). The mean hospitalization length was 6.3 days in Group 1, longer than Group 2 (+ 1.0 day). A further analysis revealed that infants with heart disease or born premature had longer mean hospital stay compared to infants without risk factors (10.7 days versus 6.1 days, p < 0.0001; 34.0 days versus 6.1 days, p < 0.0001, respectively). Group 1 required more critical care (oxygen therapy and/or mechanical ventilation) than Group 2. We found that, in proportion to hospital admissions in pediatric and general hospitals, RSV was more frequently diagnosed in the first ones. The mean hospitalization cost increased for Group 1 (from 2,483 to 2,617) and Group 2 (from 2,007 to 2,180). CONCLUSIONS: Our results confirmed that RSV pulmonary disease in infants is seasonal and often requires hospitalization. Our study suggested that RSV is responsible for an increasing hospitalization rate and related costs during the study period.
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Hospitalização , Infecções por Vírus Respiratório Sincicial , Humanos , Itália/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/terapia , Estudos Retrospectivos , Lactente , Hospitalização/estatística & dados numéricos , Feminino , Masculino , Recém-Nascido , Tempo de Internação/estatística & dados numéricosRESUMO
OBJECTIVE: To assess the extent of calcium pyrophosphate dihydrate (CPP) crystal deposition and the distribution of affected sites, using ultrasonography (US), in patients affected by CPP deposition disease (CPPD). PATIENTS AND METHODS: 42 consecutive patients affected by definite CPPD according to the McCarty criteria were enrolled in the study. All patients underwent an US examination of metacarpophalangeal joints of II, III, IV and V fingers of both hands, wrists and knees, Achilles' tendons and plantar fascia looking for CPP deposits. A dichotomous score for presence/absence of CPP and a semiquantitative score for extent of deposits (0-3: 0, absent; 1, 1-2 spots; 2, more than two spots covering <50% of the structure; 3, deposits covering >50% of the structure) were assigned to each site examined. A site distribution score (total number of affected sites) was then calculated as well as an extent score equal to the sum of the extent scores of all sites. RESULTS: The mean involvement in our patients was 4.7 sites (SD±1.7, range 2-8 sites). The knee was the most affected, site (41 of 42) followed by the wrist (at least one in 37 patients) the Achilles' tendons (23 patients), plantar fascia (11 patients) and metacarpophalangeal joints (four patients). The highest mean values of the extent score were in the menisci, followed by the hyaline cartilage of the femoral condyles and the entheses. CONCLUSIONS: The deposition of CPP crystals involves at least two sites with a mean of four sites involved in most patients affected by CPPD and is therefore an oligoarticular or polyarticular disease.
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Condrocalcinose/diagnóstico por imagem , Articulações/diagnóstico por imagem , Tendão do Calcâneo/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Fáscia/diagnóstico por imagem , Feminino , Pé/diagnóstico por imagem , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Articulação Metacarpofalângica/diagnóstico por imagem , Pessoa de Meia-Idade , Ultrassonografia , Articulação do Punho/diagnóstico por imagemRESUMO
OBJECTIVES: We aimed to measure the fractal dimension on x-ray images and ultrasonographic parameters of the os calcis of bone from 4 districts in osteoporotic patients and in control subjects, in order to test the hypothesis that ultrasonographic parameters correlate to the fractal dimension obtained on x-ray images. METHODS: Fractal analysis on radiological images from 4 bone districts (proximal femur, calcaneus, metacarpus and 3rd phalanx) was performed in a study comparing ultrasonographic evaluation of the os calcis in severe osteoporotic patients and in control cases. We studied 86 x-ray-views from patients with severe reduction of ultrasound Stiffness Index and in healthy women. Ultrasound measurements of left os calcis were performed using the Lunar Achilles-Plus instrument. Fractal analysis was performed using the box-counting method. RESULTS: In healthy subjects, fractal dimension, D, measure of structural complexity, resulted close to the topological dimension (no fractal structure), TD, in femur (1.99±0.03)and phalanx (1.96±0.03), D differed significantly from TD in calcaneus (D=1.90±0.02; p<0.001) and metacarpus (D=1.89±0.03, p<0.001). In osteoporotic subjects, in calcaneus and metacarpus, D was higher (1.94±0.03, 1.93±0.03, respectively) than in healthy subjects (1.90±0.02, 1.89±0.02, respectively, p<0.01). In all the subjects, fractal dimension and ultrasound broadband attenuation T-score correlated significantly in calcaneus and metacarpus (p<0.03 and p<0.02, respectively). CONCLUSIONS: Parameters based on a combination of ultrasonic examination and fractal analysis on radiographic images may add useful structural information regarding the patients' skeleton using non invasive procedures.
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Osso e Ossos/diagnóstico por imagem , Fractais , Osteoporose/diagnóstico por imagem , Idoso , Calcâneo/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Fêmur/diagnóstico por imagem , Falanges dos Dedos da Mão/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Ossos Metacarpais/diagnóstico por imagem , Pessoa de Meia-Idade , Radiografia , UltrassonografiaRESUMO
PURPOSE: Ultrasonography (US) has been demonstrated to be an important tool in the diagnosis of calcium pyrophosphate (CPP) crystal deposition disease. The aim of our study was to individuate and describe possible pitfalls in US detection of such deposits in menisci. PATIENTS AND METHODS: We enrolled all patients waiting to undergo knee replacement surgery due to osteoarthritis, for one-month period. Each patient underwent US examination of the knee, focusing on the menisci. After surgery, the menisci were examined by US, macroscopically and microscopically, using the microscopic analysis as the gold standard for CPP deposition. RESULTS: 11 menisci of 6 patients have been studied. Ex vivo examination of menisci performed better in CPP identification than in vivo examination. The possible reasons of misinterpretation or misdiagnosis of the in vivo exam were identified and are extensively described in the paper. Also a new sign of CPP crystal deposits was found. CONCLUSIONS: This study permitted to highlight some difficulties in CPP crystal detection by US in menisci. Further studies are needed to define completely US CPP crystal aspect and to improve the sensibility and specificity of US in CPP deposition diagnosis.
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Pirofosfato de Cálcio/análise , Meniscos Tibiais/química , Idoso , Idoso de 80 Anos ou mais , Cristalização , Feminino , Humanos , Masculino , Meniscos Tibiais/diagnóstico por imagem , Pessoa de Meia-Idade , UltrassonografiaRESUMO
Tofacitinib is an oral Janus kinase (JAK) inhibitor indicated for the treatment of rheumatoid arthritis (RA). The efficacy and safety/tolerability of tofacitinib have been extensively evaluated as monotherapy and combination therapy in multiple, randomised, multicentre studies in patients with RA. Tofacitinib as monotherapy (as first- and second-line treatment) or as combination with methotrexate (MTX) or other csDMARDs as second- and third-line treatment is effective and generally well tolerated in patients with RA. This article focuses on recent real-world evidence investigating the effectiveness, treatment persistence and safety/tolerability of tofacitinib in patients with RA. With this purpose, a literature review was conducted from April 2018 up to October 2020 for the effectiveness, persistence and safety of tofacitinib for the treatment of RA, primarily focusing on real-world studies. These retrospective and prospective and observational studies demonstrate the effectiveness of tofacitinib, thus supporting pivotal data from the clinical trial programme. Treatment persistence was generally comparable to that of biologic disease-modifying anti-rheumatic drugs. Safety findings in these observational studies were consistent with the known safety profile of the approved dose of 5 mg twice daily.
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Peroxisomes are important in plant physiological functions and stress responses. Through the production of reactive oxygen and nitrogen species (ROS and RNS), and antioxidant defense enzymes, peroxisomes control cellular redox homeostasis. Peroxin (PEX) proteins, such as PEX7 and PEX5, recognize peroxisome targeting signals (PTS1/PTS2) important for transporting proteins from cytosol to peroxisomal matrix. pex7-1 mutant displays reduced PTS2 protein import and altered peroxisomal metabolism. In this research we analyzed the role of PEX7 in the Arabidopsis thaliana root system exposed to 30 or 60 µM CdSO4. Cd uptake and translocation, indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) levels, and reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels and catalase activity were analyzed in pex7-1 mutant primary and lateral roots in comparison with the wild type (wt). The peroxisomal defect due to PEX7 mutation did not reduce Cd-uptake but reduced its translocation to the shoot and the root cell peroxisomal signal detected by 8-(4-Nitrophenyl) Bodipy (N-BODIPY) probe. The trend of nitric oxide (NO) and peroxynitrite in pex7-1 roots, exposed/not exposed to Cd, was as in wt, with the higher Cd-concentration inducing higher levels of these RNS. By contrast, PEX7 mutation caused changes in Cd-induced hydrogen peroxide (H2O2) and superoxide anion (O2â-) levels in the roots, delaying ROS-scavenging. Results show that PEX7 is involved in counteracting Cd toxicity in Arabidopsis root system by controlling ROS metabolism and affecting auxin levels. These results add further information to the important role of peroxisomes in plant responses to Cd.
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Chronic inflammation, such as that present in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), leads to aberrations in bone remodeling, which is mediated by several signaling pathways, including the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. In this light, pro-inflammatory cytokines are now clearly implicated in these processes as they can perturb normal bone remodeling through their action on osteoclasts and osteoblasts at both intra- and extra-articular skeletal sites. As a selective inhibitor of JAK1 and JAK3, tofacitinib has the potential to play a role in the management of rheumatic diseases such as RA and PsA. Preclinical studies have demonstrated that tofacitinib can inhibit disturbed osteoclastogenesis in RA, which suggests that targeting the JAK-STAT pathway may help limit bone erosion. Evidence from clinical trials with tofacitinib in RA and PsA is encouraging, as tofacitinib treatment has been shown to decrease articular bone erosion. In this review, the authors summarize current knowledge on the relationship between the immune system and the skeleton before examining the involvement of JAK-STAT signaling in bone homeostasis as well as the available preclinical and clinical evidence on the benefits of tofacitinib on prevention of bone involvement in RA and PsA.Key Points⢠Chronic inflammation in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) leads to disturbances in bone remodeling⢠Bone remodeling is mediated by several signaling pathways, including the JAK-STAT pathway⢠Tofacitinib, a selective inhibitor of JAK1 and JAK3, is active in RA and PsA and may help limit systemic bone loss through inhibiting disturbed osteoclastogenesis⢠Clinical trials show that tofacitinib reduces articular bone erosion.
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Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Remodelação Óssea/efeitos dos fármacos , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Humanos , Sistema Imunitário/efeitos dos fármacos , Janus Quinases/antagonistas & inibidores , Fatores de Transcrição STAT/efeitos dos fármacos , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To evaluate the pattern of prescription and maintenance over time of concomitant methotrexate (MTX), and its impact on a 2-year clinical response in a cohort of rheumatoid arthritis (RA) patients treated with a first-line tumor necrosis factor alpha inhibitor (TNFi). PATIENTS AND METHODS: The study population included all RA patients receiving adalimumab or etanercept a as first-line biologic drug, extracted from a local registry. Enrolled patients were stratified into 3 subgroups according to baseline concomitant MTX: no MTX, low-dose MTX (≤10 mg/wk), and high-dose MTX (≥12.5 mg/wk). The 2-year persistence of the initial MTX regimen was computed by the Kaplan-Meier method, and a Cox proportional hazard model was developed to examine potential predictors of MTX withdrawal/change of dosage. European League Against Rheumatism remission and good-to-moderate response were evaluated according to baseline MTX regimen and MTX maintenance over time. RESULTS: A total of 330 patients (163 treated with adalimumab and 167 with etanercept) were included; 141 were prescribed TNFi without MTX and 112 received low-dose and 77 high-dose concomitant MTX. Male sex, younger age, and shorter mean disease duration were predictors of high-dose MTX use. Among MTX users (76.2% parenteral and 23.8% oral), initial MTX dose persisted over time in 79.9% at 1 year and 70.2% at 2 years. Fifty-one patients (27%) underwent MTX dose de-escalation/discontinuation because of intolerance/adverse events. The 2-year EULAR remission rate was higher in the patients receiving and maintaining high-dose MTX than in those receiving low-dose or no MTX (46.2% vs 29.5% and 23.4%, respectively; p=0.009). The same was true for good-to-moderate response rate (71.2% vs 52.6% and 50.4%, respectively; p=0.031). CONCLUSION: In a real-life setting, about one-third of RA patients treated with TNFis experienced dose reduction/discontinuation of concomitant MTX because of intolerance/adverse events over a 2-year follow-up period. Initial high-dose MTX and its maintenance over time are associated with better 2-year clinical response.
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Adalimumab/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Etanercepte/uso terapêutico , Metotrexato/uso terapêutico , Adalimumab/administração & dosagem , Relação Dose-Resposta a Droga , Etanercepte/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de TempoAssuntos
Pirofosfato de Cálcio/metabolismo , Doenças das Cartilagens/diagnóstico , Condrocalcinose/diagnóstico , Meniscos Tibiais/patologia , Idoso , Idoso de 80 Anos ou mais , Doenças das Cartilagens/diagnóstico por imagem , Doenças das Cartilagens/metabolismo , Células Cultivadas , Condrocalcinose/diagnóstico por imagem , Condrocalcinose/metabolismo , Feminino , Humanos , Masculino , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/metabolismo , Meniscos Tibiais/cirurgia , Pessoa de Meia-Idade , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Projetos Piloto , Valor Preditivo dos Testes , UltrassonografiaRESUMO
The study objective was to report treatment with an interleukin (IL)-1 receptor antagonist, anakinra, in patients with multiorgan Behcet's disease (BD). Comparison of clinical manifestations, previous treatments, markers of inflammation, concomitant medications, treatment regimen modifications, relapses, and adverse events before and during anakinra administration among patients with BD were evaluated. Nine BD patients (mean age 34.55 ± 16.30 years) refractory to tumor necrosis factor blockers and standardized therapies are reported in our survey. Their mean age at disease onset was 25 ± 13.88 years and their overall disease duration was 9.55 ± 5.33 years. All patients were positive for the HLA-B51 allele. Within 1 or 2 weeks following the initiation of anakinra, eight out of nine patients promptly responded, and most of them were maintained on 100 mg of daily anakinra with low doses of prednisone. However, most patients experienced a relapse in one or more clinical manifestations over time (mean time to relapse 29 ± 21.65 weeks), and only one patient remained completely under control on anakinra monotherapy. Despite a relapse in one or more disease manifestations, treatment was continued in most patients for a mean period of 13.75 ± 6.49 months. No serious adverse events occurred. Eight out of nine refractory BD patients showed a prompt improvement after starting anakinra, supporting the concept that IL-1 plays a pathological role in this disease. Nevertheless, after several months, most patients experienced a relapse. It remains unclear whether increasing the dose of anakinra would have prevented the reoccurrence of disease activity.
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Antirreumáticos/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Resistência a Medicamentos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Adulto , Alelos , Biomarcadores/sangue , Criança , Feminino , Antígeno HLA-B51/genética , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento , Uveíte/tratamento farmacológico , Adulto JovemRESUMO
Background. Bone damage in rheumatoid arthritis (RA) and in psoriatic arthritis (PsA) includes an accelerated bone mineral density (BMD) reduction. The objective was to evaluate BMD variations of the metacarpophalangeal joints (MCPs) in patients starting treatment with methotrexate (MTX) or etanercept. Methods. Patients affected by RA or PsA with hand joints involvement and with moderate or high disease activity, were enrolled in this study. All patients underwent clinical examination, laboratory exams, and a DXA scan of the most affected hand, as assessed with an ultrasound examination at the baseline, at the time of enrolment and after 1, 3, 6, and 12 months. Patients non-responders to MTX received combination therapy, while patients with no previous treatment initiated MTX. Results. 22 patients were enrolled. In both RA and PsA groups, BMD increased independently of the treatment. However, in the patients affected by RA, a slight BMD decrease was observed at the last checkup. Globally, the BMD variations of the MCPs were strongly correlated with the disease activity. At the reduction of DAS28, the scores corresponded an increase of BMD. Conclusions. MCPs BMD is inversely correlated to disease activity. BMD increase seems to be correlated with the response to treatment and not with the drug itself.
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BACKGROUND: Clodronate is a bisphosphonate used for the treatment of postmenopausal osteoporosis and all conditions characterized by excess bone resorption. We have previously reported that intramuscular (IM) therapy with clodronate at a dose of 100 mg/week displays significant effects on bone mineral density (BMD) although a plateau effect is observed after 1 year of treatment. Previous reports indicate that the densitometric effects of bisphosphonates directly correlate with the drug dosage and suggest that using IM clodronate at doses higher than 100 mg/week may result in improved efficacy. However, to the best of our knowledge, this has never been proved. OBJECTIVE: The primary endpoint of the study was the effect on BMD of IM clodronate 100 mg once weekly or 100 mg twice weekly in patients with postmenopausal osteoporosis. The incidence of non-traumatic vertebral fractures and adverse events was also reported. METHODS: The present study was a randomized, open-label, parallel-group trial conducted between January 2007 and December 2009 in the Osteoporosis and Osteoarticular Instrumental Diagnosis Centre (University of Siena, Siena, Italy). The study involved 60 women, aged 57-78 years, with a history of postmenopausal osteoporosis for more than 5 years. Patients were randomized to receive IM clodronate 100 mg once weekly (Group A, 30 patients) or 100 mg twice weekly (Group B, 30 patients), for 2 years. RESULTS: Significant increases compared with baseline in BMD were observed for both groups at 1 and 2 years, with significantly higher increases for Group B compared with Group A. Group B displayed a BMD increase (± SD) at the lumbar spine of +4.0 % (± 2.1) and +5.9 % (± 2.0) at 1 and 2 year(s), respectively, compared with +2.8 % (± 1.7) and +3.5 % (± 2.2), respectively, observed for Group A. Similarly, Group B showed better performance compared with Group A for BMD increase at the femoral neck, with an observed increase of +3.5 % (± 1.7) and +5.4 % (± 1.8) at 1 and 2 year(s), respectively, compared with a change of +2.3 % (± 1.9) and +2.5 % (± 1.9), respectively, registered in Group A. Consistently, the BMD increase measured at the total femur was significantly higher for Group B [+3.4 % (± 1.9) and +4.9 % (± 2.1) at years 1 and 2, respectively] compared with Group A [+1.6 % (± 0.9) and +2.4 % (± 1.9) at years 1 and 2, respectively]. When the change in BMD from year 1 to year 2 was compared, a significant increase of BMD was seen in Group B in all the analysed regions, contrary to that observed for Group A where a plateau effect resulted in no significant change from year 1 to year 2. Three non-traumatic vertebral fractures occurred during the study: two in Group A and one in Group B. CONCLUSION: The present study indicates the superior performance of IM clodronate 200 mg weekly (100 mg twice weekly) compared with 100 mg once weekly in BMD in women with postmenopausal osteoporosis. This work demonstrated that administration of twice the drug dosage in a week significantly improved the efficacy of the treatment without inducing serious adverse events. Therefore, IM clodronate 200 mg weekly may be considered a valid therapeutic choice for the treatment of postmenopausal osteoporosis.